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2,300 | 20,620,163 | Overall , social cognition was more strongly associated with community functioning than neurocognition , with the strongest associations being between theory of mind and functional outcomes . | The current systematic review and meta- analysis provides an extended and comprehensive overview of the associations between neurocognitive and social cognitive functioning and different types of functional outcome . | OBJECTIVE The relationship between cognition and outcome in people with schizophrenia has been established in studies that , for the most part , examined chronic patients and were cross-sectional in design . The purpose of this study was to analyze the relationships between neurocognitive variables assessed at illness onset and functional outcome in a longitudinal design . An additional area of interest was whether the severity of negative symptoms would predict outcome independently from neurocognitive variables or whether there would be an overlap in their predictive power . METHOD The authors administered a comprehensive cognitive battery and clinical assessment s to 99 subjects who were in their first episode of illness and analyzed the relationship of cognition and symptom severity at intake with community outcome after an average follow-up period of 7 years . RESULTS Verbal memory , processing speed and attention , and the severity of negative symptoms at intake were related to subsequent outcome . Global psychosocial functioning was predicted by negative symptoms and attention . Verbal memory was the significant predictor of the degree of impairment in recreational activities . Impairment in relationships was predicted by negative symptoms and memory , whereas attention and negative symptoms were predictive of work performance . There was an overlap in the variance in outcome explained by cognitive variables and negative symptoms . CONCLUSIONS Verbal memory and processing speed and attention are potential targets for psychosocial interventions to improve outcome . Results from cross-sectional or chronic patient studies do not necessarily correspond to the findings of this prospect i ve first-episode study in which cognition appears to explain less of the variance in outcome Neurocognitive deficits are believed to be important predictors of functional outcome in chronic psychotic disorders , but few supporting studies have utilized prospect i ve design s and adequate control . The aim of this study was to estimate the relative influence of symptoms and neurocognitive deficits on the development of social behavior skills in a cohort of individuals with schizophrenia or schizoaffective disorder recovering from acute symptom exacerbations . Forty-six individuals were recruited upon discharge from an inpatient unit and completed assessment s of symptoms , neurocognitive function , and social behavior at 3-month intervals for 1 year . Correlational analyses and r and om regression models were used to model social behavioral capacities longitudinally . Social behavior improved modestly ( 10 % improvements in ratings ) over the follow-up period for the group as a whole . Disorganized and negative symptoms , as well as neurocognitive deficits in short-term and working memory predicted changes in social behavior over time . Individuals with better working memory function showed significantly greater abilities to recover social behavior skills , whereas those with working memory deficits showed no functional improvement over time . Both symptoms and neurocognitive deficits are important determinants of functional outcome in schizophrenia . It is proposed that clinicians should consider neurocognitive thresholds for treatment response when developing rehabilitation plans Social functioning deficits ( e.g. , social skill , community functioning ) are a core feature of schizophrenia . These deficits are only minimally improved via the frontline treatments for schizophrenia ( e.g. medication , social skills training , cognitive-behavioral therapy ) . Social cognition is a promising treatment target in this regard as it may be more strongly related to social functioning outcomes than traditional neurocognitive domains [ Couture , S. , Penn , D.L. , Roberts , D.L. , 2006 . The functional significance of social cognition in schizophrenia : a review . Schizophrenia Bulletin ( Suppl . 1 ) , S-44 - 63 ] . Social cognition and interaction training ( SCIT ) is a 20-week , manualized , group treatment design ed to improve social functioning in schizophrenia by way of improved social cognition . This article reports preliminary data from a quasi-experimental study comparing SCIT + treatment as usual ( TAU ; n=20 ) to TAU alone ( n=11 ) among out patients . Results using analysis of variance ( ANOVA ) suggest SCIT-related improvements in emotion perception and social skill UNLABELLED Biosocial models are preeminent in the study of schizophrenia , yet there has been little empirical testing of these models . OBJECTIVE This study provided the first test of a biosocial causal model of functional outcome in schizophrenia , using neurocognition , social cognition , social competence and social support as predictors of both global and specific domains of functional outcome . METHOD The design used baseline variables to predict both concurrent functional status and prospect i ve 12-month functional outcome . Subjects were recruited upon admission to outpatient community-based psychosocial rehabilitation programs shown in previous studies to be effective in improving functional outcomes . 139 individuals diagnosed with schizophrenia or schizoaffective disorder participated in the study ; 100 participants completed the 12-month assessment s. Face-to-face interviews assessed neurocognitive functioning ( with five neuropsychological measures ) , social cognition ( as perception of emotion ) , social competence , social support , and functional outcome which consisted of items covering the domains of social , independent living , and work functioning . RESULTS Path analysis modeling showed that the proposed biosocial models had strong fit with the data , for both concurrent and 12-month global functional outcomes , with fit indices ranging from .95 to .98 . The model explained 21 % of the variance in concurrent global functional outcome , and 14 % of the variance in 12-month prospect i ve outcome . CONCLUSIONS The support for this model was strong , and it has implication s for underst and ing the causal factors related to functional outcome , as well as for intervention strategies for improving functional outcomes in schizophrenia Deficits in the ability to perceive facial and vocal emotion expression are common in schizophrenia . However , relatively little is known about how such deficits might affect functional outcomes . This prospect i ve study examined cross-sectional and longitudinal relationships between perception of emotion and aspects of psychosocial functioning , including family relationships , social relationships , work functioning , and independent living/self-care in 94 clinical ly stabilized schizophrenia out patients from five community-based rehabilitation programs . Emotion perception ( facial emotion , voice emotion , and affect perception ) and psychosocial outcome ( Strauss and Carpenter Outcome Scale and Role Functioning Scale ) were assessed at baseline and after 12 months of psychosocial rehabilitation . Significant associations were found between perception of emotion and work functioning/independent living both cross-sectionally and prospect ively over the 12 months . Causal explanatory models suggested that perception of emotion might cause work functioning/independent living outcome over 1 year . The results remained significant when conceptual disorganization was statistically controlled . We did not find differences between men and women in the correlations between emotion perception and work functioning/independent living . Associations between social functioning/family relationships and perception of emotion were not significant . These findings suggest that emotion processing is a key determinant of work functioning/independent living for individuals with serious mental illness The purpose of this study was to assess how neurocognition and social cognition were associated with initial functional level and with rates of functional change in intensive community-based psychosocial rehabilitation interventions that have been shown to yield significant functional change for individuals diagnosed with schizophrenia . We also examined how service intensity was associated with rates of change and whether it served as a moderator of the relationship between functional change and both neurocognition and social cognition . The sample consisted of 125 individuals diagnosed with schizophrenia or schizoaffective disorder who were recruited upon admission to 1 of 4 community-based psychosocial rehabilitation facilities and were followed prospect ively for 12 months . One hundred and two subjects completed the 12-month protocol . The findings suggested that ( i ) the initial level of psychosocial functioning was related to both social cognition and neurocognition at baseline , ( ii ) when significant rehabilitative change occurs , higher neurocognition and social cognition scores at baseline predicted higher rates of functional change over the subsequent 12 months , ( iii ) greater service intensity was related to higher rates of improvement in functional outcome over time , and ( iv ) service intensity moderated the relationship between neurocognition and initial functional level and moderated the relationship between social cognition and the rates of functional change at a trend level . These findings have relevance to our underst and ing of the heterogeneity in functional rehabilitative outcomes , to our underst and ing of the conditions of rehabilitative change and for the design of psychosocial interventions in the community This study examined whether frontal-system impairments in schizophrenia occur independently of one another and whether they have distinct implication s for information processing , symptom severity , and adaptive functioning . We assessed 26 medication-free schizophrenic out patients and 18 normal control subjects on eight frontally mediated tasks , semantic information processing , IQ , the BPRS , and long-term psychosocial adaptation . Schizophrenic subjects showed three types of deficits , which were uncorrelated with one another : ( 1 ) Executive dysfunction ( inflexible problem solving ) was related to decreased use of expectancy during controlled semantic priming , lower intelligence , more severe negative symptoms and stereotyped mannerisms . ( 2 ) Disinhibition of responses ( to irrelevant stimuli ) was associated with increased automatic priming , a trend for more severe hallucinations , and was unrelated to intelligence . ( 3 ) Motor dyscoordination ( inaccurate , dysfluent motor sequencing ) was not related to semantic processing , intelligence , or symptoms . Furthermore , all three impairments were unrelated to generalized slowness , age , sex , illness length , or pre-washout neuroleptic dose . Two deficits accounted for aspects of long-term psychosocial adaptation , even after statistical correction for IQ : Executive dysfunction was associated with younger illness onset , poor purpose fulness and planning , impaired social relations , and lower global functioning . Motor dyscoordination was associated with poor treatment outcome and restricted educational advancement . Furthermore , executive and motor deficits interacted significantly ; subjects who had both deficits showed the least favorable treatment outcome . These findings are neither consistent with generalized impairment nor with a unitary ' frontal syndrome ' in schizophrenia . They provide preliminary evidence for at least three frontal-system deficits ( dorsolateral , orbital , and premotor ) , which are dissociable from one another , can occur without general intellectual impairment , and have distinct implication s for long-term adaptive functioning The purpose of this cross-sectional study was to examine the relationships between neurocognitive deficits and quality of life for patient with schizophrenia . Fifty-seven schizophrenic out patients ( 38 men and 19 women ) were assessed for neurocognitive deficits using the Wisconsin Card Sorting Test ( WCST ) and all patients completed the PCASEE ( P = physical , C = cognitive , A = affective , S = social , E = economic-social , and E = ego functions ) question naire to assess their quality of life . We assessed psychiatric symptoms using the Schedule for the Assessment of Positive Symptoms ( SAPS ) and the Schedule for the Assessment of Negative Symptoms ( SANS ) . We rated the Abnormal Involuntary Movement Scale ( AIMS ) for extrapyramidal side effects . Pearson correlational analyses were conducted to assess the relationships among measures of quality of life , neurocognitive functioning , symptoms , and extrapyramidal side effects . There were significant relationships among the total score of the PCASEE question naire and the SANS total score and the AIMS total score ( P<.001 ) . Small but significant associations were found among the total score of the PCASEE question naire and the SAPS total score and a number of nonperseverative errors ( P<.05 ) . Negative symptoms and extrapyramidal side effects in schizophrenia appear to have direct impact on the patient 's perceived quality of life BACKGROUND Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability . Attempts at rehabilitation have had circumscribed effects on cognition , without concurrent improvement in broad aspects of behavior and adjustment . OBJECTIVE To determine the differential effects of cognitive enhancement therapy ( a recovery-phase intervention ) on cognition and behavior compared with state-of-the-art enriched supportive therapy . DESIGN A 2-year , r and omized controlled trial with neuropsychological and behavioral assessment s completed at baseline and at 12 and 24 months . SETTING An outpatient research clinic housed in a medical center 's comprehensive care service for patients with severe mental illness . PATIENTS A total of 121 symptomatically stable , non-substance-abusing but cognitively disabled and chronically ill patients with schizophrenia or schizoaffective disorder . INTERVENTIONS Cognitive enhancement therapy is a multidimensional , developmental approach that integrates computer-assisted training in neurocognition with social cognitive group exercises . Enriched supportive therapy fosters illness management through applied coping strategies and education . MAIN OUTCOME MEASURES Six highly reliable summary measures --Processing Speed , Neurocognition , Cognitive Style , Social Cognition , Social Adjustment and Symptoms -- were tested using analysis of covariance and linear trend analysis . RESULTS At 12 months , robust cognitive enhancement therapy effects were observed on the Neurocognition and Processing Speed composites ( P<.003 ) , with marginal effects observed on the behavioral composites . By 24 months , differential cognitive enhancement therapy effects were again observed for the 2 neuropsychological composites and for Cognitive Style ( P=.001 ) , Social Cognition ( P=.001 ) , and Social Adjustment ( P=.01 ) . As expected , no differences were observed on the residual Symptoms composite . Effects were unrelated to the type of antipsychotic medication received . Enriched supportive therapy also demonstrated statistically significant within-group effect sizes , suggesting that supportive psychotherapy can also have positive , although more modest , effects on cognitive deficits . CONCLUSION Many cognitive deficits and related behaviors of patients with stable schizophrenia are improved when sufficient exposure to relevant rehabilitation is provided Social cognitive deficits are promising treatment targets for new interventions to improve functional outcome in schizophrenia . A few preliminary studies of in patients support the feasibility of improving social cognition through psychosocial interventions . This clinical trial evaluated a new 12-session social cognitive skills training program design ed to address four aspects of social cognition ( affect perception , social perception , attributional style , Theory of Mind ) in out patients with psychosis , a population for whom such interventions will likely be very useful . Thirty-one clinical ly stabilized out patients were r and omly assigned to a social cognition skills training intervention or a time-matched control condition ( illness self-management and relapse prevention skills training ) , and completed pre- and post-treatment assessment s of social cognition , neurocognition , and symptoms . The social cognition group demonstrated a large , significant improvement in facial affect perception , which was not present in the control group . This improvement was independent of changes in basic neurocognitive functioning or symptoms . Results support the efficacy of a social cognitive intervention for community-dwelling out patients and encourage further development of this treatment approach to achieve broader improvements in social cognition and generalization of treatment gains Neurocognition is moderately to severely impaired in patients with schizophrenia . However , the factor structure of the various neurocognitive deficits , the relationship with symptoms and other variables , and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia . An ‘ all-comer ’ approach to cognition is needed , as provided by the baseline assessment of an unprecedented number of patients in the CATIE ( Clinical Antipsychotic Trials of Intervention Effectiveness ) schizophrenia trial . From academic sites and treatment providers representative of the community , 1493 patients with chronic schizophrenia were entered into the study , including those with medical comorbidity and substance abuse . Eleven neurocognitive tests were administered , result ing in 24 individual scores reduced to nine neurocognitive outcome measures , five domain scores and a composite score . Despite minimal screening procedures , 91.2 % of patients provided meaningful neurocognitive data . Exploratory principal components analysis yielded one factor accounting for 45 % of the test variance . Confirmatory factor analysis showed that a single-factor model comprised of five domain scores was the best fit . The correlations among the factors were medium to high , and scores on individual factors were very highly correlated with the single composite score . Neurocognitive deficits were modestly correlated with negative symptom severity ( r=0.13–0.27 ) , but correlations with positive symptom severity were near zero ( r<0.08 ) . Even in an ‘ all-comer ’ clinical trial , neurocognitive deficits can be assessed in the overwhelming majority of patients , and the severity of impairment is similar to meta-analytic estimates . Multiple analyses suggested that a broad cognitive deficit characterizes this sample . These deficits are modestly related to negative symptoms and essentially independent of positive symptom severity |
2,301 | 29,292,650 | RESULTS Evidence exists to show that rLH supplementation seems to have added value for pregnancy achievement in women with poor ovarian response and in women ≥35 years of age employing the GnRH agonist protocol , while the evidence is still debatable when the GnRH antagonist is administered .
In the general infertile population , rLH supplementation does not have added value in the GnRH-antagonist cycles while the evidence is still controversial when the GnRH agonist is employed .
An accurate definition of the LH threshold in GnRH analogue treated cycles may contribute to the discussion of which subgroups of women may benefit from adjuvant rLH therapy | OBJECTIVE To look into current evidence exploring the added value of rLH supplementation to rFSH in GnRH analogues cycles , to identify groups of women that still have no evidence for adjuvant rLH therapy and to discuss ways that may advance research on this topic . | The study evaluated the proportion of patients whose pituitary gl and s respond with a sharp decrease in luteinizing hormone ( LH ) levels when exposed to a conventional dose of 0.25 mg gonadotropin releasing hormone ( GnRH ) antagonist in a prospect i ve , single-center , non-r and omized , proof-of-concept study . Fifty women eligible for in vitro fertilization ( IVF ) received recFSH ( Gonal-F ) from day 2 or 3 of menstrual period . Basal estradiol , progesterone , and LH were measured on the same day and 4 - 5 days later–-immediately before GnRH antagonist 0.25 mg administration , and 24 hours after its administration . Responders were defined as “ normal ” if 24 hours after the first GnRH antagonist injection , LH level was ≥50 % of the pre-injection level and as “ over-suppressed ” if it was < 50 % of the pre-injection level . Twelve patients ( 26 % of the total ) were “ over-suppressed ” with a mean LH level of 37 % of the level 24 hours earlier . These patients also demonstrated a significant decrease in estradiol rise during the first 24 hours after initial antagonist administration . This effect was reversed for the rest of the stimulation period during which recLH ( Luveris , 150 IU/day ) was added to the “ over-suppressed . ” If proven advantageous in terms of pregnancy rate , this approach to individualized treatment would be easy to implement . Trial registration : Clinical Trials.gov Identifier : NCT01936077 BACKGROUND The role of LH in sensitizing antral follicles to FSH is unclear . LH is required for normal hormone production and normal oocyte and embryo development , but follicular responses to LH may depend upon the stage of development . Potential roles at the early follicular phase were explored in a clinical setting by employing a sequential approach to stimulation by recombinant human ( r-h ) LH followed by r-hFSH in women who were profoundly down-regulated by depo GnRH agonist . METHODS We employed a multi-centre , prospect i ve , r and omized approach . Women ( n = 146 ) were treated in a long course high-dose GnRH agonist ( Decapeptyl , 4.2 mg s.c . ) protocol and were r and omized to receive r-hLH ( Luveris , 300 IU/day ) for a fixed 7 days , or no r-hLH treatment . This was followed by a st and ard r-hFSH stimulation regime ( Gonal-F , 150 IU/day ) . Ultrasound and hormone assessment s of responses were measured at the start of r-hLH treatment , on FSH stimulation Days 0 and 8 and at the time of HCG administration . RESULTS The LH treatment was associated with increased small antral follicles prior to FSH stimulation ( P = 0.007 ) , and an increased yield of normally fertilized ( 2 PN ) embryos ( P = 0.03 ) . There was no influence of the r-hLH pretreatment upon hormone profiles or ultrasound assessment s during the FSH phase . Anti-mullerian hormone increased in both groups during the week prior to FSH stimulation ( P = 0.002 ) . CONCLUSIONS This sequential approach to the use of r-hLH in st and ard IVF showed a possible modest clinical benefit . The results support other recent work exploring up-regulated and rogen drive upon follicular metabolism indicating that clinical benefit may be obtainable after further practical explorations of the concept The impact of suppressed concentrations of circulating luteinizing hormone ( LH ) during ovarian stimulation on the outcome of in-vitro fertilization or intracytoplasmic sperm injection treatment in 200 consecutive , normogonadotrophic women ( couples ) was analysed retrospectively . A st and ard stimulation protocol with mid-luteal gonadotrophin-releasing hormone ( GnRH ) agonist down-regulation and ovarian stimulation with recombinant follicle stimulating hormone ( FSH ) was used in all cases . Blood was sample d from each woman on stimulation days 1 and 8 for analysis of oestradiol and LH in serum . A threshold value of serum LH of 0.5 IU/l on stimulation day 8 ( S8 ) was chosen to discriminate between women with low or ' normal ' LH concentrations . Low concentrations of LH on S8 ( < 0.5 IU/l ) were found in 49 % ( 98/200 ) of the women . This group of women was comparable with the normal LH group with regard to pre-treatment clinical parameters , and to the parameters characterizing the stimulation protocol with the exception of serum oestradiol concentration , which on S8 was significantly lower than in the normal LH group ( P < 0.001 ) . The proportion of positive pregnancy tests was similar in the two groups ( 30 % versus 34 % per started cycle ) , but the final clinical treatment outcome was significantly different , with a five-fold higher risk of early pregnancy loss ( 45 % versus 9 % ; P < 0.005 ) in the low LH group and consequently a significantly poorer chance of delivery than in the normal LH group . It is concluded that a substantial proportion of normogonadotrophic women treated with GnRH agonist down-regulation in combination with FSH , devoid of LH activity , experience LH suppression , which compromises the treatment outcome . Whether these women would benefit from supplementation with recombinant LH or human menopausal gonadotrophin during ovarian stimulation , remains to be proven in the future by prospect i ve r and omized trials A multicentre , open-label , r and omized study of the gonadotrophin-releasing hormone ( GnRH ) antagonist ganirelix ( Orgalutran((R))/Antagon((TM ) ) ) was performed in women undergoing ovarian stimulation with recombinant FSH ( rFSH : Puregon((R ) ) ) . The study was design ed as a non-inferiority study using a long protocol of buserelin ( intranasal ) and rFSH as a reference treatment . A total of 730 subjects was r and omized in a treatment ratio of 2:1 ( ganirelix : buserelin ) using an interactive voice response system which stratified for age , type of infertility and planned fertilization procedure [ IVF or intracytoplasmic sperm injection ( ICSI ) ] . The median duration of GnRH analogue treatment was 5 days in the ganirelix group and 26 days in the buserelin group , whereas the median total rFSH dose was 1500 IU and 1800 IU respectively . In addition , in the ganirelix group the mean duration of stimulation was 1 day shorter . During ganirelix treatment the incidence of LH rises ( LH > /=10 IU/l ) was 2.8 % versus 1.3 % during rFSH stimulation in the buserelin group . On the day of triggering ovulation by human chorionic gonadotrophin ( HCG ) , the mean number of follicles > /=11 mm diameter was 10.7 and 11.8 , and the median serum oestradiol concentrations were 1190 pg/ml and 1700 pg/ml in the ganirelix and buserelin groups respectively . The mean number of oocytes per retrieval was 9.1 and 10.4 respectively , whereas the mean number of good quality embryos was 3.3 and 3.5 respectively . The fertilization rate was equal in both groups ( 62.1 % ) , and the same mean number of embryos ( 2.2 ) was replaced . The mean implantation rates were 15.7 % and 21.8 % , and the ongoing pregnancy rates per attempt were 20.3 % and 25.7 % in the ganirelix and buserelin groups respectively . Evaluation of all safety data indicated that the ganirelix regimen was safe and well tolerated . The overall incidence of ovarian hyperstimulation syndrome was 2.4 % in the ganirelix group and 5.9 % in the reference group . The results of this study support a safe , short and convenient treatment regimen of ganirelix , result ing in a good clinical outcome for patients undergoing ovarian stimulation for IVF or ICSI Although the fundamental significance of both LH and FSH for adequate ovarian folliculogenesis and steroidogenesis has been extensively discussed , the clinical implication of recombinant ( r ) LH to rFSH for ovarian stimulation employing the GnRH antagonist protocol remains to be eluci date d. The aim of this prospect i ve r and omized controlled study was to explore whether rLH supplementation to rFSH following GnRH antagonist has an added value to the late follicular ovarian steroidogenesis in the advanced reproductive aged women OBJECTIVE To analyze the impact of LH administration on cycle outcome in ovarian stimulation with GnRH antagonists . DESIGN R and omized , open-label , controlled trial performed in two age subgroups . Recombinant ( r ) FSH versus rFSH + rLH administration was compared . SETTING University-affiliated private infertility clinic . PATIENT(S ) Up to 35 years old ( n = 380 ) and aged 36 to 39 years ( n = 340 ) , undergoing their first or second IVF cycle . INTERVENTION(S ) Recombinant LH administration since stimulation day 1 . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate . RESULT ( S ) In the young population , implantation rates were similar : 27.8 % versus 28.6 % , odds ratio ( OR ) 1.03 ( 95 % confidence interval [ CI ] 0.73 - 1.47 ) , as was the ongoing pregnancy rate per started cycle : 37.4 % versus 37.4 % , OR 1.0 ( 95 % CI 0.66 - 1.52 ) . In older patients , the implantation rate was significantly higher in the rFSH + rLH group : 26.7 % versus 18.6 % , OR 1.56 ( 95 % CI 1.04 - 2.33 ) . Ongoing pregnancy rates per started cycle were 33.5 % versus 25.3 % , OR 1.49 ( 95 % CI 0.93 - 2.38 ) . CONCLUSION ( S ) Recombinant LH administration significantly increased the implantation rate in patients aged 36 to 39 years . A clinical ly relevant better ongoing pregnancy rate per started cycle was observed , although the difference was not statistically significant . Patients younger than 36 years do not obtain any benefit from rLH administration OBJECTIVE To evaluate clinical and endocrinological effects of intranasal ( IN ) vs. subcutaneous ( SC ) GnRH-a for pituitary down-regulation combined with hMG vs. rFSH . DESIGN Prospect i ve , r and omized study . SETTING University hospital , IVF unit . PATIENT(S ) Three hundred seventy-nine normogonadotropic women eligible for IVF or ICSI . INTERVENTION(S ) R and omization to intranasal ( IN ) or SC GnRH-a and to hMG or rFSH . MAIN OUTCOME MEASURE(S ) Oocytes retrieved , embryos developed , clinical pregnancy , and delivery rates . Serum hormone concentrations on stimulation days 1 ( S1 ) and 8 ( S8 ) , and oocyte pick-up ( OPU ) day . RESULT ( S ) After r and omization , four groups were formed : IN/hMG ( n = 100 ) , IN/FSH ( n = 98 ) , SC/hMG ( n = 89 ) , and SC/FSH ( n = 92 ) . Mean number of oocytes retrieved and of transferable and transferred embryos were similar in the four groups . Clinical pregnancy rate per started cycle was significantly higher in the IN/HMG group than in the SC/FSH group ( P<.05 ) and was intermediate in the two remaining groups . Se-LH on S8 in the two SC groups was significantly lower than in the two IN groups . Se-E2 on S8 in the SC/FSH group was significantly lower than in the other three groups . CONCLUSION ( S ) The clinical and endocrinological outcome in IVF and ICSI-treated normogonadotropic women is significantly influenced by mode of down-regulation as well as gonadotropin formulation OBJECTIVE To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies . DESIGN Prospect i ve r and omized study . SETTING SISMER fertility unit . PATIENT(S ) Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were r and omized into three groups : group A ( n = 54 ) received an increased dosage of FSH ; group B ( n = 54 ) was administered recombinant LH in addition to the increased dose of FSH ; group C ( n = 22 ) was given additional FSH and LH using hMG as a combined drug . Fifty-four age-matched women with no need to increase the FSH dose were included as a control group ( D ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Implantation and live birth rate per started cycles . RESULT ( S ) In group B , the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response . The live birth rate was similar in groups B and D but was half as high in groups A and C. CONCLUSION ( S ) Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that , in turn , could affect oocyte competence . Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos Purpose To explore serum endocrine dynamics , specifically LH levels , following rLH supplementation to rFSH following GnRH-antagonist treatment in the advance reproductive age . Methods Women were prospect ively and similarly treated employing rFSH and the flexible GnRH-antagonist protocol , while rLH was supplemented only to the study group . Serum FSH , LH , E2 , and P were evaluated throughout the follicular phase . Three strategies were a priori planned to examine endocrine dynamics among women enrolled . Results While serum LH drop were similar before GnRH-antagonist stimulation , it dropped more times in the control group compared to the study group . Among women receiving rFSH only , serum LH levels dropped ≤2 , ≤1 and ≤0.5 mIU/mL in 71.4 , 46.4 , and 28.6 % of cases , while this occurred only in 38.7 % ( P = 0.01 ) , 6.5 % ( P = 0.0004 ) and 3.2 % ( P = 0.007 ) of women receiving combined rFSH and rLH treatment , respectively . The same trend was found when serum LH dropped in at least two occasions following the GnRH-antagonist administration . Conversely , serum LH diagrams throughout the follicular phase did not differ between the two groups . Furthermore , individual area under the curve values of LH , E2 , and P was similar between the two groups following GnRH-antagonist initiation . Conclusions Different strategies to explore LH dynamics following the GnRH-antagonist administration have result ed in diverse results , implying the need for a consensus definition of LH threshold for adequate folliculogenesis and steroidogenesis . Such action would pave the way for underst and ing which groups of patients may benefit from rLH supplementation A total of 346 women with normal ovulatory function was stimulated with human menopausal gonadotrophins ( HMG ) to attain ovarian stimulation for IVF or intracytoplasmic sperm injection ( ICSI ) . Stimulation with HMG started on cycle day 2 or 3 . After 6 days of stimulation , Cetrorelix in its minimum effective multiple dose of 0 . 25 mg/day , was administered daily until induction of ovulation . In total , 333 patients ( 96.2 % ) reached the day of HCG administration , and 324 ( 93.6 % ) underwent oocyte retrieval . A mean of 25.2 ampoules of HMG was applied for a mean of 10.4 days . Cetrorelix was administered for a mean time lapse of 5.7 days . The mean normal fertilization rate was 60 % in the IVF group and 59 % in the ICSI group . Seventy pregnancies were attained , reflecting an ongoing clinical pregnancy rate of 24 % per transfer . The ongoing clinical implantation rate was 11.4 % . Only three cases of raised luteinizing hormone ( LH ) ( > /=10 IU/l ) with increased progesterone secretion ( > /=1 ng/ml ) were observed after initiation of Cetrorelix administration , reflecting an incidence of premature luteinization of 0.9 % . The abortion rate was 17 % . The incidence of severe ovarian hyperstimulation syndrome ( World Health Organization grade III ) was as low as 0.6 % STUDY QUESTION Does the addition of exogenous LH to an IVF/ICSI stimulation protocol with recombinant FSH ( r-FSH ) and a GnRH antagonist improve the ovarian response and pregnancy rates in women of 35 years and older ? SUMMARY ANSWER Supplementation of LH during the second half of the follicular phase has no effect on pregnancy rates , implantation rates or on ovarian response in women of 35 years and older undergoing GnRH antagonist IVF/ICSI cycles . WHAT IS KNOWN ALREADY In IVF/ICSI stimulation protocol s GnRH agonists or antagonists are administered to prevent a premature pituitary LH surge , which can have a detrimental effect on the IVF/ICSI procedure . In effect , GnRH analogues cause the levels of both gonadotrophins to drop . In order to allow follicle growth FSH is administered exogenously , whereas LH is usually not supplemented . Although GnRH analogues prevent LH surges , there is evidence that , particularly in older women , administration of GnRH analogues may cause endogenous LH levels to decrease excessively . Several studies have been performed to investigate whether the addition of recombinant LH ( r-LH ) to r-FSH improves cycle outcome . Only a few studies have analysed this issue in the GnRH antagonist protocol and the results of these trials obtained in older women ( > 35 years old ) are conflicting . STUDY DESIGN , SIZE , DURATION A multicentre RCT was performed between 2004 and 2010 in 253 couples who were undergoing IVF or ICSI . Women were 35 years or older and received ovarian stimulation in a protocol with r-FSH ( Gonal-F 225 IU/day ) starting from cycle day 3 and GnRH antagonist ( Cetrotide 0.25 mg/day ) from stimulation day 6 . R and omization took place on stimulation day 6 to receive both r-FSH and r-LH ( Luveris 150 IU/day ) or continue with FSH alone . R and omization for r-LH supplementation was performed central ly by serially numbered , opaque , sealed envelopes , stratified by centre . PARTICIPANTS / MATERIAL S , SETTING , METHODS Of 253 subjects r and omized , 125 received both r-FSH and r-LH and 128 received r-FSH only . Patients were recruited from the Division of Reproductive Medicine of the Obstetrics and Gynaecology department of four hospitals in the Netherl and s. MAIN RESULTS AND THE ROLE OF CHANCE There were no demographic or clinical differences between the groups . The intention-to-treat analysis revealed that of those receiving both r-FSH and r-LH , 35 ( 28.0 % ) had a clinical pregnancy , compared with 38 ( 29.7 % ) receiving only r-FSH ( mean difference -1.5 % ; 95 % confidence interval ( CI ) -9.4 to 12.7 , P = 0.9 ) . Ongoing pregnancy rates were 25 ( 20 % ) versus 28 ( 21.9 % ) ( mean difference -1.9 % ; 95 % CI -8.2 to 11.9 , P = 0.9 ) and implantation rates 18.8 versus 20.7 % ( mean difference -1.9 % ; 95 % CI -8.0 to 11.7 , P = 0.6 ) in the ' r-FSH and r-LH ' and ' r-FSH only ' groups respectively . LIMITATIONS , REASONS FOR CAUTION A limitation of our study is its early closure . This was done because the interim analysis after r and omization of 250 patients indicated no benefit in any aspect of the experiment . WIDER IMPLICATION S OF THE FINDINGS Given previous data , including a Cochrane review , and our own results the evidence indicates that LH supplementation has no benefit on ongoing pregnancy rates in women of 35 years or older . STUDY FUNDING /COMPETING INTEREST(S ) Merck Serono Netherl and s , an affiliate of Merck Serono SA- Geneva , an affiliate of Merck KGaA , Darmstadt , Germany has donated the r-LH ( Luveris ( ® ) ) . No conflict of interest to declare . TRIAL REGISTRATION NUMBER The trial was registered in the Dutch trial register ( IS RCT N10841210 ) BACKGROUND The effect of early- and mid-follicular LH concentrations on the ovarian response and pregnancy outcomes was evaluated in women receiving pituitary down-regulation with a GnRH agonist and ovarian stimulation with recombinant FSH ( rFSH ) during IVF/ICSI treatment . METHODS Blood sample s were collected prospect ively from 701 cycles ( 560 patients ) of assisted reproduction and analysed retrospectively . On the basis of LH concentrations on stimulation day 7/8 , the patients were divided into two groups : LH<1.2 IU/l ( n=179 ) and LH > or=1.2 IU/l ( n=522 ) . Cycle outcomes were also compared on the basis of a ratio of mid- to early-follicular LH concentrations ( < or=0.5 , n=210 ; > 0.5 , n=491 ) . RESULTS Patients with low LH concentrations were found to have a significant reduction in the late-follicular estradiol concentrations ( P<0.001 ) , the number of oocytes retrieved ( P<0.01 ) and the number of usable embryos ( P<0.01 ) , and they required significantly more rFSH ( 430 IU difference , P<0.01 ) . These differences did not translate into a significant change in live birth rates . Conversely , a ratio of < or=0.5 mid- to early-follicular LH concentrations ( a reduction of > or=50 % ) was associated with a significant reduction in live birth rates per embryo transfer and per cycle started ( 27.3 versus 19.0 % , P<0.05 and 22.2 versus 15.8 % , P<0.05 , respectively ) . CONCLUSIONS Low mid-follicular levels of LH have a significant impact on ovarian response but not on live birth rates . A fall in LH level of > or=50 % from the early- to mid-follicular phase result ed in a lower live birth rate BACKGROUND The effect of LH levels on stimulation day 8 on ovarian response and pregnancy outcome were evaluated in women receiving pituitary down-regulation with GnRH agonists ( 0.8 mg Suprefact ) s.c . daily until pituitary down-regulation and 0.4 mg/day during ovarian stimulation ) and ovarian stimulation with recombinant FSH . METHODS Blood sample s were prospect ively collected from a total of 207 normal women undergoing assisted reproduction and analysed retrospectively . Based on LH levels on stimulation day 8 patients were divided into four groups : < 0.5 , 0.51 - 1.0 , 1.01 - 1.5 , > 1.51 IU/l . RESULTS Estradiol levels on day 8 and estradiol per oocyte retrieved showed a highly significant correlation with LH concentrations on day 8 . The total consumption of exogenous FSH and duration of gonadotrophin stimulation was inversely related to LH levels on day 8 ( P < 0.002 ) . The frequencies of fertilization and clinical pregnancies were superior in the two middle groups . Only 12 % of the patients showed LH levels < 0.5 IU/l , which , however , may be explained by the particular mode and doses of GnRH agonist used . CONCLUSIONS Circulating levels of LH on day 8 have a significant impact on ovarian response and pregnancy outcome . LH should neither be too high nor too low . The mode of administration and the dose of the GnRH agonist used may determine the number of women who experience LH levels below 0.5 IU/l STUDY QUESTION Does luteinizing hormone ( LH ) supplementation improve live birth rate after in vitro fertilization ( IVF ) in patients aged ≥35 years receiving a gonadotrophin-releasing hormone ( GnRH ) antagonist protocol ? SUMMARY ANSWER There was no difference in live birth rate with use of LH during IVF in patients aged ≥35 years undergoing IVF treatment using a GnRH antagonist protocol . WHAT IS KNOWN ALREADY Use of GnRH analogues as part of a controlled ovarian hyperstimulation protocol during IVF treatment cycles decreases the amount of LH available to developing follicles . The role of LH supplementation for improving outcomes in patients undergoing controlled ovarian hyperstimulation as part of assisted reproduction treatments , particularly those involving a GnRH antagonist protocol , is unclear . It has been suggested that higher risk patients ( e.g. age ≥35 years , poor ovarian reserve ) may benefit from LH supplementation . STUDY DESIGN , SIZE , DURATION This single-centre , r and omized controlled trial was conducted from 1 October 2012 to 30 June 2014 . A total of 240 women aged ≥35 years undergoing IVF received ovarian stimulation using a GnRH antagonist protocol , with recombinant follicle-stimulating hormone ( r-FSH ; Gonal-F ( ® ) ) starting from cycle day 2 or 3 . GnRH antagonist ( Cetrotide ( ® ) ) was administered on Day 5 of r-FSH administration . On Day 6 , patients in the LH supplementation group were switched to r-FSH/r-LH ( Pergoveris ( ® ) ) 150/75 IU/day . R and omization to study treatments was performed in blocks of 4 via a computer-generated r and om number list . PARTICIPANTS / MATERIAL S , SETTING , METHODS Of the 240 patients r and omized to treatment , 120 received r-FSH/r-LH and 120 received r-FSH . Patients were recruited from the IVFAS , An Sinh Hospital , Ho Chi Minh City , Vietnam . MAIN RESULTS AND THE ROLE OF CHANCE Live birth rate did not differ significantly ( P > 0.05 ) between r-FSH/r-LH and r-FSH recipients ( 16.7 versus 17.5 % ; between-group difference 0.8 , 95 % confidence interval [ CI ] -9.5 , 11.2 ) . In addition , there were no significant differences between the r-FSH/r-LH and r-FSH groups with respect to the number of oocytes retrieved , implantation rate , miscarriage rate and clinical pregnancy rate . LIMITATIONS , REASONS FOR CAUTION The open-label design could have introduced bias , and the relatively small sample size may have allowed detection of only the most common adverse events . In addition , the study was likely to be underpowered based on differences between the response rate assumptions used in the sample size calculation and the actual response rate during the study . WIDER IMPLICATION S OF THE FINDINGS The results of this study found no additional benefit from adding LH supplementation to ovarian stimulation with a GnRH antagonist protocol in women aged ≥35 years , and add to the body of evidence in this area . However , findings across studies are still inconsistent and additional research is needed before any clear recommendations for clinical practice can be made . STUDY FUNDING /COMPETING INTERESTS This study was supported by the Research Center for Genetics and Reproductive Health , School of Medicine , Vietnam National University HCMC . The authors state that they have no financial or commercial conflicts of interest . TRIAL REGISTRATION NUMBER The trial was registered with clinical trials.gov ( NCT02244866 ) The association between endogenous LH concentrations during ovarian stimulation in a gonadotrophin-releasing hormone ( GnRH ) antagonist protocol and pregnancy likelihood was examined in a large combined analysis of individualized patient data obtained after treatment with recombinant FSH and a GnRH antagonist prior to IVF/intracytoplasmic sperm injection . Data from 1764 patients from six r and omized controlled trials were pooled for retrospective analysis . Ongoing pregnancy and miscarriage rates for patients stratified by LH percentiles were assessed . Patients in the lowest LH quartile ( < P25 ) were younger with a higher predicted ovarian reserve and response compared with patients in the highest quartile ( > P75 ) . With adjustment for identified predictive factors of pregnancy , estimated odds ratios ( 95 % confidence interval ) for ongoing pregnancy for LH categories < P25 versus ≥ P25 , > P75 versus ≤ P75 and < P25 versus > P75 were 0.96 ( 0.75 - 1.22 ) , 1.13 ( 0.88 - 1.45 ) and 0.89 ( 0.66 - 1.21 ) on stimulation day 8 , and 0.96 ( 0.76 - 1.21 ) , 1.03 ( 0.82 - 1.30 ) and 0.95 ( 0.72 - 1.26 ) on the day of human chorionic gonadotrophin , respectively . No significant differences in pregnancy or miscarriage rates between the LH categories were observed . Endogenous LH concentrations have no association with the likelihood of ongoing pregnancy in women undergoing ovarian stimulation using a recombinant FSH/GnRH antagonist protocol |
2,302 | 18,665,189 | A high GL , but not a high GI , diet is positively associated with the risk of endometrial cancer , particularly among obese women | Long-term consumption of a high glycaemic index ( GI ) or glycaemic load ( GL ) diet may lead to chronic hyperinsulinaemia , which is a potential risk factor for cancer .
To date , many studies have examined the association between GI , GL and cancer risk , although results have been inconsistent , therefore our objective was to conduct a systematic review of the literature . | BACKGROUND Growth in normal and malignant tissues has been linked to hyperinsulinemia and insulin-like growth factors ( IGFs ) . We hypothesized that IGF and IGF-binding protein ( IGFBP ) responses may be acutely affected by differences in the glycemic index ( GI ) of foods . OBJECTIVE We compared the postpr and ial responses of IGFs and IGFBP to 2 foods of similar macronutrient composition but with greatly different GIs-pearled barley ( GI : 25 ) and instant mashed potato ( GI : 85 ) . DESIGN Ten young lean subjects consumed 50-g carbohydrate portions of the 2 foods or water ( extended fast ) in r and om order after an overnight fast . Capillary blood was collected at regular intervals over 4 h for measurement of blood glucose , insulin , and components of the IGF system . RESULTS Serum IGFBP-1 declined markedly after both meals , but the mean ( + /-SEM ) change at 4 h was significantly ( P < 0.01 ) more prolonged after the low-GI meal ( -55 + /- 20 ng/mL ) than after the high-GI meal ( -13 + /- 15 ng/mL ) . Conversely , the change in serum IGFBP-3 concentration at 4 h was significantly ( P < 0.05 ) higher after the low-GI meal ( 251 + /- 102 ng/mL ) than after the high-GI meal ( -110 + /- 96 ng/mL ) ; the same pattern was observed at 2 h. Changes in IGFBP-2 , free IGF-1 , and total IGF-1 responses were minimal and did not differ significantly from those during the 4-h fast . CONCLUSION Acute changes in IGFBP-3 after low-GI and high-GI foods may provide a biologic mechanism linking cell multiplication with greater consumption of high-GI carbohydrates Reliable tables of glycemic index ( GI ) compiled from the scientific literature are instrumental in improving the quality of research examining the relation between GI , glycemic load , and health . The GI has proven to be a more useful nutritional concept than is the chemical classification of carbohydrate ( as simple or complex , as sugars or starches , or as available or unavailable ) , permitting new insights into the relation between the physiologic effects of carbohydrate-rich foods and health . Several prospect i ve observational studies have shown that the chronic consumption of a diet with a high glycemic load ( GI x dietary carbohydrate content ) is independently associated with an increased risk of developing type 2 diabetes , cardiovascular disease , and certain cancers . This revised table contains almost 3 times the number of foods listed in the original table ( first published in this Journal in 1995 ) and contains nearly 1300 data entries derived from published and unpublished verified sources , representing > 750 different types of foods tested with the use of st and ard methods . The revised table also lists the glycemic load associated with the consumption of specified serving sizes of different foods The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content To evaluate the role of nutritional factors in the etiology of endometrial cancer , we performed a case-cohort analysis using data from women enrolled in the National Breast Screening Study in Canada from 1980 to 1985 . For this analysis , a subcohort was constructed by selecting a 10 % r and om sample from the 56,837 women in the dietary cohort . Cases were the 221 women diagnosed with incident adenocarcinoma of the endometrium during follow-up to December 31 , 1993 and ascertained by record linkage to the Canadian Cancer Data base . Information on usual diet at enrolment and other epidemiological variables was collected by means of self-administered question naires . Hazard ratios were obtained from proportional hazards regression models , with estimation of robust st and ard errors . We found a strong association of endometrial cancer with body mass index > 25 kg/m2 ( hazard ratio 2.72 , 95 % CI : 2.06–3.50 ) . Endometrial cancer risk was not associated significantly with intakes of total energy , carbohydrates , proteins , total fat and major fatty acids , total dietary fiber and various types of fibers , vitamin C , E and A , folic acid , β-carotene , lutein , or cryptoxanthin . Some decrease in risk was noted with relatively high intakes of saturated fat , animal fat or lycopene . The associations observed in the study were independent of total energy intake and most non-dietary risk factors . The study suggests that dietary intakes of energy and most major nutrients are not related to the risk of endometrial cancer among Canadian women The quantification of errors inherent in methods of measuring dietary intake has been h and icapped by the absence of independent markers for testing their validity . The doubly labeled water technique permits a precise measure of energy expenditure in free-living persons . Because energy expenditure must equal energy intake in population s in energy balance , this technique may be used to vali date the assessment of energy intake . A series of studies demonstrated good agreement between mean energy intake and mean energy expenditure when food intake was recorded by observers or when it was self-reported by normal-weight , self-selected , highly motivated volunteer subjects using weighed records . However , in r and omly recruited men and women , energy intake by weighed records was 82 % and 81 % , of energy expenditure , respectively , indicating underestimation of habitual intake . Men and women in the lowest third of reported intake recorded energy expenditure of only 69 % and 61 % , respectively . Reported intake of obese and previously obese women was only 73 % and 64 % of expenditure , whether measured by weighed record or by diet history , confirming suspicions that these subjects misrepresented their intake . Acceptable weighed records were obtained from 7- and 9-year-olds whereas 15- and 18-year-olds underestimated intake . Diet histories taken from the same children tended to overestimate intake . These studies suggest that , ideally , all dietary studies should include independent measures of validity Insulin-like growth factor (IGF)–related hormones and binding proteins ( IGFBP ) have been implicated in cancer risk . Specifically , two recent , small prospect i ve studies reported a significant positive association between IGF-I and ovarian cancer risk among women diagnosed before age 55 years . Therefore , we examined whether plasma concentrations of IGF-I , IGFBP-3 , and IGFBP-2 were associated with risk of epithelial ovarian cancer in a nested case-control study using data from three prospect i ve cohorts : the Nurses ' Health Study ( NHS ) , NHSII , and the Women 's Health Study ( WHS ) . The present study had 222 cases ( 159 from NHS/NHSII and 63 from WHS ) and 599 controls ( matching ratio , 1:3 for NHS/NHSII and 1:2 for WHS ) . Women ranged in age from 34 to 73 years ( mean , 56 years ) . The relative risk ( RR ) comparing the top versus bottom quartile of IGF-I was 0.56 ( 95 % confidence interval , 0.32 - 0.97 ; Ptrend = 0.14 ) . The risk did not differ by age at diagnosis ( comparable RR for age < 55 years at diagnosis , 0.70 ; RR for age ≥55 years at diagnosis , 0.52 ) . We did not observe any association between IGFBP-3 , IGFBP-2 , and the ratio of IGF-I to either binding protein and ovarian cancer risk . Overall , our results do not support a positive association between IGF-related proteins and ovarian cancer risk . ( Cancer Epidemiol Biomarkers Prev 2007;16(8):1691–5 We conducted a case‐control study nested within the European Prospect i ve Investigation into Cancer and Nutrition , to examine the associations between prediagnostic serum concentrations of C‐peptide , insulin‐like growth factor binding protein (IGFBP)‐1 and IGFBP‐2 , and endometrial cancer risk . Among pre‐ and post‐menopausal women , who were not currently using exogenous hormones , 286 women developed incident endometrial cancer during an average 5.1 years follow‐up . Using risk set sampling , 555 matched control subjects were selected . In conditional logistic regression models adjusted for matching factors only , endometrial cancer risk increased with increasing serum levels of C‐peptide ( relative risks ( RR ) for the top vs. bottom quartile = 2.13 [ 95 % confidence interval ( CI ) 1.33–3.41 ] , ptrend = 0.001 , and decreasing serum levels of IGFBP‐2 ( RR for the top vs. bottom quartile = 0.56 [ 95 % CI 0.35–0.90 ] , ptrend = 0.03 , but was not significantly associated with IGFBP‐1 levels ( RR for the top vs. bottom quartile = 0.76 [ 95 % CI 0.47–1.21 ] , ptrend = 0.25 ) . In BMI ‐adjusted models , only the C‐peptide association remained marginally statistically significant ( RR for the top vs. bottom quartile = 1.56 [ 95 % CI 0.94–2.57 ] , ptrend = 0.05 for C‐peptide ; 0.84 [ 95 % CI 0.50–1.40 ] , ptrend = 0.74 for IGFBP‐2 ; and 1.08 [ 95 % CI 0.65–1.78 ] , ptrend = 0.86 for IGFBP‐1 levels ) . These associations were stronger among nonfasting women ( ≤≤6 hr since last meal ; 63 % of subjects ) but were not evident among fasting women , although the interactions were not statistically significant . The C‐peptide‐risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women ( RR for the top vs. bottom quartile = 1.28 [ 95 % CI 0.67–2.45 ] , ptrend = 0.42 . Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer . © 2007 Wiley‐Liss , The applicability of the glycaemic index ( GI ) in the context of mixed meals and diets is still debatable . The objective of the present study was to investigate the predictability of measured GI in composite breakfast meals when calculated from table values , and to develop prediction equations using meal components . Furthermore , we aim ed to study the relationship between GI and insulinaemic index ( II ) . The study was a r and omised cross-over meal test including twenty-eight healthy young men . Thirteen breakfast meals and a reference meal were tested . All meals contained 50 g available carbohydrate , but differed considerably in energy and macronutrient composition . Venous blood was sample d for 2 h and analysed for glucose and insulin . Prediction equations were made by regression analysis . No association was found between predicted and measured GI . The meal content of energy and fat was inversely associated with GI ( R(2 ) 0.93 and 0.88 , respectively ; P<0.001 ) . Carbohydrate content ( expressed as percentage of energy ) was positively related to GI ( R(2 ) 0.80 ; P<0.001 ) . Using multivariate analysis the GI of meals was best predicted by fat and protein contents ( R(2 ) 0.93 ; P<0.001 ) . There was no association between GI and II . In conclusion , the present results show that the GI of mixed meals calculated by table values does not predict the measured GI and furthermore that carbohydrates do not play the most important role for GI in mixed breakfast meals . Our prediction models show that the GI of mixed meals is more strongly correlated either with fat and protein content , or with energy content , than with carbohydrate content alone . Furthermore , GI was not correlated with II BACKGROUND There is some evidence that plasma insulin levels might influence ovarian cancer risk . Glycaemic index ( GI ) and glycaemic load ( GL ) are measures that allow the carbohydrate content of individual foods to be classified according to their postpr and ial glycaemic effects and hence their effects on circulating insulin levels . Therefore , we examined ovarian cancer risk in association with GI and GL , and intake of dietary carbohydrate and sugar . METHODS The study was conducted in a prospect i ve cohort of 49 613 Canadian women enrolled in the National Breast Screening Study ( NBSS ) who completed a self-administered food-frequency question naire ( FFQ ) between 1980 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . Data from the FFQ were used to estimate overall GI and GL , and Cox proportional hazards models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the association between energy-adjusted quartile levels of GL , overall GI , total carbohydrates , total sugar and ovarian cancer risk . RESULTS During a mean 16.4 years of follow-up , we observed 264 incident ovarian cancer cases . GI and total carbohydrate and sugar intakes were not associated with ovarian cancer risk in the total cohort . GL was positively associated with a 72 % increase in risk of ovarian cancer ( HR=1.72 , 95 % CI=1.13 - 2.62 , Ptrend=0.01 ) and the magnitude of the association was slightly greater among postmenopausal ( HR=1.89 , 95 % CI=0.98 - 3.65 , Ptrend=0.03 ) than among premenopausal women ( HR=1.64 , 95 % CI=0.95 - 2.88 , Ptrend=0.07 ) . CONCLUSIONS Our data suggest that consumption of diets with high GL values may be associated with increased risk of ovarian cancer The associations of dietary total carbohydrates , overall glycemic index , total dietary glycemic load , total sugars , total starch , and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospect i ve Investigation into Cancer and Nutrition cohort ( 1992 - 2004 ) , including 710 incident cases diagnosed during a mean 6.4 years of follow-up . Cox proportional hazards models were used to estimate relative risks and 95 % confidence intervals . There were no statistically significant associations with endometrial cancer risk for increasing quartile intakes of any of the exposure variables . However , in continuous models calibrated by using 24-hour recall values , the multivariable relative risks were 1.61 ( 95 % confidence interval : 1.06 , 2.45 ) per 100 g/day of total carbohydrates , 1.40 ( 95 % confidence interval : 0.99 , 1.99 ) per 50 units/day of total dietary glycemic load , and 1.36 ( 95 % confidence interval : 1.05 , 1.76 ) per 50 g/day of total sugars . These associations were stronger among women who had never used postmenopausal hormone therapy compared with ever users ( total carbohydrates p(heterogeneity ) = 0.04 ) . Data suggest no association of overall glycemic index , total starch , and total fiber with risk , and a possible modest positive association of total carbohydrates , total dietary glycemic load , and total sugars with risk , particularly among never users of hormone replacement therapy Analysis of prospect i ve follow-up data usually includes a Cox regression model . When a hazard rate ratio , obtained as the exponential of an estimated regression coefficient from the Cox model , is greater than 1.0 , it consistently exceeds relative risk , and is exceeded by the odds ratio . The divergence of these distinct epidemiologic measures increases with the product of three factors : ( 1 ) the length of follow-up , ( 2 ) the average rate of the end point occurence over the follow-up period , and ( 3 ) the magnitude of risk , either above or below 1 . Cornfield 's rare disease assumption is basically the product of the first two of these factors . However , risks in excess of 2.5 have a powerful effect on the divergence of these measures , and this point has received less emphasis . Conversely , and as seen frequently in applications , relative risk , hazard rate ratio , and odds ratio numerically approximate one another with shorter follow-up , rarer end points , and risks closer to 1 . Although the hazard rate ratio is not always distinguished from relative risk , it is commonly close to , and is always between , relative risk and the odds ratio . Consistent and accurate terminology would have us use hazard rate ratio with Cox regression and odds ratio with logistic regression . The term " relative risk " seems to be a default choice , regardless of the model being used . However , when relative risk is the object of the model chosen , as in a Poisson regression approximation of two binomial proportions or an equivalent weighted least squares , then for us , relative risk is the accurate terminology OBJECTIVE High-glycaemic-load diets may increase endometrial cancer risk by increasing circulating insulin levels and , as a consequence , circulating oestrogen levels . Given the paucity of epidemiological data regarding the relationship between dietary glycaemic index and glycaemic load and endometrial cancer risk , we sought to examine these associations using data from a prospect i ve cohort study . DESIGN , SETTING AND SUBJECTS We examined the association between dietary glycaemic load and endometrial cancer risk in a cohort of 49,613 Canadian women aged between 40 and 59 years at baseline who completed self-administered food-frequency question naires between 1982 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . RESULTS During a mean of 16.4 years of follow-up , we observed 426 incident cases of endometrial cancer . Hazard ratios for the highest versus the lowest quartile level of overall glycaemic index and glycaemic load were 1.47 ( 95 % confidence interval ( CI ) = 0.90 - 2.41 ; P for trend = 0.14 ) and 1.36 ( 95 % CI = 1.01 - 1.84 ; P for trend = 0.21 ) , respectively . No association was observed between total carbohydrate or total sugar consumption and endometrial cancer risk . Among obese women ( body mass index > 30 kg m(-2 ) ) the hazard ratio for the highest versus the lowest quartile level of glycaemic load was 1.88 ( 95 % CI = 1.08 - 3.29 ; P for trend = 0.54 ) and there was a 55 % increased risk for the highest versus the lowest quartile level of glycaemic load among premenopausal women . There was also evidence to support a positive association between glycaemic load and endometrial cancer risk among postmenopausal women who had used hormone replacement therapy . CONCLUSIONS Our data suggest that diets with high glycaemic index or high glycaemic load may be associated with endometrial cancer risk overall , and particularly among obese women , premenopausal women and postmenopausal women who use hormone replacement therapy OBJECTIVE To examine prospect ively the relationship between glycemic diets , low fiber intake , and risk of non-insulin-dependent diabetes mellitus . DESIGN Cohort study . SETTING In 1986 , a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease , cancer , and diabetes completed a detailed dietary question naire from which we calculated usual intake of total and specific sources of dietary fiber , dietary glycemic index , and glycemic load . MAIN OUTCOME MEASURE Non-insulin-dependent diabetes mellitus . RESULTS During 6 years of follow-up , 915 incident cases of diabetes were documented . The dietary glycemic index was positively associated with risk of diabetes after adjustment for age , body mass index , smoking , physical activity , family history of diabetes , alcohol and cereal fiber intake , and total energy intake . Comparing the highest with the lowest quintile , the relative risk ( RR ) of diabetes was 1.37 ( 95 % confidence interval [ CI ] , 1.09 - 1.71 , P trend=.005 ) . The glycemic load ( an indicator of a global dietary insulin dem and ) was also positively associated with diabetes ( RR= 1.47 ; 95 % CI , 1.16 - 1.86 , P trend=.003 ) . Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles ( RR=0.72 , 95 % CI , 0.58 - 0.90 , P trend=.001 ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes ( RR=2.50 , 95 % CI , 1.14 - 5.51 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes Conditions related to chronic hyperinsulinemia , such as obesity , noninsulin dependent diabetes mellitus and polycystic ovary syndrome , are associated with an increased risk of endometrial cancer . Elevated plasma IGF‐I and decreased levels of IGF‐binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies . We investigated for the first time in a prospect i ve study the association of pre‐diagnostic blood concentrations of C‐peptide ( a marker of pancreatic insulin production ) , IGF‐I , IGFBP‐1 , ‐2 and ‐3 with endometrial cancer risk . A case‐control study was nested within 3 cohorts in New York ( USA ) , Umeå ( Sweden ) and Milan ( Italy ) . It included 166 women with primary invasive endometrial cancer and 315 matched controls , of which 44 case and 78 control subjects were premenopausal at recruitment . Endometrial cancer risk increased with increasing levels of C‐peptide ( ptrend = 0.0002 ) , up to an odds ratio ( OR ) of 4.76 [ 95 % confidence interval ( CI ) = 1.91–11.8 ] for the highest quintile . This association remained after adjustment for BMI and other confounders [ OR for the top quintile = 4.40 ( 1.65–11.7 ) ] . IGFBP‐1 levels were inversely related to endometrial cancer [ ptrend = 0.002 ; OR in the upper quintile = 0.30 ( 0.15–0.62 ) ] , but the association was weakened and lost statistical significance after adjustment for confounders [ ptrend = 0.06 ; OR in the upper quintile = 0.49 ( 0.22–1.07 ) ] . Risk was unrelated to levels of IGF‐I , IGFBP‐2 and IGFBP‐3 . Chronic hyperinsulinemia , as reflected by increased circulating C‐peptide , is associated with increased endometrial cancer risk . Decrease in the prevalence of chronic hyperinsulinemia , through changes in lifestyle or medication , is expected to prevent endometrial cancer . © 2003 Wiley‐Liss , Objective To examine the association between anthropometry and endometrial cancer , particularly by menopausal status and exogenous hormone use subgroups . Methods Among 223,008 women in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study , there were 567 incident endometrial cancer cases during 6.4 years of follow-up . The analysis was performed with Cox proportional hazards modeling . Results Weight , body mass index ( BMI ) , waist and hip circumferences and waist – hip ratio ( WHR ) were strongly associated with increased risk of endometrial cancer . The relative risk ( RR ) for obese ( BMI 30– < 40 kg/m2 ) compared to normal weight ( BMI < 25 ) women was 1.78 , 95 % CI = 1.41–2.26 , and for morbidly obese women ( BMI ≥ 40 ) was 3.02 , 95 % CI = 1.66–5.52 . The RR for women with a waist circumference of ≥88 cm vs. < 80 cm was 1.76 , 95 % CI = 1.42–2.19 . Adult weight gain of ≥20 kg compared with stable weight ( ±3 kg ) increased risk independent of body weight at age 20 ( RR = 1.75 , 95 % CI = 1.11–2.77 ) . These associations were generally stronger for postmenopausal than premenopausal women , and oral contraceptives never-users than ever-users , and much stronger among never-users of hormone replacement therapy compared to ever-users . Conclusion Obesity , abdominal adiposity , and adult weight gain were strongly associated with endometrial cancer risk . These associations were particularly evident among never-users of hormone replacement therapy We set out to study the relationship between circulating levels of IGF-I and its major binding protein ( IGFBP-3 ) in relation to ovarian cancer risk . We conducted a case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition . Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum sample s of 214 women who subsequently developed ovarian cancer , and 388 matched control subjects . Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels . For all women , there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer . However , among women diagnosed with ovarian cancer aged 55 or younger , the relative risk was higher in the middle or top tertiles of serum IGF-I , when compared with women in the lowest tertile ( odds ratios ( OR ) = 1.8 ( 95%CI 0.7 - 4.3 ) and OR = 2.4 ( 95%CI 0.9 - 6.4 ) ; P(trend ) = 0.08 ) respectively . These results were adjusted for body mass index , previous hormone use , fertility problems , and parity . Restricting the analysis to women who were premenopausal at blood donation , relative risks for ovarian cancer diagnosed before age 55 were higher ( OR = 5.1 ( 95%CI 1.5 - 18.2 ) and OR = 5.6 ( 95%CI 1.5 - 20.8 ) respectively , for second and third tertiles ; P(trend ) = 0.02 ) . Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates . Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I , but less strong and statistically not significant . In women aged over 55 , there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk . Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age |
2,303 | 27,635,951 | CONCLUSION Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow | BACKGROUND Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown .
OBJECTIVE We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery . | Background . The local anaesthetics used in day-case spinal anaesthesia should provide short recovery times . We aim ed to compare hyperbaric prilocaine and bupivacaine in terms of sensory block resolution and time to home readiness in day-case spinal anaesthesia . Methods . Fifty patients undergoing perianal surgery were r and omized into two groups . The bupivacaine-fentanyl group ( Group B ) received 7.5 mg , 0.5 % hyperbaric bupivacaine + 20 μg fentanyl in total 1.9 mL. The prilocaine-fentanyl group ( Group P ) received 30 mg , 0.5 % hyperbaric prilocaine + 20 μg fentanyl in the same volume . Results . Time to L1 block and maximum block was shorter in Group P than in Group B ( Group P 4.6 ± 1.3 min versus Group B 5.9 ± 01.9 min , P = 0.017 , and Group P 13.2 ± 7.5 min versus Group B 15.3 ± 6.6 min , P = 0.04 ) . The time to L1 regression and S3 regression of the sensorial block was significantly shorter in Group P than in Group B ( 45.7 ± 21.9 min versus 59.7 ± 20.9 min , P = 0.024 , and 133.8 ± 41.4 min versus 200.4 ± 64.8 min , P < 0.001 ) . The mean time to home readiness was shorter for Group P than for Group B ( 155 ± 100.2 min versus 207.2 ± 62.7 min ( P < 0.001 ) ) . Conclusion . Day-case spinal anaesthesia with hyperbaric prilocaine + fentanyl is superior to hyperbaric bupivacaine in terms of earlier sensory block resolution and home readiness and the surgical conditions are comparable for perianal surgery BACKGROUND : In this prospect i ve , r and omized , double-blind study , we evaluated whether a very low dose of spinal bupivacaine could be sufficient for safe performance of short perianal surgery . METHODS : Eighty patients were r and omly assigned to receive hyperbaric bupivacaine doses of either 1.5 mg ( n = 40 ) or 6.0 mg ( n = 40 ) . RESULTS : The lower dose produced satisfactory anesthesia with a more limited block ( median S4 ; P < 0.01 ) , earlier time to ambulation ( 98 vs 147 min ; P < 0.01 ) , and hospital discharge ( 126 vs 249 min ; P < 0.01 ) , compared with the higher spinal dose . CONCLUSIONS : The use of 1.5 mg spinal bupivacaine can be successful for short perianal surgery Background : Spinal anesthesia for knee arthroscopy can be produced with a low dose of bupivacaine , but additional intrathecal drugs are often required to lower the risk of failed blocks . We investigated the effect of the addition of clonidine ( 0 , 15 or 30 μg ) to 5 mg hyperbaric bupivacaine on the duration of the motor block , analgesic quality and ability to void after the surgery in a r and omized controlled trial Background Given the current practice environment , it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs . The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting . Methods Ninety-three consenting adult out patients undergoing anorectal surgery were r and omly assigned to one of three anesthetic treatment groups : group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine , 2 % , and 15 ml bupivacaine , 0.5 % , with epinephrine ( 1:200,000 ) in combination with intravenous sedation using a propofol infusion , 25–100 & mgr;g · kg−1 · min−1 ; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 & mgr;g fentanyl with midazolam , 1–2-mg intravenous bolus doses ; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5–2 % sevoflurane in combination with 65 % nitrous oxide . In groups 2 and 3 , the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision . Results The mean costs were significantly decreased in group 1 ( $ 69 ± 20 compared with $ 104 ± 18 and $ 145 ± 25 in groups 2 and 3 , respectively ) because both intraoperative and recovery costs were lowest ( P < 0.05 ) . Although the surgical time did not differ among the three groups , the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 ( vs. groups 2 and 3 ) . There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations . However , the need for pain medication was less in groups 1 and 2 ( 19 % and 19%vs . 45 % for group 3;P < 0.05 ) . Patients in group 1 had no complaints of nausea ( vs. 3 % and 26 % in groups 2 and 3 , respectively ) . More patients in group 1 ( 68 % ) were highly satisfied with the care they received than in groups 2 ( 58 % ) and 3 ( 39 % ) . Conclusions The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting BACKGROUND The effects of volume and baricity of spinal bupivacaine on block onset , height , duration , and hemodynamics were studied . METHODS Ninety patients undergoing endoscopic urologic procedures were r and omized to receive 10 mg of intrathecal bupivacaine at L2-L3 level in sitting position . In the operating room , commercial products were diluted as needed with NaCl 0.9 % to obtain isobaric solutions ( density , 1.005 - 1.008 ) or with NaC 10.9 % and glucose 30 % to obtain hyperbaric solutions ( density , 1.031 - 1.037 ) of 2 , 5 , or 10 ml ( six groups of 15 patients each ) . Three minutes after spinal injection the patients were placed in lithotomy position . Sensory blockade was assessed using pinprick and cold sensation tests , and motor blockade was assessed using a four-point scale . RESULTS Onset times to maximal cephalad spread of spinal blockade were similar with isobaric and hyperbaric solutions . A greater maximal cephalad spread of anesthesia was obtained with diluted isobaric bupivacaine but was not associated with more hypotension . Volume had no effect on cephalad extent of anesthesia with hyperbaric bupivacaine . Times for regression of anesthesia to L2 and offset of motor block were longer with isobaric than with hyperbaric solutions of bupivacaine . The intensity of motor blockade was decreased with diluted hyperbaric bupivacaine . No patient reported back pain . CONCLUSION In this study , volume had no significant influence on either cephalad spread or duration of sensory blockade for either isobaric or hyperbaric bupivacaine . Time for offset of anesthesia was shorter with hyperbaric bupivacaine compared with isobaric solutions This study investigated whether the addition of 25 μg fentanyl to an ultra-low ( sub-anaesthetic ) dose of intrathecal bupivacaine provides adequate anaesthesia for out-patient anorectal surgery , without increasing side-effects or delaying hospital discharge . Patients were r and omly allocated to receive 2.5 mg 0.5 % bupivacaine plus 25 μg fentanyl ( group BF , n = 18 ) or 5 mg 0.5 % bupivacaine alone ( group B , n = 17 ) . There were no significant differences in intra-operative outcomes , but mean recovery and discharge times were significantly shorter in group BF . There were no between-group differences in hypotension , bradycardia or respiratory depression and post-operative complications were comparable , apart from pruritus which was significantly more frequent in group BF . Fewer patients requested analgesic medication in the early post-operative period in group BF than in group B. In conclusion , 25 μg intrathecal fentanyl added to ultra-low dose ( 2.5 mg ) bupivacaine provided good- quality spinal anaesthesia and reduced post-operative analgesic requirement in patients undergoing ambulatory anorectal surgery The effect of adding epinephrine to small doses of spinal bupivacaine on the duration of sensory motor block has not been carefully investigated . Twelve volunteers underwent hyperbaric bupivacaine spinal anesthesia ( 7.5 mg ) with and without epinephrine ( 0.2 mg ) in a r and omized , double-blind , cross-over fashion . Sensory block was assessed with pinprick , transcutaneous electrical stimulation ( TES ) equivalent to surgical stimulation ( at umbilicus , pubis , knee , and ankle ) , and tolerance of a pneumatic thigh tourniquet . Motor block was assessed with isometric force dynamometry . Discharge criteria were defined as return of pinprick sensation to dermatome S2 , ability to ambulate , and ability to urinate . Extent of sensory block to pinprick over time was unaffected by the addition of epinephrine . However , epinephrine prolonged tolerance of TES at the pubis , knee , and ankle ( 33 - 48 min , P < 0.05 ) and of thigh tourniquet ( 30 min , P < 0.01 ) . Motor block was prolonged by epinephrine at the quadriceps and gastrocnemius muscles ( by 23 and 51 min , respectively , P < 0.002 ) . Achievement of discharge criteria was prolonged by 48 min by the addition of epinephrine ( P < 0.01 ) . Thus , epinephrine may prolong surgical anesthesia for lower abdominal and lower extremity surgery and delay time until patients achieve discharge criteria . Implication s : Using a cross-over study design , 12 volunteers underwent bupivacaine spinal anesthesia with and without epinephrine . This study suggests that adding epinephrine to bupivacaine may prolong surgical anesthesia and also delay patients ' discharge . ( Anesth Analg 1998;86:973 - 7 In 60 patients undergoing inguinal hernia repair , we compared the clinical profile of unilateral spinal anesthesia produced with either 8 mg of hyperbaric bupivacaine 0.5 % ( n = 20 ) , 8 mg of hyperbaric levobupivacaine 0.5 % ( n = 20 ) , or 12 mg of hyperbaric ropivacaine 0.5 % ( n = 20 ) . The study drug was injected slowly through a 25-gauge Whitacre directional needle and patients maintained the lateral decubitus position for 15 min . The onset time and intraoperative efficacy were similar in the three groups . The maximal level of sensory block on the operative and nonoperative sides was T6 ( T12–5 ) and L3 ( /[no sensory level detectable]–T4 ) with bupivacaine , T8 ( T12–5 ) and L3 ( /–T3 ) with levobupivacaine , T5 ( T10–2 ) and T11 ( /–T3 ) with ropivacaine ( P = 0.11 , P = 0.23 , respectively ) . Complete regression of spinal anesthesia occurred after 166 ± 42 min with ropivacaine , 210 ± 63 min with levobupivacaine , and 190 ± 51 min with bupivacaine ( P = 0.03 and P = 0.04 , respectively ) ; however , no differences were observed in time for home discharge ( 329 ± 89 min with bupivacaine , 261 ± 112 min with levobupivacaine , and 332 ± 57 min with ropivacaine [ P = 0.28 ] ) . We conclude that 8 mg of levobupivacaine or 12 mg of ropivacaine are acceptable alternatives to 8 mg of bupivacaine when limiting spinal block at the operative side for inguinal hernia repair Background : Combination of local anesthetic and opioid enables the use of less spinal anesthetic and increases the success of anesthesia . Intrathecal opioid does not prolong motor recovery and thus should not delay discharge home . We hypothesized that 3 mg of hyperbaric bupivacaine with 10 µg of fentanyl permits fast‐tracking or shorter stay in post anesthesia care unit ( PACU ) , and earlier discharge home , compared with 4 mg of hyperbaric bupivacaine Background : We undertook this study to ascertain if a small dose of clonidine ( 30 μg ) when added to a bupivacaine-fentanyl mixture improves spinal analgesia , without producing side effects , as compared to a bupivacaine-fentanyl or a bupivacaine-clonidine mixture . Material s and Methods : In this prospect i ve , r and omized , double-blind study , 75 ( American Society of Anesthesiologists ) ASA grade I-II patients , aged between 45 and 65 years , who were scheduled for vaginal hysterectomy with pelvic floor repair or non-descent vaginal hysterectomy under spinal anesthesia were recruited . The patients received hyperbaric bupivacaine ( 2.3 ml ) with fentanyl 15 μg ( Group BF ) or clonidine 30 μg ( Group BC ) or both fentanyl ( 15 μg ) and clonidine ( 30 μg ) ( Group BCF ) . The total amount of intrathecal mixture was constant ( 2.8 ml ) in all the groups . Duration of sensory , motor block and effective analgesia , hemodynamic profile , postoperative pain score and analgesic requirements were recorded . Results : The duration of effective analgesia , mean time till two-segment regression , and duration of sensory and motor block were significantly longer in group BCF as compared to group BC ( P ~ 0.002 ) , and in group BC as compared to group BF ( P ~ 0.01 ) . The incidence of intraoperative pain and requirement of postoperative analgesics in the first 24 hours was significantly more in group BF as compared to the other groups ( P ~ 0.01 ) . There was no difference in the hemodynamic profile between the groups . Conclusion : Low-dose clonidine ( 30 μg ) when added to a bupivacaine-fentanyl mixture increased the duration of effective analgesia and the duration of sensory and motor block in gynecological surgery . The incidence of intraoperative pain and requirement of postoperative analgesics was significantly less when clonidine was added to intrathecal bupivacaine with or without fentanyl BACKGROUND The aim of this study was to compare the clinical effects of ' hyperbaric ' bupivacaine for spinal anaesthesia with those of similar preparations of levobupivacaine and ropivacaine . METHODS Sixty ASA grade I-II patients undergoing elective surgery under spinal anaesthesia were r and omized to receive 3 ml of bupivacaine , levobupivacaine , or ropivacaine , each at 5 mg ml(-1 ) and made hyperbaric by the addition of glucose 30 mg ml(-1 ) . A st and ard protocol was followed after which a blinded observer assessed the sensory and motor blocks . The level and duration of sensory ( pinprick ) block , intensity and duration of motor block , and time to mobilize and to micturate were also recorded . RESULTS One patient ( ropivacaine group ) required general anaesthesia because of technical failure , but all the other blocks were adequate . There were no significant differences between the groups with regard to the mean time to onset of sensory block at T10 , the extent of spread , or mean time to maximum spread . Regression of sensory block in the ropivacaine group was more rapid as demonstrated by duration at T10 ( P<0.0167 ) and total duration of sensory block ( P<0.0167 ) . Patients in the ropivacaine group had more rapid recovery from motor block ( P<0.0167 ) and shorter times to independent mobilization ( P<0.0167 ) . There were no significant differences between the bupivacaine and the levobupivacaine groups . CONCLUSIONS ' Hyperbaric ' ropivacaine provides reliable spinal anaesthesia of shorter duration than bupivacaine or levobupivacaine , both of which are clinical ly indistinguishable . The recovery profile of ropivacaine may be useful where prompt mobilization is required BACKGROUND A local anaesthetic with fast onset and short reliable duration of anaesthesia may be preferable for out-patient lower limb surgery . Articaine is believed to act faster and to have a shorter duration of action than bupivacaine , but there are no conclusive data available . The purpose of this study was to compare articaine and bupivacaine for day-case lower limb surgery . METHODS Eighty patients planned for day-case lower limb surgery enrolled in this study . Patients were r and omized to receive hyperbaric articaine 80 mg or plain bupivacaine 15 mg intrathecally . Primary outcome variable was recovery time from motor block . Secondary outcomes were : onset of sensory and motor block , maximum spread of sensory block , time to micturition , discharge from the hospital , and complications . RESULTS The groups were comparable for the medians and the range of the maximum blocks after 30 min . Median time to complete regression of motor block was 101 min ( range 80 - 129 ) for articaine compared with 307 min ( range 225 - 350 ) for bupivacaine ( P<0.0005 ) . First spontaneous micturition occurred after 257 min ( 210 - 293 ) in the articaine group and after 350 min ( 304 - 370 ) in the bupivacaine group ( P<0.0005 ) . In the articaine and bupivacaine groups , patients were discharged after 300 min ( 273 - 347 ) and 380 min ( 332 - 431 ) , respectively ( P<0.0005 ) . There was no significant difference in the occurrence of complications between the groups . CONCLUSIONS Spinal anaesthesia with 80 mg of hyperbaric articaine has a shorter duration than a spinal anaesthesia with 15 mg of plain bupivacaine in lower limb surgery of approximately 1 h duration Summary We evaluated the effect of low‐dose bupivacaine plus fentanyl administered intrathecally in elderly patients undergoing transurethral prostatectomy . Patients were r and omly assigned to one of two groups . Group F received plain bupivacaine 4 mg with 25 µg of fentanyl and sterile water to a total of 1.5 ml , and Group B received only 0.5 % plain bupivacaine 7.5 mg for spinal anaesthesia . Sensory block was adequate for surgery in all patients . The mean level of motor block was higher and the duration of motor block was longer in Group B ( p < 0.0001 ) . Hypotension and shivering were significantly more common in Group B ( p < 0.05 ) . The addition of fentanyl 25 µg to plain bupivacaine 4 mg provides adequate analgesia for transurethral prostatectomy with fewer side‐effects in elderly patients when compared with the conventional dose of bupivacaine The aim of this r and omised , double-blind study was to compare equipotent doses of plain ropivacaine and bupivacaine ( 19.5 mg and 13 mg respectively ) , both with fentanyl 20 μg , for spinal anaesthesia in lower abdominal surgery . After written informed consent had been obtained , 52 ASA I to II male patients scheduled for lower abdominal surgery were r and omly assigned to receive intrathecal plain ropivacaine 19.5 mg with fentanyl 20 μg ( group R , n=26 ) or plain bupivacaine 13 mg with fentanyl 20 μg ( group B , n=26 ) in 3 ml . The level and duration of sensory block , intensity and duration of motor block , time to mobilise and patient satisfaction were recorded . All patients achieved sensory block to T10 or higher . The level of sensory block was significantly higher in group B ( T4 [ T3 to T7 ] vs T7 [ T4 to T9 ] , P < 0.05 ) . There was no difference in the onset time of motor block . The duration of motor block ( Bromage score > 0 ) was shorter in group R ( 139±39 minutes vs group B 182±46 minutes , P < 0.05 ) . The duration and intensity of complete motor block ( Bromage score=3 ) were also shorter in group R ( 90±25 minutes vs 130±40 minutes , P < 0.05 ) . We conclude that plain ropivacaine 19.5 mg plus fentanyl 20 μg is associated with a lower level of sensory block and a shorter duration of motor block when compared to bupivacaine 13 mg plus fentanyl 20 μg for spinal anaesthesia in lower abdominal surgery Background : Inguinal herniorrhaphy is commonly performed as an outpatient procedure . Spinal anesthesia offers some advantages over general anesthesia in this setting The aim of this r and omized double-blinded study was to see whether the addition of small-dose clonidine to small-dose bupivacaine for spinal anesthesia prolonged the duration of postoperative analgesia and also provided a sufficient block duration that would be adequate for inguinal herniorrhaphy . We r and omized 45 patients to 3 groups receiving intrathecal hyperbaric bupivacaine 6 mg combined with saline ( Group B ) , clonidine 15 & mgr;g ( Group BC15 ) , or clonidine 30 & mgr;g ( Group BC30 ) ; all solutions were diluted with saline to 3 mL. The sensory block level was insufficient for surgery in five patients in Group B , and these patients were given general anesthesia . Patients in Groups BC15 and BC30 had a significantly higher spread of analgesia ( two to four dermatomes ) than those in Group B. Two-segment regression , return of S1 sensation , and regression of motor block were significantly longer in Group BC30 than in Group B. The addition of clonidine 15 and 30 & mgr;g to bupivacaine prolonged time to first analgesic request and decreased postoperative pain with minimal risk of hypotension . We conclude that clonidine 15 & mgr;g with bupivacaine 6 mg produced an effective spinal anesthesia and recommend this dose for inguinal herniorrhaphy , because it did not prolong the motor block Ambulatory surgery continues to increase nationwide . Because spinal lidocaine is associated with transient neurologic symptoms , many clinicians have switched to small-dose bupivacaine for outpatient spinal anesthesia . However , bupivacaine often produces inadequate surgical anesthesia and has an unpredictable duration . Preservative-free 2-chloroprocaine ( 2-CP ) has reemerged as an alternative for outpatient spinal anesthesia . We design ed this double-blind , r and omized , crossover , volunteer study to compare 40 mg of 2-CP with small-dose ( 7.5 mg ) bupivacaine with measures of pinprick anesthesia , motor strength , tolerance to tourniquet and electrical stimulation , and simulated discharge criteria . Peak block height ( 2-CP average T7 [ range T3–10 ] ; bupivacaine average T9 [ range T4–L1 ] ) , regression to L1 ( 2-CP 64 ± 10 versus bupivacaine 87 ± 41 min ) , and tourniquet tolerance ( 2-CP 52 ± 11 versus bupivacaine 60 ± 27 min ) did not differ between drugs ( P = 0.15 , 0.12 , and 0.40 , respectively ) . However , time to simulated discharge ( including time to complete block regression , ambulation , and spontaneous voiding ) was significantly longer with bupivacaine ( 2-CP 113 ± 14 , bupivacaine 191 ± 30 min , P = 0.0009 ) . No subjects reported transient neurologic symptoms or other side effects . We conclude that spinal 2-CP provides adequate duration and density of block for ambulatory surgical procedures , and has significantly faster resolution of block and return to ambulation compared with 7.5 mg of bupivacaine STUDY OBJECTIVE To compare the effects of intrathecal ropivacaine with bupivacaine in a dose ratio of 2:1 for outpatient arthroscopic knee surgery . DESIGN R and omized , single-blinded study . SETTING University-affiliated hospital . PATIENTS 90 patients scheduled for outpatient arthroscopic knee surgery . INTERVENTIONS Patients were r and omized and assigned in single-blinded fashion to receive a 3-mL solution of either 15 mg of isobaric ropivacaine ( group R ; n = 45 ) or 7.5 mg of isobaric bupivacaine ( group B ; n = 45 ) through a 27-gauge Quincke spinal needle at the L(3 ) to L(4 ) interspace , while placed in the lateral decubitus position . MEASUREMENTS Onset and offset times for sensory and motor block ; highest level of sensory block ; duration of the sensory and motor block ; first ambulation , urination , and discharge time ; mean arterial pressure ; and heart rate were all recorded . MAIN RESULTS Onset time for sensory block ( mean + /- SD ) to L1 and time until sensory block regressed to L2 were shorter in group R. Complete motor block occurred in 40 patients with ropivacaine and 45 patients with bupivacaine . First ambulation and first urination and discharge times were similar between the two groups . Cephalad spread of sensory block was higher with ropivacaine ( P < 0.05 ) . The median ( range ) upper sensory level obtained with bupivacaine was T11 ( T6-L1 ) and T8 ( T6-T10 ) with ropivacaine . Hemodynamic changes were similar between the groups ( P > 0.05 ) . CONCLUSION Isobaric ropivacaine 15 mg provided a higher sensory block level and shorter sensorial onset and offset times than did 7.5 mg of isobaric bupivacaine BACKGROUND This study was design ed to test a treatment algorithm for management of bladder function after outpatient general or local anesthesia . METHODS Three hundred twenty-four out patients , stratified into risk categories for urinary retention , were studied . Patients in category 1 were low-risk patients ( n = 227 ) having non-pelvic surgery and r and omly assigned to receive 10 ml/kg or 2 ml/kg of intravenous fluid intraoperatively . They were discharged when otherwise ready , without being required to void . Patients in category 2 ( n = 40 ) , also presumed to be low risk , had gynecologic surgery . High-risk patients included 31 patients having hernia or anal surgery ( category 3 ) , and 31 patients with a history of retention ( category 4 ) . Bladder volumes were monitored by ultrasound in those in categories 2 - 4 , and patients were required to void ( or be catheterized ) before discharge . The incidence of retention and urinary tract symptoms after surgery were determined for all categories . RESULT Urinary retention affected 0.5 % of category 1 patients and none of category 2 patients . Median time to void after discharge was 75 min ( interquartile range 120 ) in category 1 patients ( n = 27 ) discharged without voiding . Fluids administered did not alter incidence of retention or time to void . Retention occurred in 5 % of high-risk patients before discharge and recurred in 25 % after discharge . CONCLUSION In reliable patients at low risk for retention , voiding before discharge appears unnecessary . In high-risk patients , continued observation until the bladder is emptied is indicated to avoid prolonged overdistention of the bladder This prospect i ve , observer‐blinded , r and omised , multicentre study aim ed at determining the non‐inferiority of 50 mg of plain 1 % 2‐chloroprocaine vs. 10 mg of 0.5 % plain bupivacaine in terms of sensory block onset time at T10 after spinal injection . The study hypothesis was that the difference in onset times of sensory block to T10 between the two drugs is ≤ 4 min The use of an ilioinguinal-hypogastric nerve block ( IHNB ) as part of a monitored anesthesia care ( MAC ) technique has been associated with a rapid recovery profile for out patients undergoing inguinal herniorrhaphy procedures . This study was design ed to compare the cost-effectiveness of an IHNB-MAC technique with st and ardized general and spinal anesthetics techniques for inguinal herniorrhaphy in the ambulatory setting . We r and omly assigned 81 consenting out patients to receive IHNB-MAC , general anesthesia , or spinal anesthesia . We evaluated recovery times , 24-h postoperative side effects and associated incremental costs . Compared with general and spinal anesthesia , patients receiving IHNB-MAC had the shortest time-to-home readiness ( 133 ± 68 min vs 171 ± 40 and 280 ± 83 min ) , lowest pain score at discharge ( 15 ± 14 mm vs 39 ± 28 and 34 ± 32 mm ) , and highest satisfaction at 24-h follow-up ( 75 % vs 36 % and 64 % ) . The total anesthetic costs were also the least in the IHNB-MAC group ( $ 132.73 ± 33.80 vs $ 172.67 ± 29.82 and $ 164.97 ± 31.03 ) . We concluded that IHNB-MAC is the most cost-effective anesthetic technique for out patients undergoing unilateral inguinal herniorrhaphy with respect to speed of recovery , patient comfort , and associated incremental costs . Implication s Local anesthesia with propofol sedation for inguinal hernia repair was associated with a faster recovery , higher patient satisfaction , and lower costs compared with general and spinal anesthesia Background We have always been search ing for the ideal local anesthetic for outpatient spinal anesthesia . Lidocaine has been associated with a high incidence of transient neurological symptoms , and bupivacaine produces sensory and motor blocks of long duration . Preservative-free 2-chloroprocaine ( 2-CP ) seems to be a promising alternative , being a short-acting agent of increasing popularity in recent years . This study was design ed to compare 2-CP with bupivacaine for spinal anesthesia in an elective ambulatory setting . Methods A total of 106 patients were enrolled in this r and omized double-blind study . Spinal anesthesia was achieved with 0.75 % hyperbaric bupivacaine 7.5 mg ( n = 53 ) or 2 % preservative-free 2-CP 40 mg ( n = 53 ) . The primary endpoint for the study was the time until reaching eligibility for discharge . Secondary outcomes included the duration of the sensory and motor blocks , the length of stay in the postanesthesia care unit , the time until ambulation , and the time until micturition . Results The average time to discharge readiness was 277 min in the 2-CP group and 353 min in the bupivacaine group , a difference of 76 min ( 95 % confidence interval [ CI ] : 40 to 112 min ; P < 0.001 ) . The average time for complete regression of the sensory block was 146 min in the 2-CP group and 329 min in the bupivacaine group , a difference of 185 min ( 95 % CI : 159 to 212 min ; P < 0.001 ) . Times to ambulation and micturition were also significantly lower in the 2-CP group . ConclusionS pinal 2-chloroprocaine provides adequate duration and depth of surgical anesthesia for short procedures with the advantages of faster block resolution and earlier hospital discharge compared with spinal bupivacaine . ( Clinical Trials.gov number , NCT00845962).Résumé Context eNous sommes depuis toujours à la recherche de l’anesthésique local idéal pour l’anesthésie rachidienne ambulatoire . La lidocaïne a été associée à une incidence élevée de symptômes neurologiques temporaires , et la bupivacaïne produit des blocs sensitifs et moteurs de longue durée . La 2-chloroprocaïne ( 2-CP ) sans agent de conservation semble être une alternative prometteuse , étant donné qu’il s’agit d’un agent à courte action qui gagne en popularité depuis quelques années . Cette étude a été conçue afin de comparer la 2-CP à la bupivacaïne pour la rachianesthésie dans un context e ambulatoire et non urgent . MéthodeAu total , 106 patients ont été recrutés dans cette étude r and omisée à double insu . La rachianesthésie a été réalisée avec 7,5 mg de bupivacaïne hyperbare 0,75 % ( n = 53 ) ou 40 mg de 2-CP sans agent de conservation à 2 % ( n = 53 ) . Le critère d’évaluation principal de l’étude était le délai jusqu’à l’éligibilité au congé . Les critères d’évaluation secondaires étaient la durée des blocs sensitifs et moteurs , la durée de séjour en salle de réveil , le temps jusqu’à ambulation et le temps jusqu’à miction . RésultatsLe délai moyen jusqu’à l’éligibilité au congé était de 277 min dans le groupe 2-CP et de 353 min dans le groupe bupivacaïne , soit une différence de 76 min ( intervalle de confiance [ IC ] 95 % : 40 à 112 min ; P < 0,001 ) . Le temps moyen jusqu’à régression du bloc sensitif était de 146 min dans le groupe 2-CP et de 329 min dans le groupe bupivacaïne , soit une différence de 185 min ( intervalle de confiance [ IC ] 95 % : 159 à 212 min ; P < 0,001 ) . Les temps jusqu’à ambulation et miction étaient également significativement plus bas dans le groupe 2-CP . Conclusion La 2-chloroprocaïne rachidienne procure une durée et une profondeur adéquates de l’anesthésie chirurgicale pour les interventions courtes et offre l’avantage d’une régression plus rapide du bloc et d’un congé plus rapide de l’hôpital par rapport à la bupivacaïne rachidienne . ( Numéro de Clinical Trials.gov , NCT00845962 ) The optimal anesthetic technique for outpatient knee arthroscopy remains controversial . In this study , we evaluated surgical operating conditions , patient satisfaction , recovery times , and postoperative analgesic requirements associated with psoas compartment block , general anesthetic , or spinal anesthetic techniques . Sixty patients were r and omized to receive a propofol/nitrous oxide/fentanyl general anesthetic , spinal anesthesia with 6 mg of bupivacaine and 15 & mgr;g of fentanyl , or psoas compartment block with 40 mL of 1.5 % mepivacaine . All patients received IV ketorolac and intraarticular bupivacaine . The frequency of postanesthesia recovery room admission was 13 ( 65 % ) of 20 for patients receiving general anesthesia , compared with 0 of 21 for patients receiving spinal anesthesia and 1 ( 5 % ) of 19 for patients receiving psoas block ( P < 0.001 ) . The median time from the end of surgery to meeting hospital discharge criteria did not differ across groups ( 131 , 129 , and 110 min for general , spinal , and psoas groups , respectively ) . In the hospital , 45 % of general anesthesia patients received opioid analgesics , compared with 14 % of spinal anesthesia and 21 % of psoas block patients ( P = 0.087 ) . There was no difference among groups with respect to the time of first analgesic use or the number of patients requiring opioid analgesia . Pain scores were highest in patients receiving general anesthesia at 30 min ( P = 0.032 ) and at 60 , 90 , and 120 min ( P < 0.001 ) . Patient satisfaction with anesthetic technique ( P = 0.025 ) and pain management ( P = 0.009 ) differed significantly across groups ; patients receiving general anesthesia reported lower satisfaction ratings . We conclude that spinal anesthesia or psoas block is superior to general anesthesia for knee arthroscopy when considering re source utilization , patient satisfaction , and postoperative analgesic management Ropivacaine , which blocks sensory nerve fibers more readily than motor fibers , is considered to be less potent than bupivacaine . Our hypothesis was that , when used in spinal anesthesia for day surgery , ropi-vacaine 15 and 20 mg would provide faster motor recovery than bupivacaine 10 mg . This prospect i ve , r and omized , double-blinded study included 90 ambulatory lower-extremity surgery patients who received 2 mL of ropivacaine 1 % , ropivacaine 0.75 % , or bupivacaine 0.5 % . Motor block was tested with the Bromage scale , and sensory block was tested with pinprick . Ropivacaine 15 mg provided faster recovery of motor block ( 150 min ) than did bupivacaine 10 mg ( 210 min ; P = 0.005 ) , but the median duration of sensory block at T10 ( 140 min ) did not differ significantly from that with bupivacaine 10 mg ( 140 min ) . The median duration of sensory block at T10 was significantly longer with ropivacaine 20 mg ( 170 min ) than with bupivacaine 10 mg ( 140 min ; P = 0.005 ) , but the median recovery from motor block ( 210 min ) did not differ significantly . We conclude that the duration of sensory block of ropivacaine was two thirds and the duration of motor block was half when compared with bupivacaine , with calculations based on the duration -per-milligram of the local anesthetic Background The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures . Methods Twenty men were r and omly allocated to receive either bupivacaine or lidocaine . Before spinal anesthesia , filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the st and ing position . After operation , cystometric measurements were continued until the patient could void urine spontaneously . The levels of analgesia and of motor blockade were recorded . Results The urge to void disappeared immediately after injection of the local anesthetics . There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine . Detrusor blockade lasted significantly longer in the bupivacaine group ( means + /‐ SD , 460 + /‐ 60 min ) than in the lidocaine group ( 235 + /‐ 30 min ) . Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group . In the bupivacaine group , the total volume of accumulated urine ( 875 + /‐385 ml ) was also significantly higher than cystometric bladder capacity ( 505 + /‐ 120 ml ) with the risk of over distension of the bladder . Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment . Conclusions Spinal anesthesia with lidocaine and with bupivacaine causes a clinical ly significant disturbance of bladder function due to interruption of the micturition reflex . The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients . With long‐acting local anesthetics , the volume of accumulated urine may exceed the cystometric bladder capacity . With respect to recovery of urinary bladder function , the use of short‐acting local anesthetics for spinal anesthesia seems to be preferable We conducted a double-blind comparison of three doses ( 7.5 mg , 8.75 mg and 10 mg ) of 0.5 % hyperbaric bupivacaine in women undergoing elective caesarean under spinal anaesthesia . Sixty women were r and omised into 3 groups of 20 . Group A received 7.5 mg , group B 8.75 mg and C 10 mg of study drug . The time to maximum sensory blockade did not differ among the groups ( P > 0.05 ) . Mean time to start of regression of sensory block was greater in group C than in groups A and B ( P < 0.001 and P < 0.05 respectively ) . Time required for complete regression of sensory block was longer in group C than in groups A and B ( P < 0.001 ) . Duration of motor block was greater in group C than in groups A and B ( P < 0.001 and < 0.05 respectively ) . Neonatal outcome was good in all the groups . None of the patients in any group experienced pain before delivery . After delivery of the baby , however , group C women had a lower incidence of visceral pain than did groups A and B ( P < 0.05 ) . The incidence of hypotension was greater in groups B and C than in group A ( P < 0.05 ) . Group C women had a greater incidence of bradycardia than did groups A and B ( P < 0.05 ) . The 7.5-mg dose of 0.5 % hyperbaric bupivacaine was observed to provide acceptable analgesia without any significant incidence of adverse effects such as maternal hypotension or bradycardia The safety of lidocaine spinal anesthesia has recently been called into question by reports of both permanent and transient neurologic toxicity . This study explored the possibility of adapting the longer acting spinal bupivacaine to ambulatory surgery . Sixty patients presenting for ambulatory arthroscopy were r and omized to four groups receiving the following spinal anesthetics : Group I ( 15 mg bupivacaine ) , 3 mL of 0.5 % spinal bupivacaine in 8 % dextrose ; Group II ( 10 mg bupivacaine ) , 2 mL of the 0.5 % spinal bupivacaine + 1 mL saline ; Group III ( 7.5 mg bupivacaine ) , 1.5 mL of the 0.5 % spinal bupivacaine + 1.5 mL saline ; Group IV ( 5 mg bupivacaine ) , 1 mL of the 0.5 % spinal bupivacaine + 2 mL saline . Maximum block height was T-5 in Group I versus T-8 in the other groups . Onset times to peak block were similar in all groups and averaged 14 min . Time to two-segment regression , complete regression , micturition , and discharge were significantly reduced from Group I to Group II and from Group II to Group III . Reductions in times between Groups III and IV did not achieve statistical significance . Times from placement of the spinal block until discharge were 471 + /- 35 , 260 + /- 15 , 202 + /- 14 , and 181 + /- 8 min , respectively , for the four groups . The intensity of motor block decreased significantly from group to group , such that 13 of the 15 patients in Group IV failed to achieve Bromage level 2 or 3 . The intensity of sensory block also decreased from group to group with four patients in Group IV having pain intraoperatively that required further treatment . Therefore , Group III provided the optimum combination of adequate depth of anesthesia and rapid recovery . The results of this study indicate that spinal anesthesia with 7.5 mg of 0.5 % bupivacaine in 8 % dextrose diluted with an equal volume of saline provides an acceptable spinal anesthetic for ambulatory arthroscopy with a recovery profile appropriate to the ambulatory setting . ( Anesth Analg 1996;83:716 - 20 BACKGROUND Prospect i ve data on the use of prilocaine for ambulatory spinal anaesthesia remain limited . We compared the behaviour and characteristics of subarachnoid block using prilocaine and fentanyl with that of bupivacaine and fentanyl . METHODS In a prospect i ve , double-blind , r and omized controlled trial , 50 patients undergoing elective ambulatory arthroscopic knee surgery received subarachnoid anaesthesia , with either prilocaine 20 mg and fentanyl 20 µg ( Group P ) or plain bupivacaine 7.5 mg and fentanyl 20 µg ( Group B ) . Primary endpoints included times for onset of maximum sensory block level and regression of sensory block to L4 , and also motor block at 1 and 2 h , and levels of haemodynamic stability . Comparisons between the groups were made by χ² test for proportions and the Mann-Whitney test for ordinal data . Time-to-event data were analysed by the Mann-Whitney test for uncensored data or the logrank test for censored data . RESULTS At 2 h , motor block in Group P had fully resolved in 86 % of patients , compared with 27 % in Group B ( P<0.001 ) . Median time to regression of sensory block to L4 was significantly shorter in Group P ( 97 min ) than in Group B ( 280 min ) ( P<0.001 ) . A clinical ly significant decrease in arterial pressure was more common in Group B ( 73 % ) than in Group P ( 32 % ) ( P=0.004 ) . Two patients in Group P required conversion to general anaesthesia , but for reasons unrelated to prilocaine itself . CONCLUSIONS The combination of prilocaine and fentanyl is a better alternative to that of low-dose bupivacaine and fentanyl , for spinal anaesthesia in ambulatory arthroscopic knee surgery IMPLICATION S A low-dose ( 4 mg ) , low-volume ( 0.8 mL ) , low-flow ( 2 min ) technique with hyperbaric bupivacaine toward the dependent side oriented injection and maintenance of the lateral decubitus position for 10 min produced selective spinal anesthesia with rapid recession of motor block and early discharge home Fifty‐four patients were studied prospect ively to evaluate home‐readiness after a small dose ( 1 or 2 ml ) of subarachnoid hyperbaric 0.5 % bupivacaine . The block regressed significantly earlier in the 1 ml group than in the 2 ml group ( p < 0.05 ) . The patients were also able to walk significantly earlier in the 1 ml group ( median 161 min and 231 min in the 1 ml and 2 ml groups , respectively ) ( p < 0.05 ) . However , there were no significant differences between the groups in time of ability to void . We conclude that adequate surgical anaesthesia can be achieved with small doses of hyperbaric bupivacaine used for spinal anaesthesia . Although the sensory and motor block after 1 or 2 ml hyperbaric bupivacaine recovered within a reasonable time for day‐case surgery , in some patients recovery of the ability to void was delayed to an undesirable extent BACKGROUND Hyperbaric solutions of ropivacaine have been used successfully to provide spinal anaesthesia . This study was design ed to compare the clinical efficacy of hyperbaric ropivacaine with that of the commercially available hyperbaric preparation of bupivacaine . METHODS Forty ASA grade I-II patients undergoing lower-abdominal , perineal or lower-limb surgery under spinal anaesthesia were recruited and r and omized to receive ropivacaine 5 mg ml(-1 ) ( with glucose 50 mg ml(-1 ) ) , 3 ml or bupivacaine 5 mg ml(-1 ) ( with glucose 80 mg ml(-1 ) ) , 3 ml . The level and duration of sensory block , intensity and duration of motor block , and time to mobilize and micturate were recorded . Patients were interviewed at 24 h and at 1 week to identify any residual problems . RESULTS All blocks were adequate for the proposed surgery , but there were significant differences between the two groups in mean time to onset of sensory block at T10 ( ropivacaine 5 min ; bupivacaine 2 min ; P<0.005 ) , median maximum extent ( ropivacaine T7 ; bupivacaine T5 ; P<0.005 ) and mean duration of sensory block at T10 ( ropivacaine 56.5 min ; bupivacaine 118 min ; P=0.001 ) . Patients receiving ropivacaine mobilized sooner ( ropivacaine mean 253.5 min ; bupivacaine 331 min ; P=0.002 ) and passed urine sooner ( ropivacaine mean 276 min ; bupivacaine 340.5 min ; P=0.01 ) than those receiving bupivacaine . More patients in the bupivacaine group required treatment for hypotension ( > 30 % decrease in systolic pressure ; P=0.001 ) . CONCLUSIONS Ropivacaine 15 mg in glucose 50 mg ml(-1 ) provides reliable spinal anaesthesia of shorter duration and with less hypotension than bupivacaine . The recovery profile for ropivacaine may be of interest given that more surgery is being performed in the day-case setting BACKGROUND The aim of this study was to compare spinal anesthesia effects of low-dose hyperbaric levobupivacaine and low-dose hyperbaric bupivacaine for transurethral procedures . METHODS In this double-blind , r and omized , controlled study , a total of 60 patients who were ASA I-III were r and omized into two groups . Group B received 7.5 mg hyperbaric bupivacaine plus 25 µg fentanyl , and Group L received 7.5 mg hyperbaric levobupivacaine plus 25 µg fentanyl intrathecally . The onset time to T10 dermatome , times to maximum sensory and motor block levels , time to two-segment regression of sensory block , time to Bromage score zero , time to full recovery of sensory block , and hemodynamic values , as well as adverse effects , were recorded . The primary outcome was the time to complete regression of motor block . RESULTS The onset time of block to T10 , time to maximum sensory block , and time to two-segment regression were similar in both groups . The time to maximum motor block was shorter in Group B ( 7 ± 3 min ) than in Group L ( 12±5 min ) , ( P<0.001 ) . The time to a Bromage score of zero ( recovery of motor block ) was shorter in Group L ( 105±19 min ) than in Group B ( 113±7 min ) , ( P=0.04 ) . The time to full recovery of sensory block was shorter in Group B ( 127±14 min ) than in Group L ( 157±34 min ) , ( P<0.001 ) . The requirement for analgesia was earlier in Group B ( 305±50 min ) than in Group L ( 389±146 min ) , ( P=0.004 ) . CONCLUSION Although both techniques provide adequate spinal block and have few similar side effects for transurethral surgery , the use of low-dose hyperbaric levobupivacaine plus fentanyl may be preferable to low-dose hyperbaric bupivacaine plus fentanyl because of the reduced motor block , shorter duration of motor block , longer duration of sensory block and longer time to the first requirement for analgesia |
2,304 | 26,800,168 | Dental implants at bone level show significantly less crestal bone change after 1 year of loading than tissue-level implants | PURPOSE The aim of this systematic review and meta- analysis was to evaluate crestal bone changes around implants when placing the implant-abutment connection at the crestal bone level or above . | BACKGROUND In the presence of a thin and narrow zone of gingival tissue root recessions caused by trauma or inflammatory reactions seem to be a common feature of the buccal tissue morphology . The surgical coverage is mainly indicated for aesthetic reasons and may be accomplished with pedicled flaps in conjunction with or without the use of connective tissue grafts . AIM The purpose of the present study was to evaluate the degree of vascularization of connective tissue grafts by applying a microsurgical approach . In addition , the clinical outcome was followed for 1 year . MATERIAL AND METHODS The study population consisted of 10 patients with bilateral Class I and II recessions at maxillary canines . In split-mouth design , the defects were r and omly selected for recession coverage either by a microsurgical ( test ) or macrosurgical ( control ) approach . Immediately after the surgical procedures , and after 3 and 7 days of healing , fluorescent angiograms were performed to evaluate graft vascularization . In addition , the clinical parameters were assessed before the surgical intervention , and 1 , 3 , 6 and 12 months postoperatively . RESULTS The results of the angiographic evaluation at test sites revealed a vascularization of 8.9+/-1.9 % immediately after the procedure . After 3 days and after 7 days , the vascularization rose to 53.3+/-10.5 % and 84.8+/-13.5 % , respectively . The corresponding vascularization at control sites were 7.95+/-1.8%/44.5+/-5.7 % and 64.0+/-12.3 % , respectively . All the differences between test and control sites were statistically significant . The clinical measurements revealed a mean recession coverage of 99.4+/-1.7 % for the test and 90.8+/-12.1 % for the control sites after the first month of healing . Again , this difference was statistically significant . The percentage of root coverage both test and control sites remained stable during the first year at 98 % and 90 % , respectively . CONCLUSIONS The present controlled clinical study has demonstrated that in root surface coverage , a microsurgical approach substantially improved the vascularization of the grafts and the percentages of root coverage compared with applying a conventional macroscopic approach The etiologic factors associated with crestal bone loss have not been comprehensively clarified . Several theories exist as to the reason for the observed changes in crestal bone height following implant restoration . In the 1990s , the wide-diameter implants were commercially introduced . Initially , the implants were restored with st and ard-diameter abutments because of lack of matching prosthetic components . Long-term radiographic follow-up of these ' platform-switched ' restored wide-diameter dental implants has demonstrated a smaller-than-expected vertical change in the crestal bone height around these implants that is typically observed around implants restored conventionally with prosthetic components of matching diameters . The aim of this r and omised controlled study was to assess radiographically marginal bone level alterations in implants restored according to the platform-switching concept compared with traditionally restored implants . Fifty-four subjects to participate in this r and omised controlled study were selected . Two groups were assigned at r and om : control group ( 56 implants were restored with st and ard matching-diameter abutments ) and test group ( 58 implants were restored with medialised abutments ) . X-ray explorations were taken for peri-implant bone level at the minute the last cementing of the prosthesis and at 1-year follow-up . NHI Image was used to digitally process and manipulate the radiographic images and perform the measurements . Mean of bone loss with platform-switching implants was -0·01 mm , and the mean of bone loss with st and ard platform implant was 0·42 mm . Outcomes of this study indicated that the platform-switching design could preserve the crestal bone levels to 1-year follow-up . There was a statistically significant difference in marginal bone loss PURPOSE To evaluate the influence of macro- and microstructure of the implant surface at the marginal bone level after functional loading . MATERIAL S AND METHODS Sixty-eight patients were r and omly assigned to 1 of 3 groups . The first group received 35 implants with a machined neck ( Ankylos ) ; the second group , 34 implants with a rough-surfaced neck ( Stage 1 ) ; and the third , 38 implants with a rough-surfaced neck with microthreads ( Oneplant ) . Clinical and radiographic examinations were conducted at baseline ( implant loading ) and 3 , 6 , and 12 months postloading . Two-way repeated analysis of variance ( ANOVA ) was used to test the significance of marginal bone change of each tested group at baseline , 3 , 6 , and 12 month follow-ups and 1-way ANOVA was also used to compare the bone loss of each time interval within the same implant group ( P < .05 ) . RESULTS At 12 months , significant differences were noted in the amount of alveolar bone loss recorded for the 3 groups ( P < .05 ) . The group with the rough-surfaced microthreaded neck had a mean crestal bone loss of 0.18 + /- 0.16 mm ; the group with the rough-surfaced neck , 0.76 + /- 0.21 mm ; and the group with the machined neck , 1.32 + /- 0.27 mm . In the rough-surfaced group and the rough-surfaced microthreaded group , no statistically significant changes were observed after 3 months , whereas the machined-surface group showed significant bone loss for every interval ( P < .05 ) . DISCUSSION To minimize marginal bone loss , in addition to the use of a rough surface at the marginal bone level , a macroscopic modification such as the addition of microthreads could be recommended . A rough surface and microthreads at the implant neck not only reduce crestal bone loss but also help with early biomechanical adaptation against loading in comparison to the machined neck design . CONCLUSION A rough surface with microthreads at the implant neck was the most effective design to maintain the marginal bone level against functional loading 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 PURPOSE Several long-term clinical studies have shown a mean marginal bone loss around dental implants of 1.5 to 2 mm in the first year after prosthetic restoration . Currently , concepts to avoid bone remodeling around dental implants have been developed . The use of prosthetic abutments with reduced width in relation to the implant diameter ( platform switching ) seems to have the greatest potential to limit the crestal resorption . The purpose of this clinical trial was to show that crestal bone height around dental implants could be influenced using a platform switch protocol and that the bone level would remain stable within 1 year after final prosthetic reconstruction . MATERIAL S AND METHODS Fifteen patients were treated with fixed implant retained prosthesis ; 14 wide-diameter implants were supplied with platform-switched abutments and served as the test group . Eight implants with regular diameter were reconstructed with traditional abutments and served as the control group . St and ardized digital radiographs were obtained for evaluation of the peri-implant bone levels at the time of installation of the final restoration and at 1-year follow-up . Marginal peri-implant bone levels were measured at the mesial and distal surfaces of each implant using digital image analysis . RESULTS The mean values of crestal bone height at baseline were -0.09 mm + /- 0.65 mm for the platform-switched implants and -1.73 mm + /- 0.46 mm for the nonplatform-switched implants . One year after final restoration , the mean value of crestal bone height was -0.22 mm + /- 0.53 mm for the test group and -2.02 mm + /- 0.49 mm for the control group . When tested with statistical means , the differences were significant for baseline and for follow-up ( P < /= .0001 ) . Mean bone level change from baseline to 1-year follow-up was -0.12 mm + /- 0.40 mm for the test group and -0.29 mm + /- 0.34 mm , respectively , for the control group . On analysis using ANCOVA , this difference was shown to be significant ( P < /= .0132 ) . CONCLUSION The concept of platform switching appears to limit crestal resorption and seems to preserve peri-implant bone levels . A certain amount of bone remodeling 1 year after final reconstruction occurs , but significant differences concerning the peri-implant bone height compared with the nonplatform-switched abutments are still evident 1 year after final restoration . The reduction of the abutment of 0.45 mm on each side ( 5 mm implant/4.1 mm abutment ) seems sufficient to avoid peri-implant bone loss PURPOSE To evaluate whether platform switching could preserve marginal bone around implants up to 6 months after loading . MATERIAL S AND METHODS 15 patients were selected for a r and omised controlled trial . Each patient received one customised wide body implant , with the external hex connection located eccentrically , allowing an extra 1 mm switch on one side . The hex was positioned at r and om at the mesial or distal side and the implant was loaded after 6 months of non-submerged healing . Patients were examined at 3 , 6 and 12 months after surgery , during which a radiograph was taken to evaluate bone levels . At 12 months , the mucosal thickness was measured using a perio-probe . RESULTS All implants survived and the mean overall bone loss , calculated from both the switched and non-switched side , was 0.39 mm ( SD 0.33 , range 0.00 - 1.45 ) , 0.85 mm ( SD 0.59 , range 0.10 - 2.50 ) and 0.80 mm ( SD 0.46 , 0.26 - 1.89 ) after 3 , 6 and 12 months , respectively . The bone loss continued up to 6 months but stabilised thereafter ( P = 0.615 ) . Significantly more bone loss was observed at the non-switched side compared to the switched side at 3 months ( 0.51 mm versus 0.28 mm , P = 0.019 ) , 6 months ( 1.05 mm versus 0.64 mm , P = 0.002 ) and 12 months ( 0.94 mm versus 0.66 mm , P = 0.002 ) . The mean mucosal thickness was 4.22 mm ( SD 1.45 ; range 1.50 - 7.00 ) , and was not significantly different between the switched and non-switched sides ( P = 0.882 ) . However , using a post-hoc analysis with the mean thickness as a threshold , the mean bone loss was only significantly different between switched and non-switched sides when the mucosa was thicker than 4.22 mm ( P = 0.036 ) . CONCLUSIONS The outcome of this r and omised trial is in accordance with earlier studies suggesting that that platform switching decreases bone loss by 30 % . Although the sample size was limited , it seems that the creation of a biologic width affects peri-implant bone loss to a significant extent and that platform switching is only effective when the mucosal thickness allows the establishment of a biologic width The aim of this study was to evaluate the change of marginal bone level radiographically around three different implant systems after 3 years in function . Fifty-four patients were included and r and omly assigned to three treatment groups of rough-surface implants ( TiUnite , n = 37 ) , hybrid of smooth and rough-surface implants ( Restore , n = 38 ) and rough surface with microthread implants ( Hexplant , n = 45 ) . Clinical and radiographic examinations were conducted at the time of implant loading ( baseline ) , 1 and 3 years after loading . A three-level mixed-effect analysis of covariance ( ancova ) was used to test the significance of the mean marginal bone change of the three implant groups . A total 120 of 135 implants completed the study . None of the implants failed to integrate . Significant differences were noted in the marginal bone loss recorded for the three groups ( P < 0.0001 ) . At 3 years , the rough surface with microthread implants had a mean crestal bone loss of 0.59 + /- 0.30 mm ; the rough-surface implants , 0.95 + /- 0.27 mm ; and the hybrid surface implants , 1.05 + /- 0.34 mm . Within the limitations of this study , rough-surface implants with microthread at the coronal part might have a long-term positive effect in maintaining the marginal bone level against functional loading in comparison with implants without these two features PURPOSE The purpose of this study was to evaluate the effectiveness of the platform-switching technique to prevent crestal bone loss following the restoration of dental implants . MATERIAL S AND METHODS This r and omized prospect i ve multicenter trial analyzed 60 partially edentulous adults recruited at 12 professional dental centers . Subjects were r and omly selected to receive either platform-enlarged or control cylindric implants in three different surgical procedures : conventional nonsubmerged , submerged , and submerged with a reduced abutment . The primary outcome measure was the change in crestal bone level assessed radiographically 12 and 24 months following placement . Nonparametric analysis of variance for repeated measures ( the Friedman test ) was used to assess the overall significance over time of the differences among implants in changes in crestal bone levels . Comparisons among and between groups of implants were performed by the nonparametric Friedman and Wilcoxon tests , respectively . In all the analyses an alpha = .05 was considered significant . RESULTS A total of 360 implants were placed ( 60 for each group ) . Three control implants failed during the 2nd year following placement . All submerged and 92 % of nonsubmerged platform-enlarged implants exhibited no bone loss . Control implants with an abutment as large as the implant platform exhibited more bone loss than their platform-enlarged counterparts ( P < .001 ) or control implants with a reduced abutment ( P < .001 ) . Submerged implants with an enlarged platform showed better crestal bone preservation than submerged control implants with a reduced abutment ( P = .06 ) . CONCLUSIONS The findings of the current trial indicated that the use of implants with an enlarged platform can result in better preservation of crestal bone as compared with conventional cylindric implants when a reduced abutment is mounted PURPOSE The aim of this clinical trial was to evaluate the influence of gingival tissue thickness on crestal bone loss around dental implants after a 1-year follow-up . MATERIAL S AND METHODS Forty-six implants ( 23 test and 23 control ) were placed in 19 patients . The test implants were placed about 2 mm supracrestally , whereas the control implants were positioned at the bone level . Before implant placement , the tissue thickness at implant sites was measured with a periodontal probe . After healing , metal-ceramic cement-retained prostheses were constructed . According to tissue thickness , the test implants were divided into A ( thin ) and B ( thick ) groups . Intraoral radiographs were performed and crestal bone changes were measured at implant placement and after 1 year . RESULTS Mean bone loss around the test implants in group A ( thin mucosa ) was 1.61 + /- 0.24 mm ( SE ; range , 0.9 to 3.3 mm ) on the mesial and 1.28 + /- 0.167 mm ( range , 0.8 to 2.1 mm ) on the distal . Mean bone loss in test group B ( thick mucosa ) implants was 0.26 + /- 0.08 mm ( range , 0.2 to 0.9 mm ) on the mesial aspect and 0.09 + /- 0.05 mm ( range , 0.2 to 0.6 mm ) on the distal aspect . Mean bone loss around control implants was 1.8 + /- 0.164 mm ( range , 0.6 to 4.0 mm ) and 1.87 + /- 0.166 mm ( range , 0.0 to 4.1 mm ) on the mesial and distal aspects , respectively . Analysis of variance revealed a significant difference in terms of bone loss between test A ( thin ) and B ( thick ) groups on both the mesial and the distal . CONCLUSION Initial gingival tissue thickness at the crest may be considered as a significant influence on marginal bone stability around implants . If the tissue thickness is 2.0 mm or less , crestal bone loss up to 1.45 mm may occur , despite a supracrestal position of the implant-abutment interface |
2,305 | 25,785,902 | Interventions transported to “ western ” countries showed comparable effects to trials in origin countries ; however , effects were stronger when interventions were transported to culturally more distant regions .
Effects were higher in countries with survival-focused family/childrearing values than those ranked more individualistic .
There were no differences in effects by country-level policy or re source factors .
Contrary to common belief , parenting interventions appear to be at least as effective when transported to countries that are more different culturally , and in service provision , than those in which they were developed .
Extensive adaptation did not appear necessary for successful transportation | There has been rapid global dissemination of parenting interventions , yet little is known about their effectiveness when transported to countries different from where they originated , or about factors influencing success .
This is the first systematic attempt to address this issue , focusing on interventions for reducing child behavior problems . | Findings are presented from an Icel and ic r and omized control trial ( RCT ) evaluating parent management training - Oregon model ( PMTO ™ ) , a parent training intervention design ed to improve parenting practice s and reduce child behavior problems . In a prior report from this effectiveness study that focused on child outcomes , children in the PMTO condition showed greater reductions in reported child adjustment problems relative to the comparison group . The present report focuses on observed parenting practice s as the targeted outcome , with risk by treatment moderators also tested . It was hypothesized that mothers assigned to the PMTO condition would show greater gains in pre-post parenting practice s relative to controls . The sample was recruited from five municipalities throughout Icel and and included 102 participating families of children with behavior problems . Cases were referred by community professionals and r and omly assigned to either PMTO ( n = 51 ) or community services usually offered ( n = 51 ) . Child age ranged from 5 to 12 years ; 73 % were boys . Contrary to expectations , findings showed no main effects for changes in maternal parenting . However , evaluation of risk by treatment moderators showed greater gains in parenting practice s for mothers who increased in depressed mood within the PMTO group relative to their counterparts in the comparison group . This finding suggests that PMTO prevented the expected damaging effects of depression on maternal parenting . Failure to find hypothesized main effects may indicate that there were some unobserved factors regarding the measurement and a need to further adapt the global observational procedures to Icel and ic culture BACKGROUND There is a pressing need for cost-effective population -based interventions to tackle early-onset antisocial behaviour . As this is determined by many factors , it would seem logical to devise interventions that address several influences while using an efficient means of delivery . The aim of this trial was to change four risk factors that predict poor outcome : ineffective parenting , conduct problems , attention deficit/hyperactivity disorder ( ADHD ) symptoms , and low reading ability . METHODS A r and omised controlled trial was carried out in eight schools in London , Engl and . Nine hundred and thirty-six ( 936 ) 6-year-old children were screened for antisocial behaviour , then parents of 112 high scorers were r and omised to parenting groups held in schools or control ; 109 were followed up a year later . The intervention lasted 28 weeks and was novel as it had components to address both child behaviour ( through the Incredible Years programme ) and child literacy ( through a new ' SPOKES ' programme to help parents read with their children ) . Fidelity of implementation was emphasised by careful training of therapists and weekly supervision . Controls received an information helpline . Assessment of conduct problems was by parent interview , parenting by direct observation and child reading by psychometric testing . RESULTS At follow-up parents allocated to the intervention used play , praise and rewards , and time out more often than controls , and harsh discipline less ; effect sizes ranged from .31 to .59 sd ( p-values .046 to .005 ) . Compared to control children , whose behaviour did n't change , intervention children 's conduct problems reduced by .52sd , ( p < .001 ) , dropping from the 80th to the 61st percentile ; oppositional-defiant disorder ( ODD ) halved from 60 % to 31 % ( p = .003 ) . ADHD symptoms reduced by .44sd ( p = .002 ) , and reading age improved by six months ( .36sd , p = .027 ) . Teacher-rated behaviour did n't change . The programme cost pound2,380 ( $ 3,800 ) per child . CONCLUSIONS Effective population -based early intervention to improve the functioning of with antisocial behaviour is practically feasible by targeting multiple risk factors and emphasising implementation fidelity Structured parent training has been proven to be effective in reducing disruptive behavior problems ( DBP ) in children . Most of the programs that are used in Sweden have their origin in North America , and there is an ongoing debate over the transferability to Sweden of manual-based programs developed in other context s. The goal of the present study was to study effectiveness of the Incredible Years parent-training program ( IY ) , developed in the US , in regular clinical work in Sweden , using a r and omized controlled design . Parents of 62 four to eight-year-old children diagnosed with Oppositional Defiant Disorder participated in the study . Parents of 38 children were assigned to parent training ( PT ) and 24 to a waiting list ( WL ) . The results indicate that the IYS retains the positive effects on children 's disruptive behavior problems when translated and transferred to Swedish . There was a statistically significant difference in reduction of DBP in children between the groups in favor of the PT . The improvement in the PT group was sustained at the one-year follow-up . The improvement also , at least to some extent , generalized over time to the school context . There was also a statistically significant difference in mothers ' report of pre to post change in parenting alliance between the PT and WL groups . The IYS program was appreciated and well received by the participating mothers This study was a r and omized control trial ( RCT ) of Parent Management Training -- The Oregon Model ( PMTO ) in Norway . A sample representing all health regions of Norway and consisting of 112 children with conduct problems and their families participated in the study . Families were r and omly assigned to either PMTO or a regular services comparison group . PMTO was delivered via existing children 's services , and families were recruited using the agencies ' regular referral procedures , making this the first effectiveness study of PMTO and the first RCT of PMTO conducted outside of the United States . Using a multiagent-multi method approach , results showed that PMTO was effective in reducing parent-reported child externalizing problems , improving teacher-reported social competence , and enhancing parental discipline . Age level and gender modified the effects of PMTO treatment on other outcomes . In a path model , participation in PMTO was associated with improved parental discipline , and effective discipline predicted greater child compliance , fewer child-initiated negative chains , and lower levels of child externalizing problems . Findings are presented along with a discussion of the implication s for practice and research and the challenges accompanying effectiveness trials The present study evaluated the effectiveness of the Positive Parenting Program ( Triple P ) with a sample of Chinese parents of children with early onset conduct-related problems in Hong Kong . The participants consisted of 91 parents whose children attended maternal and child health centers and child assessment centers for service , and were between three to seven years old . Participants were r and omly assigned to the intervention ( TP ) and a waitlist control group ( WL ) . There was no significant difference in pre-intervention measures between the two groups . However , at post intervention , participants in the TP group reported significantly lower levels of child behavior problems , lower dysfunctional parenting styles , and higher parent sense of competence , compared to the WL group . Implication s of these findings for the use of Triple P with families of Chinese descent are discussed BACKGROUND To test effectiveness of a parenting intervention , delivered in a community-based voluntary-sector organisation , for reducing conduct problems in clinical ly-referred children . METHODS R and omised controlled trial , follow-up at 6 , 18 months , assessors blind to treatment status . Participants --76 children referred for conduct problems , aged 2 - 9 , primarily low-income families , r and omised to treatment vs. 6-month wait-list group . Retention was 93 % at 6 months , 90 % at 18 months . Interventions --Webster-Stratton Incredible Years video-based 14-week group programme , teaches cognitive-behavioural principles for managing behaviour , using a collaborative , practical , problem-solving approach . Primary outcomes --child problem behaviour by parent-report ( Eyberg ) and home-based direct observation ; secondary outcomes --observed positive and negative parenting ; parent-reported parenting skill , confidence and depression . RESULTS Post-treatment improvements were found in child problem behaviour , by parent-report ( effect size ( ES ) .48 , p = .05 ) and direct observation ( ES .78 , p = .02 ) ; child independent play ( ES .77 , p = .003 ) ; observed negative ( ES .74 , p = .003 ) and positive ( ES .38 , p = .04 ) parenting ; parent-reported confidence ( ES .40 , p = .03 ) and skill ( ES .65 , p = .01 ) , using ANCOVA to control for baseline scores . Maternal depression did not change . Consumer satisfaction was high . At 18-month follow-up , although no r and omised comparison was possible , changes appeared to maintain , with no significant change toward baseline level on any measure . Change in observed positive parenting appeared to mediate change in child problem behaviour ( p < .025 ) . CONCLUSIONS Findings suggest that a group-based cognitive-behavioural parenting programme , delivered by well-trained and supervised staff , can be effective in a community voluntary-sector setting , for reducing conduct problems and enhancing parenting skills . Change in parenting skill appears to be a key mechanism for change in child behaviour . Findings have implication s for feasibility of translating evidence -based programmes , even for clinical ly-referred conduct problems , into less specialised community setting s , likely to have lower costs and be more accessible for families Objective To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder . Design Pragmatic r and omised controlled trial using a block design with allocation by area . Setting Eleven Sure Start areas in north and mid-Wales . Participants 153 parents from socially disadvantaged areas , with children aged 36 - 59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory . Participants were r and omised on a 2:1 basis , 104 to intervention and 49 to remaining on the wait listing ( control ) . Twenty ( 13 % ) were lost to follow-up six months later , 18 from the intervention group . Intervention The Webster-Stratton Incredible Years basic parenting programme , a 12 week group based intervention . Main outcome measures Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home . Parents ' self reported parenting competence , stress , and depression . St and ardised and well vali date d instruments were used throughout . Results At follow-up , most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group . The intention to treat analysis for the primary outcome measure , the Eyberg child behaviour inventory , showed a mean difference between groups of 4.4 points ( 95 % confidence interval 2.0 to 6.9 , P<0.001 ) on the problem scale with an effect size of 0.63 , and a mean difference of 25.1 ( 14.9 to 35.2 , P<0.001 ) on the intensity scale with an effect size of 0.89 . Conclusion This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff . It has influenced policy within Wales and provides lessons for Engl and where , to date , Sure Start programmes have not been effective . Trial registration IS RCT This article reports the effectiveness of two universal prevention programs in reducing externalizing behavior in elementary school children . A sample of 1,675 first grade rs in 56 Swiss elementary schools was r and omly assigned to a school-based social competence intervention , a parental training intervention , both , or control . Externalizing psychopathology and social competence ratings were provided by the children , primary caregivers , and teachers at the beginning and end of the 2-year program , with a follow-up 2 years later . Intention-to-treat analyses revealed that long-term effects on teacher- and parent-rated externalizing behavior were greater for the social competence intervention than for the control . However , for most outcomes , no statistically significant positive effects were observed This r and omized clinical trial assessed the effectiveness of multisystemic therapy ( MST ) for 156 youths who met the diagnostic criteria for conduct disorder . Sweden 's 3 largest cities and 1 small town served as the recruiting area for the study . A mixed factorial design was used , with r and om allocation between MST and treatment as usual groups . Assessment s were conducted at intake and 7 months after referral . With an intention-to-treat approach , results from multiagent and multi method assessment batteries showed a general decrease in psychiatric problems and antisocial behaviors among participants across treatments . There were no significant differences in treatment effects between the 2 groups . The lack of treatment effect did not appear to be caused by site differences or variations in program maturity . MST treatment fidelity was lower than that of other studies , although not clearly related to treatment outcomes in this study . The results are discussed in terms of differences between Sweden and the United States . One difference is the way in which young offenders are processed ( a child welfare approach vs. a juvenile justice system approach ) . Sociodemographic differences ( e.g. , rates of poverty , crime , and substance abuse ) between the 2 countries may also have moderating effects on the rates of rehabilitation among young offenders . ( PsycINFO Data base Record ( c ) 2008 APA , all rights reserved ) This study evaluates the initial efficacy of the Parent-Child Interaction Therapy ( PCIT ) for Puerto Rican preschool children aged 4 - 6 years with a diagnosis of attention-deficit/hyperactivity disorder ( ADHD ) , combined or predominantly hyperactive type , and significant behavior problems . Thirty-two families were r and omly assigned to PCIT ( n = 20 ) or a 3.5-month waiting-list condition ( WL ; n = 12 ) . Participants from both groups completed pretreatment and posttreatment assessment s. Outcome measures included child 's ADHD symptoms and behavior problems , parent or family functioning , and parents ' satisfaction with treatment . ANCOVAs with pretreatment measures entered as covariates were significant for all posttreatment outcomes , except mother 's depression , and in the expected direction ( p < .01 ) . Mothers reported a highly significant reduction in pretreatment hyperactivity and inattention and less aggressive and oppositional-defiant behaviors , conduct problems assessed as problematic , parenting stress associated with their child 's behavior , and an increase in the use of adequate parenting practice s. For the WL group , there were no clinical ly significant changes in any measure . Treatment gains obtained after treatment were maintained at a 3.5-month follow-up assessment . PCIT seems to be an efficacious intervention for Puerto Rican families who have young children with significant behavior problems The effectiveness of the Incredible Years Parenting Program was evaluated in a low-income sample of Caucasian , African American , Hispanic , and Asian mothers whose children were enrolled in Head Start . Data from two prior intervention studies [ Webster-Stratton ( 1998 ) Journal of Consulting and Clinical Psychology , 66(5 ) , 715–730 ; Webster-Stratton et al. ( in press ) Journal of Clinical Child Psychology ] were combined , yielding a sample of 634 families ( 370 Caucasian , 120 African American , 73 Asian , 71 Hispanic ) across 23 Head Start centers . Centers were matched and assigned r and omly to either an experimental condition ( 8–12 weeks of weekly 2-hr parenting classes ) , or a control condition ( the regular Head Start Program without parenting groups ) . Families in both conditions were assessed using home observations of parent – child interactions and parent reports of parenting style and discipline strategies and child behavior problems in the fall ( baseline ) and spring ( postintervention ) of the children 's Head Start year . Families were reassessed 1 year later . Following treatment , intervention mothers were observed to be more positive , less critical , more consistent , and more competent in their parenting than were control mothers . Additionally , children of intervention parents were observed to exhibit fewer behavior problems than were control children . Differences in treatment response across ethnic groups were few , and did not exceed the number expected by chance . Parents from all groups reported high satisfaction levels following the parenting program . Results indicate that the Incredible Years Program is accepted by and effective with diverse population Abstract Objective : To see whether a behaviourally based group parenting programme , delivered in regular clinical practice , is an effective treatment for antisocial behaviour in children . Design : Controlled trial with permuted block design with allocation by date of referral . Setting : Four local child and adolescent mental health services . Participants : 141 children aged 3 - 8 years referred with antisocial behaviour and allocated to parenting groups ( 90 ) or waiting list control ( 51 ) . Intervention : Webster-Stratton basic videotape programme administered to parents of six to eight children over 13 - 16 weeks . This programme emphasises engagement with parental emotions , rehearsal of behavioural strategies , and parental underst and ing of its scientific rationale . Main outcome measures : Semistructured parent interview and question naires about antisocial behaviour in children administered 5 - 7 months after entering trial ; direct observation of parent-child interaction . Results : Referred children were highly antisocial ( above the 97th centile on interview measure ) . Children in the intervention group showed a large reduction in antisocial behaviour ; those in the waiting list group did not change ( effect size between groups 1.06 SD ( 95 % confidence interval 0.71 to 1.41 ) , P<0.001 ) . Parents in the intervention group increased the proportion of praise to ineffective comm and s they gave their children threefold , while control parents reduced it by a third ( effect size between groups 0.76 ( 0.16 to 1.36 ) , P=0.018 ) . If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16 % . Conclusions : Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions . Follow up is needed to see if the children 's poor prognosis is improved and criminality prevented . What is already known on this topic Children who persistently display a high level of antisocial behaviour are at high risk of social rejection , juvenile delinquency , and long term unemployment ; the cost to society is high While some behaviourally based parenting programmes have been shown to be effective in university centre trials with volunteers or specially selected cases , most trials of psychological treatments for children in real life setting s have shown no effect What this study adds An evidence based intervention is available for use in regular clinical practice that effectively reduces antisocial behaviour in referred children The intervention works well with children at risk of criminality from a combination of highly antisocial behaviour , multiple psychopathology , and social We examined mediators and moderators of change in conduct problems , in a multiagency r and omized trial of the Incredible Years parenting program . Preschoolers ( n = 153 ) at risk for conduct problems were r and omly assigned to intervention ( n = 104 ) and wait-list ( n = 49 ) groups . Boys and younger children , and those with more depressed mothers , tended to show greater improvement in conduct problems post-intervention . Other risk factors ( i.e. , teen or single parenthood , very low income , high initial levels of problem behavior ) showed no predictive effects , implying intervention was at least as successful at helping the most disadvantaged families , compared to more advantaged . Mediator analyses found change in positive parenting skill predicted change in conduct problems OBJECTIVE Antisocial personality is a common adult problem that imposes a major public health burden , but for which there is no effective treatment . Affected individuals exhibit persistent antisocial behavior and pervasive antisocial character traits , such as irritability , manipulativeness , and lack of remorse . Prevention of antisocial personality in childhood has been advocated , but evidence for effective interventions is lacking . METHOD The authors conducted two follow-up studies of r and omized trials of group parent training . One involved 120 clinic-referred 3- to 7-year-olds with severe antisocial behavior for whom treatment was indicated , 93 of whom were reassessed between ages 10 and 17 . The other involved 109 high-risk 4- to 6-year-olds with elevated antisocial behavior who were selectively screened from the community , 90 of whom were reassessed between ages 9 and 13 . The primary psychiatric outcome measures were the two elements of antisocial personality , namely , antisocial behavior ( assessed by a diagnostic interview ) and antisocial character traits ( assessed by a question naire ) . Also assessed were reading achievement ( an important domain of youth functioning at work ) and parent-adolescent relationship quality . RESULTS In the indicated sample , both elements of antisocial personality were improved in the early intervention group at long-term follow-up compared with the control group ( antisocial behavior : odds ratio of oppositional defiant disorder=0.20 , 95 % CI=0.06 , 0.69 ; antisocial character traits : B=-4.41 , 95 % CI=-1.12 , -8.64 ) . Additionally , reading ability improved ( B=9.18 , 95 % CI=0.58 , 18.0 ) . Parental expressed emotion was warmer ( B=0.86 , 95 % CI=0.20 , 1.41 ) and supervision was closer ( B=-0.43 , 95 % CI=-0.11 , -0.75 ) , but direct observation of parenting showed no differences . Teacher-rated and self-rated antisocial behavior were unchanged . In contrast , in the selective high-risk sample , early intervention was not associated with improved long-term outcomes . CONCLUSIONS Early intervention with severely antisocial children for whom treatment is indicated may prevent the development of antisocial personality in adolescence and may improve academic performance . In contrast , early intervention with selective high-risk sample s may be ineffective |
2,306 | 29,702,128 | The meta- analysis revealed that interventions implementing repeated taste exposure had better pooled effects than those which did not .
Intake increased with number of taste exposures and intake was greater when vegetables offered were in their plain form rather than paired with a flavor , dip or added energy ( e.g. oil ) .
Moreover , intake of vegetables which were unfamiliar/disliked increased more than those which were familiar/liked .
Repeated taste exposure is a simple technique that could be implemented in childcare setting s and at home by parents . | BACKGROUND Most children do not meet daily recommendations for fruit and vegetable intake , and consumption of vegetables remains especially low .
Eating habits track from childhood to adulthood hence establishing liking and intake of vegetables is important .
OBJECTIVE To identify the most successful strategies to enhance vegetable intake in preschool children aged 2 - 5 years . | OBJECTIVE Determine whether Color Me Healthy ( CMH ) , an interactive nutrition and physical activity program for preschool children , increases fruit and vegetable consumption . DESIGN Intervention study . Data were collected at baseline , 1 week post-intervention , and 3 months post-intervention . SETTING Child care centers . PARTICIPANTS Preschool children ( n = 263 ) in 17 child care centers . INTERVENTION Child care centers were r and omly assigned to 1 of 2 conditions ; children ( n = 165 ) in 10 centers received the CMH curriculum , and children ( n = 98 ) in 7 centers acted as comparisons and did not receive the curriculum . MAIN OUTCOME MEASURES Process and outcome evaluation . Consumption of fruit and vegetable snacks . ANALYSIS Data were analyzed using repeated- measures analysis of variance and hierarchical linear modeling . RESULTS Children who received CMH significantly increased their consumption of fruit snacks by approximately 20.8 % and vegetable snacks by approximately 33.1 % between baseline assessment and the assessment conducted 3 months after the completion of the CMH program . Hierarchical linear modeling determined that group assignment ( ie , CMH or control ) was the only significant predictor of fruit and vegetable consumption . CONCLUSIONS AND IMPLICATION S Findings suggest that CMH may be used in child care setting s for developing healthful eating habits Background Governments worldwide recommend daily consumption of fruit and vegetables . We examine whether this benefits health in the general population of Engl and . Methods Cox regression was used to estimate HRs and 95 % CI for an association between fruit and vegetable consumption and all-cause , cancer and cardiovascular mortality , adjusting for age , sex , social class , education , BMI , alcohol consumption and physical activity , in 65 226 participants aged 35 + years in the 2001–2008 Health Surveys for Engl and , annual surveys of nationally representative r and om sample s of the non-institutionalised population of Engl and linked to mortality data ( median follow-up : 7.7 years ) . Results Fruit and vegetable consumption was associated with decreased all-cause mortality ( adjusted HR for 7 + portions 0.67 ( 95 % CI 0.58 to 0.78 ) , reference category < 1 portion ) . This association was more pronounced when excluding deaths within a year of baseline ( 0.58 ( 0.46 to 0.71 ) ) . Fruit and vegetable consumption was associated with reduced cancer ( 0.75 ( 0.59–0.96 ) ) and cardiovascular mortality ( 0.69 ( 0.53 to 0.88 ) ) . Vegetables may have a stronger association with mortality than fruit ( HR for 2 to 3 portions 0.81 ( 0.73 to 0.89 ) and 0.90 ( 0.82 to 0.98 ) , respectively ) . Consumption of vegetables ( 0.85 ( 0.81 to 0.89 ) per portion ) or salad ( 0.87 ( 0.82 to 0.92 ) per portion ) were most protective , while frozen/canned fruit consumption was apparently associated with increased mortality ( 1.17 ( 1.07 to 1.28 ) per portion ) . Conclusions A robust inverse association exists between fruit and vegetable consumption and mortality , with benefits seen in up to 7 + portions daily . Further investigations into the effects of different types of fruit and vegetables are warranted BACKGROUND The use of rewards to encourage children to eat healthily is controversial . However , research er-led interventions have shown that incentives combined with taste exposure can increase both intake and liking . To date , this has not been tested in the home setting . OBJECTIVES The objectives were to test the hypothesis that parent-administered repeated taste exposures to an initially disliked vegetable combined with reward will increase children 's liking and intake and to compare the effects of tangible and social rewards . DESIGN In this r and omized controlled trial , families with children aged 3 - 4 y ( n = 173 ) were r and omly assigned to exposure + tangible reward ( sticker ) , exposure + social reward ( praise ) , or no-treatment control conditions after a pretest assessment in which a target vegetable was selected for each child . In the intervention groups , parents offered their children 12 daily tastes of the vegetable , giving either praise or a sticker for tasting . No specific advice was given to the control group . Assessment s of intake and liking of the target vegetable were conducted by research ers immediately after the intervention period and 1 and 3 mo later . RESULTS Children who received exposure + tangible rewards increased their intake ( P = 0.001 ) and liking ( P = 0.001 ) of their target vegetable significantly more than did children in the control group . Differences were maintained at the 3-mo follow-up ( intake : P = 0.005 ; liking : P = 0.001 ) . Increases in intake and liking in the exposure + social reward group were not significantly different from the control group . CONCLUSION The findings of this home-based study support parental use of tangible rewards with repeated taste exposures to improve children 's diets . This trial is registered as IS RCT N42922680 Background Mexico has the highest adult overweight and obesity prevalence in the Americas ; 23.8 % of children < 5 years old are at risk for overweight and 9.7 % are already overweight or obese . Creciendo Sanos was a pilot intervention to prevent obesity among preschoolers in Instituto Mexicano del Seguro Social ( IMSS ) clinics . Methods We r and omized 4 IMSS primary care clinics to either 6 weekly educational sessions promoting healthful nutrition and physical activity or usual care . We recruited 306 parent-child pairs : 168 intervention , 138 usual care . Children were 2 - 5 years old with WHO body mass index ( BMI ) z-score 0 - 3 . We measured children ’s height and weight and parents reported children ’s diet and physical activity at baseline and 3 and 6-month follow-up . We analyzed behavioral and BMI outcomes with generalized mixed models incorporating multiple imputation for missing values . Results 93 ( 55 % ) intervention and 96 ( 70 % ) usual care families completed 3 and 6-month follow-up . At 3 months , intervention v. usual care children increased vegetables by 6.3 servings/week ( 95 % CI , 1.8 , 10.8 ) . In stratified analyses , intervention participants with high program adherence ( 5 - 6 sessions ) decreased snacks and screen time and increased vegetables v. usual care . No further effects on behavioral outcomes or BMI were observed . Transportation time and expenses were barriers to adherence . 90 % of parents who completed the post-intervention survey were satisfied with the program . Conclusions Although satisfaction was high among participants , barriers to participation and retention included transportation cost and time . In intention to treat analyses , we found intervention effects on vegetable intake , but not other behaviors or BMI .Trial registration Clinical Trials.gov NCT01539070.Comisión Nacional de Investigación Científica del IMSS : 2009 - 785 - 120 OBJECTIVE To measure the effects of two school-based interventions on children 's intake of fruit and vegetables ( F&V ) . DESIGN AND METHODS A total of six primary schools were r and omly assigned to ( 1 ) a free F&V distribution programme , or ( 2 ) a multicomponent programme , consisting of a classroom curriculum and parental involvement . The two interventions were evaluated on their effects and compared with six control schools in a pre-test-post-test design . Two methods were used for dietary assessment : a pre-structured food recall and a food-frequency question naire including only F&V. SUBJECTS A total of 939 parents of children aged 4 - 12 years filled out the question naire at both pre-test and post-test . The response rate was 54 % . RESULTS Multilevel analyses showed that both programmes were equally effective in increasing children 's fruit consumption by 0.2 portions per day . The free F&V distribution increased vegetable intake among non-native children and the oldest age group , and the multicomponent programme among the oldest children and girls . The distribution also caused an increased 24 h fruit , juice and vegetable intake among the youngest and the oldest age groups , and the multicomponent programme among all children . CONCLUSION The results of this study indicate that both interventions were shown to be effective for different subgroups regarding age , gender and ethnicity . When comparing both interventions , the distribution programme was shown to be more effective , especially in increasing vegetable consumption . An important next step will be to investigate which intervention has the greatest potential to be implemented in primary schools BACKGROUND Evidence -based strategies for promoting vegetable consumption among children are limited . OBJECTIVE To determine the effects of providing a palatable “ dip ” along with repeated exposure to a raw vegetable on preschoolers ' liking and intake . PARTICIPANTS One hundred fifty-two predominately Hispanic preschool-aged children studied in Head Start classrooms in 2008 . DESIGN A between-subjects , quasiexperimental design was used . A moderately-liked raw vegetable ( broccoli ) was offered twice weekly at afternoon snacks for 7 weeks . Classrooms were r and omized to receive broccoli in one of four conditions differing in the provision of dip . Bitter taste sensitivity was assessed using 6-n-propylthiouracil . INTERVENTION Broccoli was provided in four conditions : with regular salad dressing as a dip , with a light ( reduced energy/fat ) version of the dressing as a dip , mixed with the regular dressing as a sauce , or plain ( without dressing ) . MAIN OUTCOME MEASURES Mean broccoli intake during 7 weeks of exposure and broccoli liking following exposure . STATISTICAL ANALYSES Descriptive statistics were generated . Multilevel models for repeated measures tested effects of condition and bitter sensitivity on mean broccoli intake during exposure and on pre- and post-exposure liking while adjusting for classroom effects and potential covariates . RESULTS The majority of Hispanic preschoolers ( 70 % ) showed sensitivity to the bitter taste of 6-n-propylthiouracil . Children 's broccoli liking increased following exposure but did not vary by dip condition or bitter sensitivity . Bitter-sensitive children , however , ate 80 % more broccoli with dressing than when served plain ( P<0.001 ) ; effects did vary based on whether regular or light dressing was provided as a dip or sauce . Dip did not promote broccoli intake among bitter-insensitive children . CONCLUSIONS Providing dip — regular , light , or as a sauce — increased raw broccoli intake among bitter-sensitive Hispanic preschoolers . Findings suggest that offering low-fat dips can promote vegetable intake among some children who are sensitive to bitter tastes Children 's consumption of vegetables is still below recommendations . Since preference is the most important predictor of children 's intake and most children dislike vegetables , new strategies are needed to increase their preferences for vegetables . Flavour nutrient learning ( FNL ) could be an effective mechanism to change preferences . Forty healthy toddlers were included in a r and omized intervention study . During an intervention period of 7weeks , they consumed vegetable soups ( endive and spinach ) twice per week . Half of the group received a high-energy variant of one soup ( e.g. HE spinach ) and a low energy variant of the other ( LE endive ) , whereas for the other half the order was reversed ( HE endive , LE spinach ) . Primary outcome measures were preference and ad libitum consumption ( with a maximum of 200 g ) of both vegetable products ( LE ) , measured before , shortly after the intervention period , and 2 and 6months following conditioning to assess longer-term effects . After completion of the intervention period , 28 children ( 14 girls and 14 boys , age 35months ; SD±8.3 ) met criteria for FNL to occur , and were included in further data analysis . Results showed a significant increase ( ~58 g ) in ad libitum intake for both vegetable soups ( stable over time ) , but irrespective of the energy content . This indicates a robust effect of mere exposure on intake , but no FNL . For preference , however , results showed a significant shift in liking for the vegetable soup consistently paired with high energy , supporting FNL Children are not consuming sufficient amounts of fruits and vegetables in their habitual diet . Methods derived from associative learning theories could be effective at promoting vegetable intake in pre-school children . The objective of the present study was to compare the effectiveness of different learning strategies in promoting the intake of a novel vegetable . Children aged between 9 and 38 months were recruited from UK nurseries . The children ( n 72 ) were r and omly assigned to one of three conditions ( repeated exposure , flavour-flavour learning or flavour-nutrient learning ) . Each child was offered ten exposures to their respective version of a novel vegetable ( artichoke ) . Pre- and post-intervention measures of artichoke purée and carrot purée ( control vegetable ) intake were taken . At pre-intervention , carrot intake was significantly higher than artichoke intake ( P<0·05 ) . Intake of both vegetables increased over time ( P<0·001 ) ; however , when changes in intake were investigated , artichoke intake increased significantly more than carrot intake ( P<0·001 ) . Artichoke intake increased to the same extent in all three conditions , and this effect was persistent up to 5 weeks post-intervention . Five exposures were sufficient to increase intake compared to the first exposure ( P<0·001 ) . Repeated exposure to three variants of a novel vegetable was sufficient to increase intake of this vegetable , regardless of the addition of a familiar taste or energy . Repetition is therefore a critical factor for promoting novel vegetable intake in pre-school children Background Strategies to increase fruit and vegetable consumption of preschool aged children are needed . Objectives Evaluate the independent effects of the following meal service strategies on intake of fruits and vegetables of preschool children : 1 . ) Serving fruits and vegetables in advance of other menu items as part of traditional family style meal service ; and 2 . ) Serving meals portioned and plated by providers . Methods Fifty-three preschool aged children completed a r and omized crossover experiment conducted at a Head Start center in Minneapolis , MN . Over a six week trial period each of the experimental meal service strategies ( serving fruits and vegetable first and serving meals portioned by providers ) was implemented during lunch service for two one-week periods . Two one-week control periods ( traditional family style meal service with all menu items served at once ) were also included over the six week trial period . Childrens lunch intake was observed as a measure of food and nutrient intake during each experimental condition . Results Fruit intake was significantly higher ( p<0.01 ) when fruits and vegetables were served in advance of other meal items ( 0.40 servings/meal ) compared to the traditional family style meal service control condition when they were served in t and em with other menu items ( 0.32 servings/meal ) . Intakes of some nutrients found in fruits ( vitamin A and folate ) were concomitantly higher . In contrast , fruit and vegetable intakes were significantly lower and energy intake significantly higher during the provider portioned compared with control condition . Conclusions Serving fruits in advance of other meal items may be a low cost easy to implement strategy for increasing fruit intake in young children . However , serving vegetables first does not appear to increase vegetable intake . Results provide support for current recommendations for traditional family style meal service in preschool setting BACKGROUND Vegetable consumption among preschool children is below recommended levels . New evidence -based approaches to increase preschoolers ' vegetable intake , particularly in the child care setting , are needed . This study tests the effectiveness of two community-based r and omized interventions to increase vegetable consumption and willingness to try vegetables : ( 1 ) the pairing of a vegetable with a familiar , well-liked food and ( 2 ) enhancing the visual appeal of a vegetable . METHODS Fifty-seven preschoolers enrolled in a Child and Adult Care Food Program-participating child care center participated in the study ; complete lunch and snack data were collected from 43 and 42 children , respectively . A within-subjects , r and omized design was used , with order of condition counterbalanced . For lunch , steamed broccoli was served either on the side of or on top of cheese pizza . For a snack , raw cucumber was served either as semicircles with chive and an olive garnish or arranged in a visually appealing manner ( in the shape of a caterpillar ) . Paired t-tests were used to determine differences in consumption of meal components , and McNemar 's test was performed to compare willingness to taste . RESULTS Neither visual appeal enhancement nor pairing with a liked food increased vegetable consumption . Pairing increased willingness to try the vegetable from 79 % to 95 % of children ( p=0.07 ) . Greater vegetable intake occurred at snack than at lunch . CONCLUSIONS Further research should explore the strategy of pairing vegetables with liked foods . Greater consumption at snack underscores snack time as a critical opportunity for increasing preschool children 's vegetable intake Background Repeated taste exposure , in combination with small rewards , has been shown to increase children 's acceptance of disliked foods . However , previous studies have used direct contact with research ers or professionals for the implementation of the repeated exposure procedure . If mailed taste exposure instructions to parents produced comparable outcomes , this could be a cost-effective and easily disseminable strategy to promote healthier diets in children . Objective Our r and omized controlled study aim ed to test the efficacy and acceptability of mailed material s giving instructions on taste exposure as a means of increasing acceptance of vegetables in preschool-aged children . Design Participants were families of 3-year-old twins from the Gemini cohort who took part between March 2011 and April 2012 . Families were r and omized to a mailed intervention or a no treatment control condition . The intervention involved offering each child 14 daily tastes of a disliked ( target ) vegetable with a small reward ( a sticker ) if the child complied . Main outcome measures Outcomes were the child 's intake of the target vegetable ( number of pieces ) and parent reports of the child 's liking at two baseline ( T1 and T2 ) and one postintervention ( T3 ) behavior assessment . Results Record sheets with intake and liking data from T1 , T2 , and T3 were returned for 472 children , of which 442 were complete ( 94 % ) . Over the intervention period ( T2 to T3 ) intake and liking of the target vegetable increased significantly more in the intervention group than in the control group ( intake : odds ratio 12.05 , 95 % CI 8.05 to 18.03 , P<0.001 ; liking : odds ratio 12.34 , CI 7.97 to 19.12 , P<0.001 ) . Acceptability of the procedure was very high among parents who completed the protocol . Conclusions Mailed instructions for taste exposure were effective in increasing children 's acceptance of an initially disliked vegetable . These results support the value of parent-administered exposure to increase children 's vegetable acceptance , and suggest that it can be carried out without direct health professional contact BACKGROUND Behavioral economics and psychology have been applied to altering food choice , but most studies have not measured food intake under free-living conditions . OBJECTIVES To test the effects of a strategy that pairs positive stimuli ( ie , stickers and cartoon packaging ) with vegetables and presents them as the default snack . DESIGN A r and omized controlled trial was conducted with children who reported consumption of fewer than two servings of vegetables daily . Children ( aged 3 to 5 years ) in both control ( n=12 ) and treatment ( n=12 ) groups received a week 's supply of plainly packaged ( ie , generic ) vegetables , presented by parents as a free choice with an alternative snack ( granola bar ) , during baseline ( Week 1 ) and follow-up ( Week 4 ) . During Weeks 2 and 3 , the control group continued to receive generic packages of vegetables presented as a free choice , but the treatment group received vegetables packaged in containers with favorite cartoon characters and stickers inside , presented by parents as the default choice . Children in the treatment group were allowed to opt out of the vegetables and request the granola bar after an imposed 5-minute wait . STATISTICAL ANALYSIS General Linear Model repeated measures analysis of variance was conducted to compare vegetable and granola bar intake between control and treatment groups across the 4-week study . Both within- and between-subjects models were tested . RESULTS A time × treatment interaction on vegetable intake was significant . The treatment group increased vegetable intake from baseline to Week 2 relative to control ( P<0.01 ) , but the effects were not sustained at Week 4 when the treatment was removed . Granola bar intake decreased in the treatment group at Week 2 ( P≤0.001 ) and Week 3 ( P≤0.005 ) relative to baseline . CONCLUSIONS Parents were able to administer feeding practice s derived from behavioral economics and psychology in the home to increase children 's vegetable intake and decrease intake of a high-energy-density snack . Additional studies are needed to test the long-term sustainability of these practice OBJECTIVE To examine whether parents offering a sticker reward to their child to taste a vegetable the child does not currently consume is associated with improvements in children 's liking and consumption of the vegetable . DESIGN A r and omized controlled trial evaluated the effectiveness of exposure only ( EO ) and exposure plus reward ( E + R ) , relative to a control group , on children 's liking and consumption of a target vegetable . Assessment s were conducted at baseline and 2 weeks from baseline ( post-intervention ) . Follow-up assessment s were conducted at 4 weeks and 3 months from baseline . SETTING The study took place in Adelaide , South Australia . Participants were self-selected in response to local media advertisements seeking to recruit parents finding it difficult to get their children to eat vegetables . SUBJECTS Participants were 185 children ( 110 boys , seventy-five girls ) aged 4 - 6 years and their primary caregiver/parent ( 172 mothers , thirteen fathers ) . RESULTS The E + R group was able to achieve more days of taste exposure . Both EO and E + R increased liking at post-intervention compared with control and no further change occurred over the follow-up period . All groups increased their intake of the target vegetable at post-intervention . Target vegetable consumption continued to increase significantly over the follow-up period for E + R and control but not for EO . CONCLUSIONS The findings provide support for the effectiveness of using a sticker reward with a repeated exposure strategy . In particular , such rewards can facilitate the actual tastings necessary to change liking Children 's vegetable intake is below the recommended amounts . No studies to date have tested the relevance of using salt or spices to increase children 's vegetable acceptance . Our objective was to compare the effect of repeated exposure ( RE ) and of flavor-flavor learning ( FFL ) on toddlers ' acceptance of a non-familiar vegetable . Two unconditioned stimuli were used : salt and a salt-associated spice . Toddlers attending six nurseries were assigned to 3 groups in a between subject design . Groups were exposed 8 times to a basic salsify puree ( 0.2 % salt w/w ; RE group ; n = 47 ) , a salty salsify puree ( 0.5 % salt w/w ; FFL-Salt group ; n = 54 ) or a spiced salsify puree ( 0.2 % salt and 0.02 % nutmeg w/w ; FFL-Nutmeg group ; n = 50 ) . Acceptance ( intake and liking ) of the target vegetable ( basic salsify puree ) and of a control vegetable ( carrot puree ) was evaluated at pre-exposure , at each exposure of the learning period , at post-exposure , and at 1 , 3 and 6 months after exposure . In all groups , intake of the target vegetable increased from pre- to post-exposure . This increase was significantly higher in the RE group ( 64 ± 11 g ) than in the FFL-Salt group ( 23 ± 11 g ) and marginally higher than in the FFL-Nutmeg group ( 36 ± 11 g ) . No difference between groups was observed on the increase in liking of the target vegetable from pre- to post-exposure . The increase of the target vegetable intake was still observed after 6 months for all groups . Thus , repeated exposure appears to be the simplest choice to increase vegetable intake on the short and long term in toddlers BACKGROUND Previous portion size research in children has focused on the impact of large entrée portions on children 's intake , but less attention has been given to how intake at a meal is affected across a broader range of entrée portions . OBJECTIVE The objective was to assess the effect of serving a range of entrée portions on children 's ad libitum intake and energy density consumed at the meal . DESIGN A within-subject design was used to examine the effect of varying entrée portions ( ie , 100 , 160 , 220 , 280 , 340 , and 400 g ) on children 's ad libitum energy intake of macaroni and cheese and fixed portions of unsweetened applesauce , green beans , and whole-wheat roll served with the entree . Seventeen children ( 10 girls ) , aged 3 to 6 y , were served a series of 6 lunches , which varied only in entrée portion size , once per week . Weight , height , and weighed food intake were measured . RESULTS Increasing portion size increased children 's entrée intake ( P < 0.01 ) and decreased intake of other foods served with the entrée , including fruit and vegetables ( P < 0.0001 ) . As a result , children consumed a more-energy-dense ( kcal/g ) lunch as portion size increased ( P < 0.0001 ) . Further examination showed that BMI percentile moderated the positive association between portion size and entrée intake ( P < 0.01 ) ; overweight children showed greater increases in entree intake with increasing entrée portion . CONCLUSION Serving smaller age-appropriate entrée portions may be one strategy to improve children 's nutritional profile by decreasing intake of energy-dense foods and by promoting intake of fruit and vegetables served with the entree Previous research suggests that the use of modelling and non-food rewards may be effective at increasing tasting , and consequential liking and acceptance , of a previously disliked food . Although successful school-based interventions have been developed , there is a lack of research into home-based interventions using these methods . This study aim ed to develop and investigate the efficacy of a parent led home-based intervention for increasing children 's acceptance of a disliked vegetable . A total of 115 children aged 2 - 4 years were allocated to one of four intervention groups or to a no-treatment control . The four intervention conditions were : repeated exposure ; modelling and repeated exposure ; rewards and repeated exposure ; or modelling , rewards and repeated exposure . Children in all of the intervention conditions were exposed by a parent to daily offerings of a disliked vegetable for 14 days . Liking and consumption of the vegetable were measured pre and post-intervention . Significant increases in post-intervention consumption were seen in the modelling , rewards and repeated exposure condition and the rewards and repeated exposure condition , compared to the control group . Significant post-intervention differences in liking were also found between the experimental groups . Liking was highest ( > 60 % ) in the modelling , rewards and repeated exposure group and the rewards and repeated exposure group , intermediate ( > 26 % ) in the modelling and repeated exposure and repeated exposure groups , and lowest in the control group ( 10 % ) . Parent led interventions based around modelling and offering incentives may present cost efficient ways to increase children 's vegetable consumption OBJECTIVE This study evaluated whether a nutrition-education program in child-care centers improved children 's at-home daily consumption of fruits and vegetables , at-home use of low-fat/fat-free milk , and other at-home dietary behaviors . MATERIAL S AND METHODS Twenty-four child-care centers serving low-income families were matched by region , type , and size , and then r and omly assigned to either an intervention or control condition . In the 12 intervention centers , registered dietitian nutritionists provided nutrition education to children and parents separately during a 6- to 10-week period . They also held two training sessions for center staff , to educate them on healthy eating and physical activity policies at the centers , and distributed weekly parent newsletters that included activities and recipes . Parents ( n=1,143 ) completed a mail or telephone survey at baseline and follow-up to report information on their child 's fruit , vegetable , and milk consumption and other dietary behaviors at home . This study used general and generalized linear mixed models to evaluate program impacts , while accounting for the clustering of children within centers . This study included child age , child sex , household size , respondent race/ethnicity , respondent age , and respondent sex as covariates . RESULTS The program had a substantial impact on children 's at-home daily consumption of vegetables and use of low-fat/fat-free milk . This study also found a significant increase in the frequency of child-initiated vegetable snacking , which might have contributed to the significant increase in vegetable consumption . The program did not have a significant impact on fruit consumption or parental offerings of fruits and vegetables , child-initiated fruit snacking , or child fruit consumption . CONCLUSIONS This intervention in child-care setting s that emphasized children , parents , and teachers significantly increased at-home vegetable and low-fat/fat-free milk consumption among low-income preschoolers Children 's vegetable consumption is still far below that recommended , and stimulating their intake is a challenge for caregivers . The objective of this study was to investigate whether choice-offering is an effective strategy to increase children 's vegetable intake in an in-home situation . Seventy children ( mean age 3.7 ; SD 1 ) r and omly assigned to a choice or a no-choice condition , were exposed 12 times to six familiar target vegetables at home during dinner . In the choice group , two selected vegetables were offered each time , whereas the no-choice group only received one vegetable . Vegetable intake was measured by weighing children 's plates before and after dinner . A mixed linear model with age , gender , and baseline vegetable liking as covariates was used to compare intake between the choice and the no-choice group . Mixed linear model analysis yielded estimated means for vegetable intake of 48.5 g + /- 30 in the no-choice group and 57.7 g + /- 31 for the choice group ( P = 0.09 ) . In addition , baseline vegetable liking ( P < 0.001 ) and age ( P = 0.06 ) predicted vegetable intake to be higher when the child liked vegetables better and with older age . These findings suggest that choice-offering has some , but hardly robust , effect on increasing vegetable intake in children . Other factors such as age and liking of vegetables also mediate the effect of offering a choice |
2,307 | 19,487,706 | Contribution This r and omized trial found that when a computer-generated report detailing patients ' responses to questions about intimate partner violence and control was attached to medical charts , family practitioners asked about it and detected it more often .
Implication Computer-assisted screening for intimate partner violence and control led to improved detection in a busy ambulatory care setting .
Computer screening may help to overcome some of the barriers to discussing risk for IPV . | Context Domestic violence is difficult to recognize , and screening is often difficult to implement .
The Editors Intimate partner violence ( IPV ) is physical or sexual violence or threats of violence made by one partner to another , often accompanied by controlling behaviors ( 1 ) .
Intimate partner violence is a prevalent and serious health risk for women ( 14 ) .
Several qualitative studies of abused women report that IPV risk assessment by concerned health care providers reduces their feelings of isolation and improves their sense of self-worth , knowledge about re sources , and willingness to seek help ( 3739 ) .
Longitudinal studies show that use of tailored counseling services reduces partners ' controlling behavior or physical violence and , in pregnant women , postnatal depression ( 40 , 41 ) .
In addition , access to employment and social support reduces revictimization ( 42 ) .
Primary care physicians can be pivotal in detecting IPV and offering support and referrals in a timely manner to at-risk women who might otherwise remain silent and delay seeking help ( 43 , 44 ) .
Assessment of the partner 's controlling behavior is important because such acts precede physical violence ( 45 ) or have negative consequences ( 46 ) .
We tested the effectiveness of computer-assisted screening for identifying patients at risk for intimate partner violence or control ( IPVC ) in a Canadian family practice clinic .
We hypothesized that computer-assisted screening of female patients would create opportunities for women to discuss IPVC with their providers and would increase the frequency of IPVC detection compared with st and ard medical care . | STUDY OBJECTIVE We evaluate a computer-based intervention for screening and health promotion in the emergency department and determine its effect on patient recall of health advice . METHODS This controlled clinical trial , with alternating assignment of patients to a computer intervention ( prevention group ) or usual care , was conducted in a university hospital ED . The study group consisted of 542 adult patients with nonurgent conditions . The study intervention was a self-administered computer survey generating individualized health information . Outcome measures were ( 1 ) patient willingness to take a computerized health risk assessment , ( 2 ) disclosure of behavioral risk factors , ( 3 ) requests for health information , and ( 4 ) remembered health advice . RESULTS Eighty-nine percent ( 470/542 ) of eligible patients participated . Ninety percent were black . Eighty-five percent ( 210/248 ) of patients in the prevention group disclosed 1 or more major behavioral risk factors including current smoking ( 79/248 ; 32 % ) , untreated hypertension ( 28/248 ; 13 % ) , problem drinking ( 46/248 ; 19 % ) , use of street drugs ( 33/248 ; 13 % ) , major depression ( 87/248 ; 35 % ) , unsafe sexual behavior ( 84/248 ; 33 % ) , and several other injury-prone behaviors . Ninety-five percent of patients in the prevention group requested health information . On follow-up at 1 week , 62 % ( 133/216 ) of the prevention group patients compared with 27 % ( 48/180 ) of the control subjects remembered receiving advice on what they could do to improve their health ( relative risk 2.3 , 95 % confidence interval 1.77 to 3.01 ) . CONCLUSION Using a self-administered computer-based health risk assessment , the majority of patients in our urban ED disclosed important health risks and requested information . They were more likely than a control group to remember receiving advice on what they could do to improve their health . Computer methodology may enable physicians to use patient waiting time for health promotion and to target at-risk patients for specific interventions BACKGROUND Women experiencing domestic violence ( DV ) frequent health care setting s , but DV is rarely identified . METHODS We conducted a r and omized controlled trial to determine the effect of computer screening on health care provider-patient DV communication at 2 socioeconomically diverse emergency departments ( EDs ) . Consenting nonemergent female patients , aged 18 to 65 years , were r and omized to self-administered computer-based health risk assessment , with a prompt for the health care provider , or to " usual care " ; all visits were audiotaped . Outcome measures were rates of DV discussion , disclosure , and services . RESULTS Of 2169 eligible patients , 1281 ( 59 % ) consented ; 871 ( 68 % ) were successfully audiotaped , and 903 ( 71 % ) completed an exit question naire . Rates of current DV risk on exit question naire were 26 % in the urban ED and 21 % in the suburban ED . In the urban ED , the computer prompt increased rates of DV discussion ( 147/262 [ 56 % ] vs 123/275 [ 45 % ] ; P = .004 ) , disclosure ( 37/262 [ 14 % ] vs 23/275 [ 8 % ] ; P = .07 ) , and services provided ( 21 [ 8 % ] vs 10 [ 4 % ] ; P = .04 ) . Women at the suburban site and those with private insurance or higher education were much less likely to be asked about experiences with abuse . Only 48 % of encounters with a health care provider prompt regarding potential DV risk led to discussion s. Both inquiries about and disclosures of abuse were associated with higher patient satisfaction with care . CONCLUSIONS Computer screening for DV increased but did not guarantee that DV would be addressed during ED encounters . Nonetheless , it is likely that low-cost interventions that allow patients the opportunity to self-disclose can be used to improve detection of DV Background : A pregnant woman 's psychological health is a significant predictor of postpartum outcomes . The Antenatal Psychosocial Health Assessment ( ALPHA ) form incorporates 15 risk factors associated with poor postpartum outcomes of woman abuse , child abuse , postpartum depression and couple dysfunction . We sought to determine whether health care providers using the ALPHA form detected more antenatal psychosocial concerns among pregnant women than providers practising usual prenatal care . Methods : A r and omized controlled trial was conducted in 4 communities in Ontario . Family physicians , obstetricians and midwives who see at least 10 prenatal patients a year enrolled 5 eligible women each . Providers in the intervention group attended an educational workshop on using the ALPHA form and completed the form with enrolled women . The control group provided usual care . After the women delivered , both groups of providers identified concerns related to the 15 risk factors on the ALPHA form for each patient and rated the level of concern . The primary outcome was the number of psychosocial concerns identified . Results were controlled for clustering . Results : There were 21 ( 44 % ) providers r and omly assigned to the ALPHA group and 27 ( 56 % ) to the control group . A total of 227 patients participated : 98 ( 43 % ) in the ALPHA group and 129 ( 57 % ) in the control group . ALPHA group providers were more likely than control group providers to identify psychosocial concerns ( odds ratio [ OR ] 1.8 , 95 % confidence interval [ CI ] 1.1–3.0 ; p = 0.02 ) and to rate the level of concern as “ high ” ( OR 4.8 , 95 % CI 1.1–20.2 ; p = 0.03 ) . ALPHA group providers were also more likely to detect concerns related to family violence ( OR 4.8 , 95 % CI 1.9–12.3 ; p = 0.001 ) . Interpretation : Using the ALPHA form helped health care providers detect more psychosocial risk factors for poor postpartum outcomes , especially those related to family violence . It is a useful prenatal tool , identifying women who would benefit from additional support and interventions Objective To compare two different screening techniques for identifying women with a history of domestic violence or battering in the current pregnancy . Methods The five- question Abuse Assessment Screen was incorporated into routine social service interviews and applied prospect ively to all registrants for routine prenatal care at Women & Infants ' Hospital during an initial social service evaluation from September 7 through October 29 , 1993 . This group ( N = 143 ) was compared to a historical control group of all new registrants from July 12 through September 3 , 1993 ( N = 191 ) who had routine interviews by social services . Demographic and medical data were compared , as well as the specific information addressed by the screen , including history of domestic violence , physical or sexual violence within the last year , violence during the current pregnancy , recent sexual abuse , and fear of partner . Results The median age of the study population was 23 years old , 50 % were white , 63 % were single , and 42 % had no insurance . There was a higher detection of violence in all categories using the Abuse Assessment Screen compared with the st and ard interview — any history : 41 versus 14 % ( relative risk [ RR ] 3.0 , 95 % confidence interval [ CI ] 2.0–4.5 ) ; recent history : 15 versus 3 % ( RR 5.6 , CI 2.2–14.5 ) ; during pregnancy : 10 versus 1 % ( RR 9.3 , CI 2.2–40.5 ) ; recent sexual abuse : 4 versus 0 % ( P = .006 ) ; and fear of abuser : 6 versus 3 % ( RR 1.8 , CI 0.6–5.0 ) . Conclusion Use of a structured screen improves detection rates of battering both before and during pregnancy , enabling clinicians to have a greater opportunity to intervene Although violence against women is recognized as a major public health problem , few interventions have been developed to reduce abuse . In this study , 132 pregnant women received three counseling sessions that were design ed to reduce further abuse . A comparison group of 67 abused women were offered wallet-sized cards listing community re sources for abuse . Women in both groups were followed at 6 months and 12 months post-delivery . Using repeated measures MANCOVA with entry scores as a covariate , we found significantly less violence reported by women in the intervention group than by women in the comparison group Objective To evaluate the effectiveness of an empowerment intervention in reducing intimate partner violence ( IPV ) and improving health status OBJECTIVE To examine the relationship between intimate partner violence ( IPV ) type , severity , and duration and abused women 's use of medical and legal services . METHODS Participants were 1509 r and omly sample d women from a large health plan who were interviewed by telephone to assess ( 1 ) self-reported lifetime exposure to IPV type ( physical , sexual , and psychological ) , severity , and duration and ( 2 ) women 's use of medical and legal services ( civil protection orders ) . RESULTS Compared with women who experienced psychological abuse only , sexually abused women were 1.3 times as likely to seek medical care , and women exposed to physical IPV or sexual IPV were 3.2 times and 1.6 times as likely , respectively , to seek legal services . Rates of medical and legal help seeking increased with increasing abuse severity among physically abused women , and rates of legal help seeking increased with abuse severity among sexually and psychologically abused women . Longer duration of physical and sexual IPV was also found to be associated with increased legal help seeking . CONCLUSIONS Abused women who sought formal help were more likely to be exposed to physical or sexual IPV , severe psychological IPV , and severe and long-lasting physical and sexual IPV . Efforts should be considered to improve the healthcare and legal system 's response to IPV OBJECTIVE Our goal was to identify the prevalence , determinants of , and barriers to clinician-patient communication about intimate partner abuse . STUDY DESIGN We conducted telephone interviews with a r and om sample of ethnically diverse abused women . POPULATION We included a total of 375 African American , Latina , and non-Latina white women aged 18 to 46 years with histories of intimate partner abuse who attended 1 of 3 primary care clinics in San Francisco , California , in 1997 . OUTCOMES MEASURED We measured the relevance and determinants of past communication with clinicians about abuse and barriers to communication . RESULTS Forty-two percent ( 159 ) of the patients reported having communicated with a clinician about abuse . Significant independent predictors of communication were direct clinician question ing about abuse ( odds ratio [OR]=4.6 ; 95 % confidence interval [ CI ] 3.2 - 6.6 ) , and African American ethnicity ( OR=1.8 ; 95 % CI , 1.1 - 2.9 ) . Factors associated with lack of communication about abuse included immigrant status ( OR=0.6 ; 95 % CI , 0.3 - 1.0 ) and patient concerns about confidentiality ( OR=0.7 ; 95 % CI , 0.5 - 0.9 ) . Barriers significantly associated with lack of communication were patients ' perceptions that clinicians did not ask directly about abuse , beliefs that clinicians lack time and interest in discussing abuse , fears about involving police and courts , and concerns about confidentiality . CONCLUSIONS Clinician inquiry appears to be one of the strongest determinants of communication with patients about partner abuse . Other factors that need to be addressed include patient perceptions regarding clinicians ' time and interest in discussing abuse , fear of police or court involvement , and patient concerns about confidentiality OBJECTIVES National health care organizations recommend routinely screening patients for behavioral health risks , the effectiveness of which depends on patients ' willingness to disclose risky behaviors . This study aim ed to determine if primary care patients ' disclosures of potentially stigmatizing behaviors would be affected by ( 1 ) their expectation about whether or not their physician would see their disclosures and ( 2 ) the assessment method . METHODS One thous and nine hundred fifty-two primary care patients completed a question naire assessing human immunodeficiency virus ( HIV ) , alcohol , drug , domestic violence , tobacco , oral health , and seat belt risks ; half were told their responses would be seen by the research er and their physician and half were told that their responses would be seen by the research er only . Patients were r and omly assigned to one of five assessment methods : written , face-to-face , audio-based , computer-based , or video-based . RESULTS Across all risk areas , patients did not disclose differently whether or not they believed their physician would see their disclosures . Technologically advanced assessment methods ( audio , computer , and video ) produced greater risk disclosure ( 4%-8 % greater ) than traditional methods in three of seven risk areas . CONCLUSIONS These findings suggest patients are not less willing to disclose health risks to a research assistant knowing that this information would be shared with their physician and that a number of assessment methods can effectively elicit patient disclosure . Potentially small increases in risk disclosure must be weighed against other factors , such as cost and convenience , in determining which method ( s ) to use in different health care setting CONTEXT Screening for intimate partner violence ( IPV ) in health care setting s has been recommended by some professional organizations , although there is limited information regarding the accuracy , acceptability , and completeness of different screening methods and instruments . OBJECTIVE To determine the optimal method for IPV screening in health care setting s. DESIGN AND SETTING Cluster r and omized trial conducted from May 2004 to January 2005 at 2 each of emergency departments , family practice s , and women 's health clinics in Ontario , Canada . PARTICIPANTS English-speaking women aged 18 to 64 years who were well enough to participate and could be seen individually were eligible . Of 2602 eligible women , 141 ( 5 % ) refused participation . INTERVENTION Participants were r and omized by clinic day or shift to 1 of 3 screening approaches : a face-to-face interview with a health care provider ( physician or nurse ) , written self-completed question naire , and computer-based self-completed question naire . Two screening instruments-the Partner Violence Screen ( PVS ) and the Woman Abuse Screening Tool (WAST)-were administered and compared with the Composite Abuse Scale ( CAS ) as the criterion st and ard . MAIN OUTCOME MEASURES The approaches were evaluated on prevalence , extent of missing data , and participant preference . Agreement between the screening instruments and the CAS was examined . RESULTS The 12-month prevalence of IPV ranged from 4.1 % to 17.7 % , depending on screening method , instrument , and health care setting . Although no statistically significant main effects on prevalence were found for method or screening instrument , a significant interaction between method and instrument was found : prevalence was lower on the written WAST vs other combinations . The face-to-face approach was least preferred by participants . The WAST and the written format yielded significantly less missing data than the PVS and other methods . The PVS and WAST had similar sensitivities ( 49.2 % and 47.0 % , respectively ) and specificities ( 93.7 % and 95.6 % , respectively ) . CONCLUSIONS In screening for IPV , women preferred self-completed approaches over face-to-face question ing ; computer-based screening did not increase prevalence ; and written screens had fewest missing data . These are important considerations for both clinical and research efforts in IPV screening . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00336297 This study examined interpersonal and ecological predictors of re-victimization of a sample of women with abusive partners . All women ( N = 124 ) had sought refuge from a battered women ’s shelter 3 years earlier , and half the sample had been r and omly assigned to receive free , short-term advocacy services immediately upon exit from the shelter . Results 2 years post-intervention revealed positive change in the lives of participants ( C. M. Sullivan & D. Bybee , 1999 ) , including a decrease in abuse for women who had worked with advocates . The current study examined intervention effects 3 years after the program ended , as well as other predictors of re-abuse . Nineteen percent of the original sample had experienced domestic violence between 2 and 3 years after shelter exit ( 65 % by current partners , 35 % by ex-partners ) . The advocacy program ’s effect on risk of re-victimization did not continue 3 years post-intervention . However , having worked with an advocate 3 years prior continued to have a positive impact on women ’s quality of life and level of social support . The risk of being abused 3 years post-shelter stay was exacerbated by a number of factors present 1 year prior , including women ’s ( 1 ) having experienced abuse in the 6 months before that point ; ( 2 ) having difficulties accessing re sources ; ( 3 ) having problems with the state welfare system ; and ( 4 ) having people in their social networks who made their lives difficult . Women were at less risk of abuse if , 1 year earlier , they ( 1 ) were employed ; ( 2 ) reported higher quality of life ; and ( 3 ) had people in their networks who provided practical help and /or were available to talk about personal matters . These findings support the hypothesis that access to re sources and social support serve as protective factors against continued abuse Context Victims of domestic violence often seek care in emergency departments . Contribution This study examines 293 audiotaped visits to 2 emergency departments during which providers screened adult women for domestic violence . Providers ' queries were often perfunctory . They usually did not include follow-up probing or offer open-ended opportunities to talk . Seventy-seven women disclosed domestic violence during the interviews ; however , providers documented only 24 of the disclosures and referred only 19 women for counseling . Caution Audiotapes were made during a r and omized trial that was testing computer screening for domestic violence . Providers knew they were being audiotaped . Implication Poor communication with victims of domestic violence is probably very common in emergency departments . The Editors Communication about domestic violence has been studied retrospectively through reports of victims and health care providers . Victims frequently report difficulties in disclosing their experiences with domestic violence to health care providers ( 16 ) . However , with the exception of participant observation work by Kurz in the 1980s ( 7 ) , research is lacking on what actually transpires when physicians and patients talk about domestic violence . Direct observation can provide useful examples of successful screening and guide educational programs for providers . We performed a qualitative analysis of audiotaped domestic violence conversations that occurred between female patients and their emergency providers . The parent study , a r and omized , controlled trial of a computer screening intervention , found a significant increase in the frequency of domestic violence discussion s associated with the intervention ( 8) . The computer-based health risk assessment included questions about abuse and a prompt to the provider to ask about possible risk . We describe here the actual communication between providers and patients and identify common pitfalls and exemplary practice s. Methods From June 2001 to December 2002 , we conducted a r and omized , controlled trial of a self-administered computer-based health risk assessment tool , which generated health recommendations for patients and alerted physicians to a variety of potential health risks , including domestic violence . The trial took place at 2 socioeconomically diverse emergency departments : an urban academic medical center that serves a predominately publicly insured , inner-city , African-American population , and a suburban community hospital that serves a predominately privately insured , white population . Inclusion criteria were sequential female patients 18 to 65 years of age who were triaged as medically nonemergent and could give consent . The emergency providers ( 40 attending physicians , 46 residents , and 4 nurse practitioners ) involved in the study were aware that the intent was to increase detection of domestic violence . Before the start of data collection , providers received a 1-hour lecture and a 30-minute video and instruction guide about assessing safety and documenting and providing referrals related to domestic violence ( 9 ) . Figure 1 shows the study flow . Successfully audiotaped emergency visits ( n= 871 ) were deidentified , and all audible domestic violence discussion s ( n= 293 ) between providers and patients were excerpted for transcription and coding . Patients and providers signed written consent , and the institutional review boards of both institutions approved the study . The study ended at patient discharge ; there was no subsequent patient follow-up , but all participating patients received information on domestic violence services in the form of a magnet listing a variety of community re sources . Figure 1 . Study flow diagram . ED= emergency department . Audiocoding A structured domestic violence coding scheme was developed in an iterative manner through group listening and discussion among the authors ( 10 ) , who have expertise in physicianpatient communication , emergency medicine , and domestic violence and psychology . The coding scheme was loosely based on a theoretical framework that patients often hint at their concerns and present their providers with potential empathic opportunities when they discuss psychosocial issues ( 1113 ) . The coding scheme was design ed to identify the range , scope , and frequencies of common practice s , as well as key examples of best and worst practice s. Best practice s were assessed on the basis of literature about what domestic violence survivors find to be helpful ( 9 , 14 , 15 ) and the existing medical communication literature about sensitive issues ( 16 ) . A domestic violence discussion was defined as any mention of physical or emotional abuse during the encounter . Domestic violence disclosure was defined as any patient mention of current or past abuse in an intimate or family relationship . All domestic violence discussion s were coded independently by at least 2 authors , who used the final structured coding form while listening to the audiotape and reading the transcript . This was further refined after independent coding of a 15 % r and om sample until agreement for key domestic violence variables was nearly perfect . All coding was examined for discrepancies , which were further review ed through group listening and discussed until consensus was achieved . Role of the Funding Source The study was funded by the Agency for Healthcare Research and Policy , which had no involvement in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . All authors had full access to the data files for this study . Results We obtained 293 audiotapes that included a discussion of domestic violence . Patients were predominantly African American ( 83 % ) and single ( 63 % ) , and 18 % had less than a high school education . Only 77 of the 293 domestic violence discussion s included patient disclosure of domestic violence to the provider . Table 1 compares the demographic characteristics of enrolled patients with and without useable audiotapes and shows that audiotaped patients who did or did not disclose abuse to the provider were similar . Table 2 shows demographic characteristics of providers . Patients were usually seen by more than 1 provider , which is typical at teaching hospitals . Table 1 . Characteristics of Enrolled Patients Table 2 . Characteristics of Participating Providers Patient disclosure of abuse usually referred to an intimate partner , although 9 patients ( 12 % ) reported intrafamilial , acquaintance , or other types of domestic violence . Although most of the providers did not directly question patients about when the violence occurred , 27 ( 35 % ) patients indicated that the abuse was a current issue in their lives and 34 ( 44 % ) disclosed past experiences with abuse . Two patients reported both past and present abuse . In conversations in which the type of abuse was discernible , 12 ( 16 % ) patients disclosed emotional abuse and 26 ( 34 % ) disclosed physical abuse . Five patients ( 6 % ) mentioned both emotional and physical abuse . Only 24 of the 77 patients ( 32 % ) who disclosed abuse to the provider had any documentation of this discussion in their chart . Context and Characteristics of Provider Inquiry Table 3 shows the context of the domestic violence discussion s , which were almost always initiated by providers during the social history , as part of a checklist of risk factors . For example , a provider might ask , Do you smoke ? Do you drink alcohol often or use any street drugs ? Do you have any problems with domestic violence ? Table 3 . Context of Domestic Violence Discussion Table 4 shows examples of communication strategies that emergency department providers used to discuss domestic violence . Most often , provider inquiry was a variation of the question , Are you a victim of domestic violence ? Screening questions were frequently ( 45 % ) asked in a perfunctory manner and were sometimes ( 10 % ) framed in the negative : He 's never hit you ? Approximately one third of the time , providers probed ( defined as asking 1 follow-up question after a patient 's initial response ) for further information ; 10 % of the time , this included in-depth question ing or a detailed domestic violence history . Providers mentioned the computer screening 15 % of the time . Table 4 . Examples of Provider Communication Strategies Communication Strategies and Disclosure of Abuse Table 5 shows provider communication strategies that appeared to be associated with patient disclosure . Patient disclosure of abuse was more likely to be found in audiotapes in which the provider probed for domestic violence , created open-ended opportunities for discussion , and was generally responsive or expressed empathy when a patient mentioned a psychosocial issue ( for example , stress ) . However , disclosures still occurred when the provider hesitated ; used broken syntax , such as um ; or laughed during the course of the domestic violence conversation . In the following excerpt , the provider elicited a traumatic abuse history from a young woman who presented with irregular menses just by mentioning the word stress and following up on a clue about a recent change : Table 5 . Provider Inquiry Characteristics , by Patient Domestic Violence Disclosure Status Provider : You can have irregular periods and just get plumbing problems . You can just be under a lot of stress . Patient : That 's what I 'm worried about . Cause I have nt had one since May. Provider : Has it been worse at home since May ? Patient : ( 1-second pause ) Yeah , it has . I had to leave home because my fatherhe was real terrible He came in the room and he took the phone from me and then he threw it . So , at that , uh , point , I was just scared . My momma , sheshe was shaking . And he also had aa knife in his h and . he was trying to stab me . Common Pitfalls The opportunity to have a meaningful conversation about abuse was often diminished by provider factors , such as screening the patient in the presence of a third party , failure to acknowledge disclosure of abuse , OBJECTIVE To assess the occurrence , frequency , and severity of physical abuse during pregnancy and associated initiation of prenatal care . DESIGN Stratified , prospect i ve cohort analysis . SETTING Public prenatal clinics in Houston , Tex , and Baltimore , Md. PARTICIPANTS Total population -based sample of 691 black , Hispanic , and white pregnant women . All of the women were urban residents and most of the Hispanic women were Mexican American . All participants were invited into the study at the first prenatal visit and were followed up until delivery . MAIN OUTCOME MEASURE Identification of abuse status . RESULTS A three- question Abuse Assessment Screen detected a 17 % ( 1/6 ) prevalence of physical or sexual abuse during pregnancy , which is more than double all previous published reports . When evaluated against nationally tested research instruments , the three- question screen that was asked at the first prenatal visit was sensitive and specific to abuse status . Abuse was recurrent , with 60 % of abused women reporting two or more episodes of assault . Location of abuse focused on the head . Frequency and severity of abuse and potential danger of homicide was appreciably worse for white women . Abused women were twice as likely as nonabused women to begin prenatal care during the third trimester . CONCLUSIONS A simple clinical assessment screen completed by the health care provider in a private setting and with the male partner absent is as effective as research instruments in identifying abused women . Straightforward , routine clinical assessment is recommended as essential in preventing potential trauma , interrupting existing abuse , and protecting health Although an estimate of the odds ratio adjusted for other covariates can be obtained by logistic regression , until now there has been no simple way to estimate other interesting parameters such as the risk ratio and risk difference multivariately for prospect i ve binomial data . These parameters can be estimated in the generalized linear model framework by choosing different link functions or transformations of binomial or binary data . Macros for use with the program GLIM provide a simple method to compute parameters other than the odds ratio while adjusting for confounding factors . A data set presented previously is used as an example |
2,308 | 17,636,653 | There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene-resistant PCOS undergoing LOD compared to gonadotrophin treatment .
The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive . | BACKGROUND Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome ( PCOS ) but was largely ab and oned due to the risk of postsurgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins .
However , women with PCOS who are treated with gonadotrophins often have an over-production of follicles which may result in ovarian hyperstimulation syndrome ( OHSS ) and multiple pregnancies .
Moreover , gonadotrophins , though effective , are costly and time-consuming requiring intensive monitoring .
Surgical therapy with laparoscopic ovarian ' drilling ' ( LOD ) may avoid or reduce the need for gonadotrophins or may facilitate their usefulness .
The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches .
Many uncontrolled observational studies have cl aim ed that ovarian drilling is followed , at least temporarily , by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier .
OBJECTIVES To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS . | AIM To evaluate the effects of metformin on insulin resistance , and rogen concentration , ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome ( PCOS ) . METHODS Forty-two infertile women with PCOS were selected in this r and omized clinical study . Basal steroid and gonadotropin levels were measured , and oral glucose tolerance test ( OGTT ) was performed . The patients were r and omly divided into group 1 ( n = 21 ) and group 2 ( n = 21 ) . Group 1 patients were treated with laparoscopic ovarian drilling ( LOD ) . Group 2 patients underwent laparoscopic ovarian drilling ( LOD ) and received 1700 mg per day of metformin for 6 months . LOD was performed in women with PCOS using a unipolar electrode . Serum progesterone ( P ) level > 5 ng/mL was considered as a confirmation of ovulation . Ovulation and pregnancy rates were determined after six cycles . RESULTS Serum and rogens and insulin response to OGTT decreased significantly after metformin therapy . Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD ( 34.6 + /- 25.4 ng/mL , 8.4 + /- 1.1 mm ) than in those treated with LOD alone ( 26.2 + /- 24.7 ng/mL , 7.9 + /- 2.8 mm ) ( P < 0.05 ) . The ovulation ( 56 of 65 cycles , 86.1 % vs 29 of 65 cycles , 44.6 % ) and pregnancy rates ( nine of 21 women , 47.6 % vs four of 21 women , 19.1 % ) were significantly higher in group 2 than in group I. CONCLUSIONS Metformin improves insulin resistance , reduces and rogen levels and significantly increases the ovulation and pregnancy rates in infertile women , following LOD Laparoscopic Nd-YAG laser photocoagulation of the ovaries was performed in 40 anovulatory women with clomiphene citrate-resistant polycystic ovary disease . Following this procedure , the subjects were r and omly assigned to have either a second-look laparoscopy with lysis of adhesions within 3 - 4 weeks of the initial laparoscopy ( N=19 ) or expectant management ( N=20 ) . One patient assigned to the laparoscopy group refused the procedure . Minimal and mild adhesions that did not distort the normal tubo-ovarian relationship were encountered in 13 patients ( 68 % ) in the second-look laparoscopy group ; these adhesions were easily lysed using sharp or blunt dissection . The pregnancy rates over 6 months were similar in the two groups ( 47 % in the second-look group and 55 % in the expectant-management group ; P>.05 ) . These data suggest that early laparoscopic lysis of adhesions does not improve short-term conception rates following laparoscopic Nd-YAG laser photocoagulation of polycystic ovaries Objectives Laparoscopic ovarian drilling ( LOD ) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) , with tubo-ovarian adhesion formation as the major disadvantage . Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling . Methods This prospect i ve r and omized study included 44 patients with anovulatory infertility due to PCOS . Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007 . The number of drilling site in each ovary was limited to five . The clinical and biochemical response , ovulation and pregnancy rates over a follow-up period of 1 year were compared . Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy . Results There was no statistical difference between the two groups in terms of clinical and biochemical response , ovulation rate and pregnancy rate . Postoperatively , tubo-ovarian adhesions could be assessed in 36.3 % of the patients and no adhesions were found in a single case in either group . Conclusion Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy . Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation Objective : We compared 12-month pregnancy and live birth rates in patients with polycystic ovarian disease undergoing 5- , 10- , and 15-point laparoscopic ovarian electrocauterization . Methods : This was a prospect i ve , r and omized study performed at the Dabirashrafi Fertility and Endoscopy Research Center , Tehran , Iran . The study included 187 patients with polycystic ovarian disease who were r and omly assigned to 3 groups . Group I comprised 67 patients whose ovaries received 5-point electrocauterization . Group II comprised 57 patients whose ovaries received 10-point electrocauterization . Group III comprised 63 patients whose ovaries received 15-point electocauterization . Laparoscopic ovarian electrocauterization with a unipolar current was used . The main outcome measures were 12-month pregnancy and live birth rates . Results : Patients were homogeneous for age , body mass index , and type and duration of infertility . Twenty pregnancies result ed in Group I , with a pregnancy rate of 29.9 % ( 20/67 ) and a live birth rate of 20.9 % ( 14/57 ) . Eighteen pregnancies result ed in Group II , with a pregnancy rate of 31.6 % ( 18/57 ) , and a live birth rate of 28.1 % (16/57).Thirty-three pregnancies result ed in group III , with a pregnancy rate of 52.4 % ( 33/63 ) , and a live birth rate of 47.6 % ( 30/63 ) . Comparison of Group III with Groups I and II revealed a statistically significant increase in pregnancies ( P=0.016 ) and live birth rates ( P=0.004 ) . Conclusion : We recommend 15-point electrocauterization of ovaries in patients with polycystic ovarian disease In this prospect i ve , r and omized , controlled clinical study , 21 women underwent a second-look laparoscopy 2 - 11 weeks after st and ardized laparoscopic electrosurgical treatment for polycystic ovarian syndrome ( PCOS ) . Following bilateral ovarian treatment , one ovary was r and omly chosen to have Interceed applied to its surface using a specially design ed applicator , with the other ovary serving as a control . Peri-adnexal adhesions of significant extent and severity developed in 57 % of the women and 38 % of the adnexa . The incidence of adhesions on the Interceed-treated side was 43 % , while on the control side it was 33 % . In addition , the extent and severity of the adhesions appeared to be similar on the Interceed-treated and control side . However , larger numbers would be required to determine statistically the effects of Interceed on de-novo adhesion formation after laparoscopic electrosurgical treatment of PCOS , as described here Objectives Rosiglitazone , an insulin sensitizing agent is used currently in women with clomiphene citrate ( CC ) resistant polycystic ovarian syndrome ( PCOS ) . Our study proposed to compare the efficacy of rosiglitazone and CC with laparoscopic ovarian drilling ( LOD ) and CC in terms of biochemical effects , ovulation rate and pregnancy rate in patients of PCOS resistant to CC . Methods This prospect i ve r and omised trial included 43 patients of PCOS resistant to CC . Twenty-two women were assigned to the rosiglitazone ( 4 mg twice daily ) and CC group and other 21 patients underwent unilateral LOD and then received CC and multivitamins . The treatment continued for six cycles in both the groups . The biochemical response , ovulation rate and pregnancy rate over a follow up period of 6 months were compared . Results Treatment with rosiglitazone and CC or LOD and CC result ed in increased ovulation ( 80.8 vs. 81.5 % ) and pregnancy ( 50 vs. 42.8 % ) , respectively . There was no statistical difference between the two groups in terms of biochemical response , ovulation rate and pregnancy rate . Conclusion To avoid the risk of adverse effects of LOD preference may be given to the use of rosiglitazone and CC therapy in patients of PCOS resistant to CC Fifty women with polycystic ovaries took part in a prospect i ve r and omized study . All women required treatment by in-vitro fertilization ( IVF ) for reasons other than anovulation . They had all previously undergone ovarian stimulation with gonadotrophin therapy which had failed to result in pregnancy or had been ab and oned due to high risk of developing ovarian hyperstimulation syndrome ( OHSS ) . Twenty-five women were treated by long-term pituitary desensitization followed by gonadotrophin therapy , oocyte retrieval and embryo transfer ( group 1 ) . Twenty-five women underwent laparoscopic ovarian electrocautery after pituitary desensitization followed by gonadotrophin therapy , oocyte retrieval and embryo transfer ( group 2 ) . A significantly higher number of women in group 1 had to have the treatment cycle ab and oned due to impending or actual OHSS , determined by endocrine and clinical findings . In addition , the development of moderate or severe OHSS in completed cycles was higher in group 1 . The pregnancy rate and miscarriage rates in the two treatment groups were similar . The authors propose that laparoscopic ovarian electrocautery is a potentially useful treatment for women who have previously had an IVF treatment cycle cancelled due to risk of OHSS or who have suffered OHSS in a previous treatment cycle BACKGROUND Laparoscopic ovarian diathermy ( LOD ) is currently accepted as a successful second-line treatment for ovulation induction ( OI ) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome ( PCOS ) . The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment . METHODS The study included 72 anovulatory women with PCOS who were r and omized to LOD ( n = 36 ) or CC ( n = 36 ) . Women who remained anovulatory after LOD were offered CC . Similarly , women receiving CC who failed to ovulate or conceive were offered LOD . Pregnancy rates were compared between the two groups using chi(2 ) and odds ratio with 95 % confidence interval ( OR , 95 % CI ) . RESULTS After r and omization , six women conceived before starting treatment and another patient postponed treatment . The remaining 65 women received the treatment ( 33 underwent LOD and 32 received CC ) . After the primary treatment , more pregnancies ( 44 % ) occurred in women receiving CC than in those undergoing LOD ( 27 % ) , although the difference did not reach statistical significance [ P = 0.13 , OR 2.1 ( 0.7 - 5.8 ) ] . After adding the second treatment , the pregnancy rate was still higher , but to a less extent , in the CC group [ 63 % versus 52 % , P = 0.2 , OR 1.6 ( 0.6 - 4.2 ) ] . CONCLUSIONS LOD is not superior to CC as a first-line method of OI in women with PCOS . The trial is registered with Clinical Trials.gov with an identifier number NCT00220545 The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial . The present prospect i ve longitudinal follow-up study was design ed to identify whether certain criteria assessed during st and ardized initial screening could predict the response to ovulation induction with clomiphene citrate ( CC ) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility . Serum FSH levels were within the normal range ( 1 - 10 IU/L ) , and all patients underwent spontaneous or progestin-induced withdrawal bleeding . Initial CC doses were 50 mg daily for 5 days starting on cycle day 3 . In the case of an absent response , doses were increased to 100 and 150 mg daily in subsequent cycles . First ovulation with CC was used as the end point . After a complete follow-up ( in the case of a nonresponse , at least 3 treatment cycles with daily CC doses up to 150 mg ) , 156 patients ( 78 % ) ovulated . The free and rogen index ( FAI = testosterone/sex hormone-binding globulin ratio ) , body mass index ( BMI ) , cycle history ( oligomenorrhea vs. amenorrhea ) , serum and rogen ( testosterone and /or and rostenedione ) levels , and mean ovarian volume assessed by transvaginal sonography were all significantly different ( P < 0.01 ) in responders from those in nonresponders . FAI was chosen to be the best predictor in univariate analysis . The area under the receiver operating characteristics curve in a multivariate prediction model including FAI , BMI , cycle history , and mean ovarian volume was 0.82 . Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics , such as FAI , BMI , cycle history ( oligomenorrhea or amenorrhea ) , and mean ovarian volume . These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women Laparoscopic ovarian drilling ( LOD ) is the accepted second-line treatment for clomiphene citrate-resistant anovulatory infertility in polycystic ovary syndrome ( PCOS ) . Although multiple pregnancy rates are reduced with ovarian drilling procedures , postoperative adhesion formation is a potential complication in up to 85 % of the women subjected to laparoscopic destructive ovarian procedures . Our objective was to determine the effectiveness of a new , specially design ed laparoscopic device and technique that might enable treatment for patients with anovulatory PCOS with less trauma and fewer postoperative adhesions . Thirty-five infertile clomiphene citrate-resistant women with PCOS were included . Seventeen women underwent laparoscopic ovarian multi-needle intervention ( LOMNI ) , and 18 women received step-up ovulation induction treatment with recombinant follicle-stimulating hormone followed by intrauterine insemination for three cycles . Patients were followed for a period of 6 months after either laparoscopic surgery or the initiation of ovulation induction therapy . Outcome measures were cycle regularity , pregnancy rate , safety , postoperative adhesion formation , and cost effectiveness . There were no significant differences between the two groups in terms of age , body-mass index , duration of infertility , and basal cycle-day 2 hormone levels . Significant improvement in cycle regularity ( p < .01 ) was found after LOMNI . Cumulative pregnancy rates ( 35.3 % in the LOMNI group vs 33.3 % in the ovulation induction group ) did not differ between the groups . No adverse events following surgery were noted . Moderate ovarian hyperstimulation syndrome and multiple pregnancies occurred in four and two patients , respectively , in the ovulation induction group . Eight nonpregnant women in the LOMNI group underwent repeat laparoscopy at the end of the follow-up period . No adhesion formation attributable to LOMNI was observed in any of those eight women . The cost of LOMNI was significantly ( p < .001 ) lower than the ovulation induction treatment . In conclusion , LOMNI may be a safe , inexpensive , and effective procedure for the treatment of CC-resistant infertility in patients with PCOS . It seems to preserve the beneficial effects and probably omits unwanted effects ( such as adhesion formation ) of LOD |
2,309 | 11,869,581 | There was strong evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved function when compared with inpatient or outpatient non-multidisciplinary treatments .
There was moderate evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved pain when compared with outpatient non-multidisciplinary rehabilitation or usual care .
There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary bio-psycho-social intervention .
Some trials reported improvements in work readiness , but others showed no significant reduction in sickness leaves .
Less intensive outpatient psycho-physical treatments did not improve pain , function or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care .
Few trials reported effects on quality of life or global assessment s. REVIEW ER 'S CONCLUSIONS The review ed trials provide evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improves pain and function .
Less intensive interventions did not show improvements in clinical ly relevant outcomes | BACKGROUND Chronic low back pain is , in many countries , the main cause of long term disability in middle age .
Patients with chronic low back pain are often referred for multidisciplinary treatment .
Previous published systematic review s on this topic included no r and omised controlled trials and pooled together controlled and non-controlled studies .
OBJECTIVES To assess the effect of multidisciplinary bio-psycho-social rehabilitation on pain , function , employment , quality of life and global assessment outcomes in subjects with chronic disabling low back pain . | One hundred sixteen consecutive patients entered a functional restoration treatment program for chronic low back pain and were compared with 72 patients not treated . A two-year follow-up survey reached more than 85 % of both groups ; its findings were compared with earlier results of a five-month and one-year follow-up . Analysis demonstrated that 87 % of the treatment group was actively working after two years , as compared with only 41 % of the nontreatment comparison group . Moreover , about twice as many of the comparison group patients had additional spine surgery relative to the treatment group . The comparison group continued with an approximately five times higher rate of patient visits to health professionals in the second year as the treatment group . Also , treatment group reinjury rates were no higher than those expected in the general population , while nontreatment subjects had a higher incidence of reinjury . Finally , a small treatment " dropout " group did poorest of all , with results in almost all areas even worse than those of the comparison group patients The aim of this study was to evaluate an intensive , multidisciplinary functional restoration program for people with chronic low back pain . The program was compared to a non-treated control group in project A , and to less intensive treatment programs in project B. Both projects were r and omized and observer blinded . Two hundred and thirty-eight patients were included , 106 entering project A and 132 project B. All had had chronic low back disability of at least six months duration , with an average of one year 's sick leave due to low back pain over the last three years . Their average age was 41 years . The results at follow-up ( conducted four months after treatment , follow-up rate 90 % in project A and 86 % in project B ) showed that 67 % of the treated patients in project A were able to work compared to 28 % in the control group . In project B , 75 % of the patients treated in the functional restoration program were able to work , the corresponding numbers from the less intensive programs being 48 % and 40 % . Numbers of days of sick leave , contacts to the health-care system and pain- and disability-scores were significantly lower for the patients treated in the functional restoration program compared to the other groups in both projects . Functional restoration is more expensive to carry out , but the long-term benefits in form of reductions in pensions , sick leave and contacts to the health-care system , not to mention reduced pain for the patients , seems to justify this expenditure Study Design This was a study of a st and ardized functional restoration program that included 11 centers in saven states , involving 303 patients in the treatment group and 94 patients in the comparison group . Objective To illustrative the positive effect a functional restoration program has on return to work rates and work retention regardless of previous surgical intervention . Summary of Background Data Data were obtained from the initial and discharge evaluations as well as at 6− and 12-month follow-up . Methods Patients received a st and ardized work capacity assessment upon entrance and were recommended to the program if they adhered to specific entrance criteria . Treatment patients received the same evaluation at discharge . Results Significant improvement in functional abilities , actual return to work , and work retention were noted in the treatment group regardless of treatment intervention . Conclusions This study demonstrated improved return to work rates and work retention with surgical and nonsurgical patients after their participation in a functional restoration program & NA ; The effects of outpatient group cognitive therapy , relaxation training , and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared . One‐hundred and two mildly disabled chronic low back pain patients were assigned r and omly to a waiting‐list ( WL ) control condition and the 3 treatments . Patient self‐report and observational measures were obtained pretreatment and post‐treatment for all conditions , and at 6‐ and 12‐month follow‐ups for the treatment conditions . Pain intensity decreased significantly pre‐ to post‐treatment for patients in all 3 treatment conditions , but not the WL condition . Depressive symptoms and disability improved significantly in all conditions ( including the waiting list ) from pretreatment to post‐treatment , with no statistically significant differences among treatments . At both follow‐ups , all 3 treatment groups remained significantly improved from pretreatment , with no statistically significant differences between treatments & NA ; This study reports a 9–18 month follow‐up of a r and omised controlled trial of pain management programmes for chronic , non‐malignant pain . Twenty‐two in patients , 18 out patients and 12 control subjects completed the follow‐up assessment s. Significant treatment effects were demonstrated by the inpatient group on pain ratings , the Pain Behaviour Checklist , and General Health Question naire , with similar effects demonstrated by the outpatient group on the former 2 measures . The findings were confounded by higher inpatient scores at pretreatment , in comparison with the 2 other conditions . There was a high drop‐out rate of subjects , particularly from the control condition which illustrates the limitations of controlled group design s in this area . Analgesic use , activity levels and pain ratings were also evaluated using the criteria for ‘ success ’ described by Malec et al. ( 1981 ) . Results indicated that 68 % of in patients , 61 % of out patients and 21 % of control subjects met all 3 criteria . Both treatment programmes were effective in returning patients to paid employment , whilst 3 control group patients gave up work . The cost‐benefit implication s of these changes are discussed . We conclude that pain management programmes contribute substantially to the rehabilitation of chronic pain sufferers OBJECTIVE To evaluate a progressive fitness programme for patients with chronic low back pain . DESIGN Single blind r and omised controlled trial . Assessment s were carried out before and after treatment by an observer blinded to the study and included a battery of vali date d measures . All patients were followed up by postal question naire six months after treatment . SETTING Physiotherapy department of orthopaedic hospital . SUBJECTS 81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy . The patients were r and omly allocated to a fitness programme or control group . INTERVENTION Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care . Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool . RESULTS Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index ( P < 0.005 ) , pain reports ( sensory P < 0.05 and affective P < 0.005 ) , self efficacy reports ( P < 0.05 ) , and walking distance ( P < 0.005 ) . No significant differences between the groups were found by the general health question naire or question naire on pain locus of control . A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months . CONCLUSION There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain . Further clinical trials , however , need to be established in other centres to confirm these findings A prospect i ve r and omized study of 542 injured workers with continuing pain compared 271 workers who were treated at either one of two clinics that provided functional restoration with a control group of 271 subjects . Chronic pain was caused by low back injury in 78 % of patients ; 79 % of those treated were at work 12 months after completion of treatment compared with 78 % of the control subjects . When the patients were divided into subsets , based on the accident date and followed monthly , the duration of absence from work , the compensation costs , the disability award costs , and the total costs were less for those treated than the control subjects , but these were not statistically significant . Using the difference in total costs as a measure of relative success , back injuries had better results than other injuries in this study A group of 109 patients with unilateral low back pain for over three months were r and omised to receive one of three types of injection treatment : cortisone and local anaesthetic injected into two facet joints ( 28 ) , the same mixture around two facet joints ( 39 ) , or physiological saline into two facet joints ( 42 ) . The effect of the treatment was evaluated in relation to work attendance , pain , disability and movements of the lumbar spine . Patients were examined one hour and two and six weeks after treatment and also completed a question naire after three months . A significant improvement was observed in work attendance , pain and disability scores , but this was independent of the treatment given and movements of the lumbar spine were not improved . Of the 70 patients with initial pain relief after injection , 36 % reported persisting benefit at the three month follow-up , independent of the mode of treatment given . We conclude that facet joint injection is a non-specific method of treatment and the good results depend on a tendency to spontaneous regression and to the psychosocial aspects of back pain Chronic back/joint pain patients participated in a comparative study of relaxation and operant therapies for chronic pain . Patients were r and omly assigned to : ( 1 ) a waiting-list control , or to either ( 2 ) an applied relaxation , or ( 3 ) an applied relaxation plus operant conditioning treatment programme . Waiting patients were subsequently r and omly assigned to active treatment . The results indicated that the treatment groups tended to do significantly better than the waiting-list control group for pain , medicine use , activity , and depression , but there were few clear differences between the treatment groups . Applied relaxation plus the operant programme was significantly better than relaxation for medicine reduction , and applied relaxation was better than relaxation and operant conditioning for a patient evaluation of reaching treatment goals . Within-group and single-subject analyses indicated that there were significant improvements between pre- and post-tests for the treatment groups , but not for the waiting-list control group . Follow-up data indicated maintenance , and that applied relaxation had significantly lower pain ratings than applied relaxation plus operant conditioning . Taken as a whole , the results show that applied relaxation can produce significant decreases in pain , and that the addition of an operant programme does not improve pain reductions , but does tend to improve results with activity and especially medicine intake variables The results of a r and omized clinical trial can be reported using relative and /or absolute estimators of treatment effect . These various measures convey different information , and the choice can influence the physician 's appreciation of the size of treatment effect and , subsequently , treatment decisions . We compare the estimators with respect to the clinical ly relevant information conveyed to physicians , and identify which clinical questions can and can not be answered directly by each . We also identify opportunities for misinterpretation when one estimator is substituted for another , or when an estimator is mislabeled . Clinical ly important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement , relative risk reduction , and risk difference and its reciprocal , number needed to treat . This is true of estimates of treatment effect derived from a single trial and also from meta- analysis of a group of trials . Because the control group 's risk affects the numerical value of the odds ratio , the odds ratio can not substitute for the risk ratio in conveying clinical ly important information to physicians . This is especially important when large treatment effects are shown in trials carried out in population s at high baseline risk Study Design The authors conducted a controlled clinical trial with 1-year follow-up to define the effectiveness of an intensive physical and psychosocial training program on patients with low back pain . Summary of Background Data The intervention group included 152 patients ( mean age 40.5 yr , Million index 45.1/100 ) , and the reference group included 141 patients ( mean age 40.4 yr , Million index 44.5/100 ) . Methods The progressive intervention program consisted of intensive physical training and psychosocial activation . The outcomes were physical and psychosocial measures , the pain and disability index ( Million ) , sick leaves , and occupational h and icap . Results The intervention was more efficient with respect to physical measures and pain and disability index . There were only mild or no differences in changes between the study groups in psychology variables , sick leaves , or retirement . Conclusions The intervention program could improve physical disability , but to improve occupational h and icap , activities of the whole society ( social legislation , labor market policy ) are needed Inpatient and outpatient treatments were compared with a control intervention in 288 men and 168 women , aged 35 - 54 , who were at work , but suffered from chronic or recurrent low back pain . Physical measurements and back pain assessment s were carried out before the intervention and at a 3-month follow-up . Physical fitness improved most in the in patients , but the out patients did not differ from the controls . Correlations between back pain and physical measurements indicated that increase of lumbar and hip mobility was more important than increase of trunk strength for subjective progress in these patients . Increased trunk extension strength correlated significantly with subjective progress in women , who also had higher correlations between improved physical fitness and progress than men In a r and omized , observer-blind trial , 150 men and women , aged 21 - 64 years , with chronic/subchronic low-back pain , followed one of these three treatment regimens : 1 ) intensive , dynamic back-muscle exercises ; 2 ) conventional physiotherapy , including isometric exercises for the trunk and leg muscles ; and 3 ) placebo-control treatment involving semihot packs and light traction . Eight treatment sessions were given during the course of 4 weeks , each session lasting 1 hour . The short-term effect was evaluated at the end of the treatment period and 1 month later , and the long-term effect at 6 and 12 months . The evaluations included recording of changes in pain level and assessment of overall treatment effect , which were indicated on visual interval scales . Subgroups of patients could be identified according to their treatment responses : physiotherapy was the superior treatment for the male participants , whereas the intensive back exercises appeared to be most efficient for the female participants . Patients with moderate or hard physical occupations tended toward a better response with physiotherapy , whereas intensive back exercises seemed most effective for those with sedentary/light job functions Patients with chronic disabling low-back pain have poor prospect s of returning to work . The authors tested a treatment program of functional restoration with behavioral support through 1 year prospect i ve observation of patients disabled for an average of 19 months without evidence of surgically correctable disease . Ninety patients were studied : 59 program graduates , five program dropouts , 17 patients denied program authorization by their Insurance carriers , and six crossover patients . Three patients were admitted but refused to participate in the treatment program . Initial demographic , physical , and self- assessment attributes were similar for all four groups . At year 's end , 81 % of program graduates , 40 % of the dropouts , and 29 % of those denied the program had returned to work . All six crossover patients were working 6 months after treatment . Program graduates showed significant improvements in self-assessed pain , disability , and depression , and in physical capacities after 3 weeks of treatment . These improvements were maintained through the year except for partial decreases in frequent lifting , cycling endurance , and isokinetic trunk extension strength . Functional restoration with behavioral support is an effective treatment for patients with chronic , disabling low-back pain , as measured by self- assessment s , physical capacities , and return to work Fifty-eight out patients with chronic low back pain were r and omly allocated to one of six experimental conditions . Four conditions were design ated as treatment conditions and two as control conditions . The four treatment groups consisted of : cognitive treatment ( either with or without relaxation training ) and behavioural treatment ( either with or without relaxation training ) . The cognitive and behavioural groups also received physiotherapy . The two control conditions consisted of : attention ( physiotherapy plus discussion sessions ) and no-attention ( physiotherapy-only ) conditions . All conditions , including the two controls , received the same physiotherapy back-education and exercise program . For the sample as a whole , improvements were obtained on measures of affective distress , functional impairment , medication use , pain-related dysfunctional cognitions and use of active coping strategies . These improvements were generally maintained at 6- and 12-month follow-ups . The combined psychological/physiotherapy treatment conditions improved significantly more than the physiotherapy-only conditions from pre to posttreatment on measures of pain intensity , self-rated functional impairment and pain-related dysfunctional cognitions . However , these differences were only weakly maintained at 6- and 12-month follow-ups . The behavioural conditions improved significantly more than the cognitive conditions from pre to posttreatment on the self-rated measure of functional impairment , but this difference was not maintained at 6- and 12-month follow-ups . Progressive relaxation training was found to make little contribution to either cognitive or behavioural treatments Study Design . Two r and omized , prospect i ve clinical trials involving 238 chronic low back disability patients were carried out . Results at 2‐year follow‐up are presented . Objectives . To compare the clinical outcomes of a multidisciplinary functional restoration program with a nontreated control group ( Project A ) and with two less intensive but different training programs ( Project B ) . Summary of Background Data . The effectiveness of functional restoration programs has not been firmly established . Results from trials carried out in the United States differ from those in trials conducted in other countries . Only a few of these studies have been carried out as prospect i ve and r and omized clinical studies . Methods . Two hundred thirty‐eight patients with chronic low back disability of at least 6 months ' duration were included . There were 106 patients in project A and 132 patients in project B. Two years after completion of treatment , patients were mailed a question naire that included questions regarding their work status , pain and disability levels , number of sick leave days , number of medical care contacts , medication use , physical activity levels , and subjective overall assessment of their " back life situation . " Results . Patients in both studies were comparable at inclusion , except that patients in Project A were recruited from all of Denmark , whereas those in Project B were from the greater Copenhagen area . Thirteen patients did not report for treatment after r and omization . Of the remaining 225 patients , 20 ( 9 % ) did not complete treatment . The question naire response rate was 94 % . In Project A , those patients receiving treatment ( functional restoration ) reported significantly less contact with the health care system , fewer sick leave days , and a less disabled life style during the follow‐up period , compared with reports of patients in the control group . Other effect parameters did not demonstrate a significant difference between the two groups . In Project B , all effect parameters reported , except leg pain and medication usage , were significantly in favor of functional restoration , compared with reports from the less intensively treated groups . Conclusions . The functional restoration program seems effective in various parameters compared with the less intensive programs , but the differences in outcome in the two parallel studies indicate the necessity of testing a treatment program in different setting s , in that the statistical variation may be a major factor in results of different studies & NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems OBJECTIVE Musculoskeletal disorders ( MSD ) are a leading cause of morbidity in the population , yet their prominence seems to be insufficiently appreciated . We describe the ranking compared with other major body systems of the prevalence of MSD , including arthritis and rheumatism , and back/neck disorders , as a cause of chronic health problems , longterm disability , restricted activity days , consultation with health professionals , and use of both prescription and nonprescription drugs . METHODS We analyzed data from the 1990 Ontario Health Survey , a stratified r and om sample of the household dwelling population in Ontario , based on 45,650 individuals aged 16 years and over . RESULTS MSD ranked first in prevalence as the cause of chronic health problems , longterm disabilities , and consultations with a health professional and ranked 2nd for restricted activity days and use of both prescription and nonprescription drugs . No other body systems ranked invariably within the top 2 ranks for the morbidity indices examined . Even when compared to other major disease groups , arthritis and rheumatism ranked consistently in the top 3 and back/neck disorders also ranked high . MSD were mentioned as a reason for 40 % of all chronic conditions , 54 % of all longterm disability , 24 % of restricted activity days and almost 20 % of health care utilization . The impact of MSD was even greater in the 65 and over age group . CONCLUSIONS MSD have a major role in the health profile of the population . This high burden of illness should be considered in planning health care services and setting research priorities Abstract A functional restoration ( FR ) program , dealing with a combination of intensive physical and ergonomic training , psychological pain management , and patient education , was tested in two r and omized , parallel group studies . In one of these patients following the FR program were compared with a non-treated control group ( project A ) , and in the other with patients on two less intensive treatment programs ( project B ) . A total of 238 chronic low back pain patients participated in the two studies , 106 entering project A and 132 project B. Patients from the two projects were comparable except that the patients in project A were recruited from all over the country , whereas patients in project B all were living in and around Copenhagen . Thirteen patients never started any treatment , and 20 patients ( 9 % ) dropped out during the treatment period . Of the 207 who completed treatment , 89 % returned a mailed question naire 5 years later . This was the case for 55 % of the drop-outs . The questions referred to work situation , pain level , activities of daily living , days of sick leave , contact with health care professionals , physical activity , use of medication , and a subjective overall assessment . The results show that in project A the treated group reported significantly fewer contacts with the health care system and significantly fewer days of sick leave over the 5-year follow-up period compared to the control group . In all other parameters , including work ability , there was no statistically significant difference between the two groups . In project B , patients treated in the FR program did significantly better in most measured parameters , except in leg pain , use of pain medication and sport activity , where no significant differences were found between groups . The overall result shows a positive long-term effect of the FR program , but it also shows the necessity of testing a given treatment in different projects and design s , among other things due to statistical variations Patients with nonspecific mechanical low back pain ( n = 103 ) , examined by an orthopaedic surgeon and a social worker , were r and omized to an activity group ( n = 51 ) and a control group ( n = 52 ) . Patients with defined orthopaedic , medical , or psychiatirc diagnoses were excluded before r and omization . No patients were excluded due to place of birth or difficulties in speaking or underst and ing the Swedish language . The purpose of the study was to compare mobility , strength and fitness after traditional care and after traditional care plus a grade d activity program with a behavioral therapy approach . A grade d activity program , with a behavioral therapy approach was given under the guidance of a physical therapist . The endpoint of the grade d activity program was return to work . This program significantly increased mobility , strength , and fitness more than could be explained by only a time recovery effect , especially in males . The patients in the activity group returned to work earlier than did the patients in the control group . Spinal rotation , abdominal muscle endurance time and lifting capacity were significantly correlated to rate of return to work . Traditional care plus a grade d activity program were superior to only traditional care , evaluated in terms of mobility , strength and fitness . The grade d activity program proved to be a successful method of restoring occupational function and facilitating return to work in subacute low back pain patients . The patients in the grade d activity program learned that it is safe to move , while regaining function A treatment- outcome study was conducted to study the impact of behavior and physical therapy on components of the chronic low back pain syndrome . Eighteen patients received behavior therapy and 15 patients received physical therapy . All patients had at least a 6-month history of seeking treatment for chronic low back pain . Prior to treatment patients were assessed in four principal areas of functioning : ( 1 ) physical abilities ; ( 2 ) current physical functioning ; ( 3 ) psychological and psychosocial functioning ; and ( 4 ) pain intensity and pain perception . Treatments were conducted in a group ( five to eight patients ) outpatient setting . Both behavior therapy and physical therapy groups met for 10-weekly sessions , each lasting 2 hr . Behavior therapy was design ed to address the environmental , social , and emotional components of the low back pain syndrome as well as the depression and decreased activity that result from chronic low back pain . Physical therapy was based upon traditional rehabilitation theory and was design ed to improve low back function . Patients were reevaluated at posttreatment , 6 months , and 1 year . The results showed a general improvement for patients in both groups and a few treatment-specific differences in outcome measures Summary Several new studies have indicated that an active approach to patients with chronic disabling low back pain ( LBP ) seems effective . Some of these studies emphasize the importance of dealing with the patient 's total situation in comprehensive multidisciplinary programs — the bio-psycho-social model . However , these programs are expensive . The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of : ( 1 ) return-to-work rate , ( 2 ) days of sick leave , ( 3 ) health-care contacts , ( 4 ) pain and disability scores , and ( 5 ) staying physically active . The subjects included 132 patients r and omized to the study , of whom 123 started one of the treatment programs . They had all had at least 6 months of chronic LBP . The patients were r and omized into one of three programs : group 1 — a full-time , intensive 3-week multidisciplinary program , including active physical and ergonomic training and psychological pain management , followed by 1 day weekly for the subsequent 3 weeks ; group 2 — active physical training , twice a week for 6 weeks , for a total of 24h ; group 3 — psychological pain management combined with active physical training , twice a week for 6 weeks , also for a total of 24h . The results presented here are based on data collected 4 months following treatment , which shows an 86 % response rate . The initial examination and the follow-up evaluation were performed by a blinded observer . The results show that 4 months after treatment , the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate , health-care contacts , pain and disability scores , and staying physically active . In conclusion , it seems that although the multidisciplinary program is initially expensive compared to the less intensive programs , the savings in sick pay , early retirement pensions , and health care contacts make it economically worthwhile . Long-term follow-up will show whether this effect continues The aim of this prospect i ve study was to examine the one-year postoperative results in patients operated on for lumbar disc herniation r and omized in two groups : one with comprehensive rehabilitation and the other taken care of by normal care facilities . A total of 212 patients without any previous spinal operations comprised the final study group . The physiatrist , the surgeon , the social worker , and the psychologist performed the h and icap evaluation according to the occupation h and icap scales of the WHO . The h and icap was evaluated for two phases : before the onset of acute sciatica leading to operation and one year after operation . No significant differences in h and icap distribution between the intervention and normal care groups were seen . The postoperative h and icap correlated highly significantly with preoperative h and icap for both groups . More than half ( 57 % ) of all the patients returned to work within two months of the operation . The amount of sick leaves did not differ significantly between the intervention and normal care groups . A total of 15 persons ( 7 % ) retired during the postoperative year Cognitive behavioral treatment has been incorporated into st and ard medical treatment procedures in German pain centers . Acceptance of the treatment by patients and outcome in terms of pain , coping , and disability was investigated . Components of the psychological treatment are education , relaxation and imagery , modifying thoughts and feelings , enhancement of pleasant activities , and training of good postural habits . The program was conducted in a group setting in accordance with a treatment manual and consists of 12 weekly 2.5-h sessions . A two-factor experiment with repeated measures on one factor was applied . Ninety-four consecutive patients with low-back pain were r and omly assigned to an experimental group having a combined medical and cognitive-behavioral treatment , or to a control group with medical treatment only . Assessment s were taken pre-treatment , post-treatment , and --in the treated group only -- at a 6-months follow-up . At each assessment , patients kept a pain diary over a period of 4 weeks , and filled in self-report question naires . The sample consisted of 36 experimental and 40 control subjects at post-treatment . Experimental subjects reported less pain , better control over pain , more pleasurable activities and feelings , less avoidance and less catastrophizing . In addition , disability was reduced in terms of social roles , physical functions and mental performance . The results were maintained at follow-up . Patients who only received medical treatment showed little improvement . Data indicate that the program meets the needs of the patients and should be continued & NA ; Current conceptions of chronic pain clearly suggest that proper care at the acute stage should prevent the development of chronic problems . Patients ( 198 ) seeking help for acute musculoskeletal pain ( MSP ) , e.g. , back and neck pain participated in two studies of the effects of an Early Active intervention which underscored ‘ well ’ behavior and function compared to a Treatment as Usual control group . The quantity of the Early Active treatment was a median of 1 doctor 's appointment and 3 meetings with a physical therapist . Study I concerned patients with a prior history of sick‐listing for MSP , while study II involved patients with no prior history of MSP . Treatment satisfaction , pain experience , activities and sickness absenteeism were assessed before , after and at a 12‐month follow‐up . In study I ( patients with a history of MSP ) , the results showed significant improvements for both groups , but virtually no differences between the groups . Similarly , in study II ( no history of MSP ) both groups demonstrated significant improvements e.g. , for pain intensity and activity levels . However , the Early Active treatment result ed in significantly less sick‐listing relative to the control group . Moreover , the risk of developing chronic ( > 200 sick days ) pain was 8 times lower for the Early Activation group . This investigation shows that relatively simple changes in treatment result in reduced sickness absenteeism for ‘ first‐time ’ sufferers only . Consequently , the content and timing of treatment for pain appear to be crucial . Properly administered early intervention may therefore decrease sick leave and prevent chronic problems , thus saving considerable re sources & NA ; Forty‐five low back pain patients were r and omly assigned to either a st and ard inpatient rehabilitation program or the st and ard program with additional psychological components . The st and ard program emphasized education , support , and physical reconditioning through exercise . Patients receiving the psychological program were given additional training in relaxation and other coping skills and received contingent reinforcement for exercise . Both programs included reduction of medication intake and an emphasis on family involvement after discharge . Measures of functional status were taken prior to the program , at discharge from the 3‐week inpatient program , and at a 6‐month follow‐up appointment . These data revealed that patients improved their overall functioning at discharge and maintained these gains at the follow‐up assessment . A similar pattern of findings was obtained for self‐reported pain and interference . Furthermore , 81 % of the patients had returned to work or were engaged in active job retraining by the follow‐up . Using a conservative measure of full‐time return to the same or an equivalent job , 57 % were employed by the follow‐up . Patient improvement , however , was not differentially affected by treatment group assignment , suggesting that the psychological treatment failed to add to the effectiveness obtained by the st and ard rehabilitation program . Results are discussed in the context of improving patient outcomes from rehabilitation for low back pain The “ Back-Pain Institute ” at Sundsvall offers an advanced rehabilitation program to people with long-st and ing back pain . This program has been evaluated in a controlled prospect i ve study . Data were gathered from question naires mailed on three occasions , from the sick insurance office and from the bureau of employment . The effects of the Institute 's course on the vocational situation were small . The only significant difference between the experimental group and the control group was in the level of income . Significantly more persons in the experimental group had begun to train their back and significantly more individuals in the experimental group believed that by using the correct working technique they could prevent back pain . No significant changes were found with regard to the subjective feeling of pain BACKGROUND Americans with low back pain have been helped to return to work by multidisciplinary intensive treatment programs . Whether this treatment method will succeed in countries with a more generous social welfare system , where the incentive to return to work might be less , is not proven . OBJECTIVES To evaluate a Danish program of functional restoration combined with behavioral support . METHODS Patients who had experienced at least 6 months of disabling low back pain were r and omly assigned to either a 3-week intensive treatment program ( n = 55 ) or an untreated control group ( n = 51 ) . RESULTS Of the 106 patients r and omized , 94 ( 89 % ) returned for a 4-month follow-up visit . At that time , 29 ( 64 % ) of the 45 treated patients were able to work , compared with 14 of 49 ( 29 % ) in the control group . The treated patients had used fewer days of sick leave ( P < .02 ) , had contacted health care . professionals fewer times ( P < .001 ) , and had lower pain and disability scores . CONCLUSIONS Although such programs are expensive , they can reduce pension expenditures , sick leave days , health care contacts , and pain At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as & NA ; Inpatient and outpatient cognitive behavioural pain management programmers for mixed chronic pain patients were compared . Patients were r and omly allocated to the 4 week inpatient programme or to the 8 half day per week outpatient programme , or to a waiting list control group . Staff , teaching material s , and setting were the same for the two treatment groups . Patients were assessed pre‐treatment , and at 1 month after discharge , and treated patients also at 6 months and 1 year after discharge , by assessors blind to treatment group ; assessment s included physical , functional and psychological measures , and medication use . In total , 121 mixed chronic pain patients ( mean age 50 years ; mean chronicity 8.1 years ) were included in the study , following medical examination to ensure that no further medical treatment was appropriate . There was no change in the control group ; in patients and out patients , comparable before treatment , both made significant improvements in physical performance and psychological function , and reduced medication use . In patients made greater gains , and maintained them better at 1 year ; they also used less health care than out patients . There were no outst and ing predictors of improvement other than treatment group |
2,310 | 30,321,454 | There is currently insufficient evidence to determine the effects of parent-mediated interventions for improving the language and communication of children with Down syndrome . | BACKGROUND Communication and language development are areas of particular weakness for young children with Down syndrome .
Caregivers ' interaction with children influences language development , so many early interventions involve training parents how best to respond to their children and provide appropriate language stimulation .
Thus , these interventions are mediated through parents , who in turn are trained and coached in the implementation of interventions by clinicians .
As the interventions involve a considerable commitment from clinicians and families , we undertook this review to synthesis e the evidence of their effectiveness .
OBJECTIVES To assess the effects of parent-mediated interventions for improving communication and language development in young children with Down syndrome .
Other outcomes are parental behaviour and responsivity , parental stress and satisfaction , and children 's non-verbal means of communicating , socialisation and behaviour . | PURPOSE The purpose of this study was to compare the effects of enhanced milieu teaching ( EMT ) implemented by parents and therapists versus therapists only on the language skills of preschool children with intellectual disabilities ( IDs ) , including children with Down syndrome and children with autism spectrum disorders . METHOD Seventy-seven children were r and omly assigned to 2 treatments ( parent + therapist EMT or therapist-only EMT ) and received 36 intervention sessions . Children were assessed before , immediately after , 6 months after , and 12 months after intervention . Separate linear regressions were conducted for each st and ardized and observational measure at each time point . RESULTS Parents in the parent + therapist group demonstrated greater use of EMT strategies at home than untrained parents in the therapist-only group , and these effects maintained over time . Effect sizes for observational measures ranged from d = 0.10 to d = 1.32 favoring the parent + therapist group , with the largest effect sizes found 12 months after intervention . CONCLUSION Findings from this study indicate generally that there are benefits to training parents to implement naturalistic language intervention strategies with preschool children who have ID and significant language impairments The outcomes of a r and omized clinical trial of a new behavioral family intervention , Stepping Stones Triple P , for preschoolers with developmental and behavior problems are presented . Forty-eight children with developmental disabilities participated , 27 r and omly allocated to an intervention group and 20 to a wait-list control group . Parents completed measures of parenting style and stress , and independent observers assessed parent-child interactions . The intervention was associated with fewer child behavior problems reported by mothers and independent observers , improved maternal and paternal parenting style , and decreased maternal stress . All effects were maintained at 6-month follow-up OBJECTIVE : Early interventions for toddlers with expressive and receptive language delays have not result ed in positive expressive language outcomes . This r and omized controlled trial tested the effects on language outcomes of a caregiver-implemented communication intervention targeting toddlers at risk for persistent language delays . METHODS : Participants included 97 toddlers , who were between 24 and 42 months with language scores at least 1.33 SDs below the normative mean and no other developmental delays , and their caregivers . Toddlers were r and omly assigned to the caregiver-implemented intervention or a usual-care control group . Caregivers and children participated in 28 sessions in which caregivers were taught to implement the intervention . The primary outcome was the Preschool Language Scale , Fourth Edition , a broad-based measure of language . Outcome measurement was not blinded . RESULTS : Caregivers in the intervention improved their use of all language facilitation strategies , such as matched turns ( adjusted mean difference , intervention-control , 40 ; 95 % confidence interval 34 to 46 ; P < .01 ) . Children in the intervention group had significantly better receptive language skills ( 5.3 ; 95 % confidence interval 0.15 to 10.4 ) , but not broad-based expressive language skills ( 0.37 , 95 % confidence interval −4.5 to 5.3 ; P = .88 ) . CONCLUSIONS : This trial provides preliminary evidence of the short-term effects of systematic caregiver instruction on caregiver use of language facilitation strategies and subsequent changes in children ’s language skills . Future research should investigate the ideal dosage levels for optimizing child outcomes and determine which language facilitation strategies are associated with specific child outcomes . Research on adaptations for families from culturally and linguistically diverse background s is needed PURPOSE The authors examined ( a ) whether dose frequency of milieu communication teaching ( MCT ) affects children 's canonical syllabic communication and ( b ) whether the relation between early canonical syllabic communication and later spoken vocabulary is mediated by parental linguistic mapping in children with intellectual disabilities ( ID ) . METHOD The authors drew on extant data from a recent differential treatment intensity study in which 63 toddlers with ID were r and omly assigned to receive either five 1-hr MCT sessions per week ( i.e. , daily treatment ) or one 1-hr MCT session per week ( i.e. , weekly treatment ) for 9 months . Children 's early canonical syllabic communication was measured after 3 months of treatment , and later spoken vocabulary was measured at posttreatment . Midpoint parental linguistic mapping was measured after 6 months of treatment . RESULTS A moderate-sized effect in favor of daily treatment was observed on canonical syllabic communication . The significant relation between canonical syllabic communication and spoken vocabulary was partially mediated by linguistic mapping . CONCLUSIONS These results suggest that canonical syllabic communication may elicit parental linguistic mapping , which may in turn support spoken vocabulary development in children with ID . More frequent early intervention boosted canonical syllabic communication , which may jump-start this transactional language -learning mechanism . Implication s for theory , research , and practice are discussed Parents of children with a developmental disability require tailored parenting support , as their families have special needs and are at risk of increased burden . The aim of this study was to evaluate the efficacy of the Stepping Stones Triple P seminars , a brief group intervention for parents of a child with a disability . There were two seminars that presented parenting strategies to improve both child behavior and parenting variables implicated in the development and maintenance of child problem behavior . Fifty-three parents participated in this r and omized controlled trial . Each had a child , aged two to ten , with a disability . The results indicated significant reductions in child behavior problems , the use of dysfunctional parenting styles , and parental conflict reported by parents in the intervention group compared to a waitlist group . The results were maintained at 3-month follow-up and there was evidence of a sleeper effect for parenting confidence . This study demonstrated that the seminars provide a promising intervention for parents of children with a disability . Limitations and implication s for future research are also discussed Routines-based early intervention ( RBEI ) for children with or at risk for developmental delay encourages collaboration between professionals and families to enhance children 's participation in family routines with family-selected goals . We conducted the first single-blinded r and omized control trial to examine the effectiveness of a 6-month RBEI vs. traditional home visiting ( THV ) , which uses a curriculum focused on children 's developmental domains . Thirty-one families with children aged 5 - 30 months ( mean age 17.4 months ) with or at risk for developmental delay were r and omly assigned to an RBEI group ( n=15 ) or a THV group ( n=16 ) . The enrolled children were evaluated using the Chinese version of Pediatric Evaluation of Disability Inventory ( PEDI-C ) and the Comprehensive Development Inventory for Infants and Toddlers ( CDIIT ) at 5 time points . Two-way mixed analysis of variance ( ANOVA ) was used to examine the group by stage interactions . Goal Attainment Scaling ( GAS ) and the Canadian Occupational Performance Measure ( COPM ) were applied to explore between-group differences on individualized goal achievement . PEDI-C showed that the RBEI group had a faster progress rate in self-care functions and independence in social functions in the first 3 months of intervention and at the 6-month follow-up . The RBEI group also scored higher on the GAS in the first 3 months of intervention . However , between-group differences in changes in the developmental domains on the CDIIT were not significant . Thus , RBEI was more effective than THV in promoting functional outcomes and reaching family-selected goals , while both interventions allowed equal improvement in developmental domains The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Family systems theory posits that the relative effectiveness of early interventions will vary depending on various aspects of the family . This study tested whether maternal responsivity would predict the extent to which Prelinguistic Milieu Teaching ( PMT ) facilitated generalized intentional communication better than a contrast treatment that was conducted in a small group by a responsive adult ( i.e. , Responsive Small Group , RSG ) . Fifty-eight children with developmental disabilities in the prelinguistic communication period of development were r and omly assigned to one of the two staff-implemented treatment groups . Thirty were assigned to RSG ; 28 were assigned to PMT . Mothers were kept naive to the intervention methods , hypotheses , and measures . In families with mothers who responded to a high percentage of the children 's communication acts at the pre-treatment period , the children in the PMT group used more frequent intentional communication in post-treatment generalization sessions with a trainer and mothers than did children in the RSG group . In the families with mothers who responded to fewer than 39 % of their children 's communication acts , children in the RSG intervention used more frequent intentional communication in post-treatment generalization sessions with the mothers than did children in the PMT intervention . Other family variables and no child variables that we measured could account for these findings AIM This study aim ed to evaluate the efficacy of a parent education program , the Happy Parenting program , for Chinese preschool children with developmental disabilities . METHODS This study adopted r and omized controlled trial design without blinding . Participants were r and omized into intervention group ( n=62 ) who were offered the Happy Parenting program delivered by educational psychologists and trainee educational psychologists , and a control group ( n=57 ) who were offered a parent talk after the intervention group had completed treatment . Parent participants were requested to complete question naires on their children 's behavior , their parenting stress , and discipline strategies . RESULTS Analysis was by intention-to-treat . The results indicated significant decrease in child problem behaviors , parenting stress and dysfunctional discipline strategies in the intervention group at post-intervention . CONCLUSION This study provided promising evidence on the effectiveness of a parent education program , the Happy Parenting program , for Chinese preschool children with developmental disabilities We design ed a parent-directed home-visiting intervention targeting socioeconomic status ( SES ) disparities in children 's early language environments . A r and omized controlled trial was used to evaluate whether the intervention improved parents ' knowledge of child language development and increased the amount and diversity of parent talk . Twenty-three mother-child dyads ( 12 experimental , 11 control , aged 1;5 - 3;0 ) participated in eight weekly hour-long home-visits . In the experimental group , but not the control group , parent knowledge of language development increased significantly one week and four months after the intervention . In lab-based observations , parent word types and tokens and child word types increased significantly one week , but not four months , post-intervention . In home-based observations , adult word tokens , conversational turn counts , and child vocalization counts increased significantly during the intervention , but not post-intervention . The results demonstrate the malleability of child-directed language behaviors and knowledge of child language development among low-SES parents PURPOSE To evaluate the longitudinal effects of a 6-month course of responsivity education (RE)/prelinguistic milieu teaching ( PMT ) for young children with developmental delay . METHOD Fifty-one children , age 24 - 33 months , with fewer than 10 expressive words were r and omly assigned to early-treatment/no-treatment groups . All treatment was added as a supplement to services that the children received in the community . Follow-up data were collected 6 and 12 months after the conclusion of the initial 6-month treatment/no-treatment conditions . RESULTS No effects of this treatment were detected 6 or 12 months after the conclusion of the initial treatment condition . CONCLUSIONS M. E. Fey et al. ( 2006 ) reported that 6 months of RE/PMT led to a significant treatment effect in the use of intentional communication in 1 of 2 communication sampling context s. This finding , combined with evidence from other studies , suggests that RE/PMT may be applied clinical ly at low intensity with the expectation of medium-sized effects on children 's rate of intentional communication acts over the short term . The results of the present study , however , provide no evidence for the anticipated longer term benefits of this intervention . Further investigation of the approach at higher intensity levels and for longer periods of time is warranted This article presents results of a r and omized controlled trial examining the efficacy of Parent – Child Interaction Therapy ( PCIT ) for treating disruptive behaviors of young children ( ages 3 to 6 ) with mental retardation ( MR ) and comorbid oppositional defiant disorder . Thirty families were r and omly assigned to an immediate treatment ( IT ) or waitlist ( WL ) control group . Results indicated that IT mothers interacted more positively with their children after treatment than WL mothers , and their children were more compliant after treatment . On parent-report measures , IT mothers reported fewer disruptive behaviors at home and lower parenting stress related to difficult child behavior than WL mothers after treatment . Whether evidence -based treatments for disruptive behavior require modification before application to children with MR is discussed This study assesses the longitudinal effects of an original early intervention programme on the adaptation of parents of children with a disability ( Down syndrome and cleft lip/palate , i.e. DS and CLP ) . Variations in the effects of the programme according to the time of measurement , the type of disability and parent 's gender are also examined . Globally , the results show a better adaptation among parents who participated in the intervention programme compared to those who did not participated in the programme . These parents had lower levels of parental stress , they had more positive perceptions and attitudes concerning their child 's disability and their parental situation , they were more confident in their own re sources and the help they could receive from others , they had lower levels of emotional distress , anxiety and depression and they perceived more emotional support from their spouse . In general , these gains were maintained throughout the year when the children were between six and 18 months of age , they were relatively similar for parents of children with DS and parents of children with CLP , as well as for mothers and fathers The interactive model of language intervention instructs parents to use techniques that promote reciprocal social interactions and facilitate the development of communication and language abilities . In this evaluation study , 32 mothers and their preschool-age children with developmental delays were r and omly assigned to treatment and control ( delayed treatment ) groups . Consistent with the interactive model , mothers in the treatment group became more responsive , less directive , and provided clearer linguistic models . Furthermore , these changes were maintained for at least 4 months after intervention , and involvement in the parent-centered intervention program did not increase maternal stress . More important , these changes were accompanied by concomitant increases in children 's use of vocal turns . Contrary to predictions , developmental improvements in children 's communicative and linguistic abilities were comparable in both groups . Findings suggest that an interactive model may afford a useful adjunct to other intervention approaches by instructing parents on how to promote children 's use of existing abilities , but an interactive model may have no effect on language acquisition of at least some children with developmental delays This study examined the specificity of outcome in a group behavior modification training program for parents of developmentally disabled children . Fifteen families were r and omly assigned to either a Parents as Teachers or Parents as Advocates course . Measures of behavior modification knowledge and skill , and advocacy knowledge and skill were administered to all subjects pre and post training . On three of the four outcome measures , subjects demonstrated gains that were specific to their training program . The effects of nonspecific factors appear to have been minimal Guidelines suggest that all children with Down 's syndrome have hearing testing on a regular basis . Since 2004 , the ear , nose and throat ( ENT ) , audiology and education services have conducted a joint clinic for annual ENT health and hearing surveillance of all preschool children with Down 's syndrome in Greater Glasgow . The aim of this study is to report the prevalence of ENT problems in this well-defined birth cohort , and the proportion of children for whom ENT surgery is required . A prospect i ve data base has been kept since 2004 , detailing the ENT health status of every child attending the community-based surveillance clinic . Between September 2004 and September 2008 , 87 preschool ( aged 9 months to 6 years ) children with Down 's syndrome were sent appointments for the clinic . Of these , 48 ( 55 % ) were female and 39 were male . Data were available for 79 ( 91 % ) . Over the course of the study , 37 % were listed for surgery at some point , either adenotonsillectomy for obstructive symptoms or grommet insertion for otitis media with effusion ( OME ) . The prevalence of OME was 93 % at age 1 , falling to 68 % by age 5 . None had significant sensorineural hearing impairment . Obstructive symptoms were also common , with 79 % of children having either currently symptomatic upper airways obstruction or a history of adenotonsillectomy by age 5 . One child had laryngomalacia and two had symptomatic congenital subglottic stenosis . The prevalence of ENT problems in these children is high . Surgical intervention is frequently required . We advocate a proactive approach of regular ENT and audiology surveillance leading to early intervention , with the aim of maximizing health and educational achievement in the long term This study explores the effects of training parents to administer focused stimulation intervention to teach specific target words to their toddlers with expressive vocabulary delays . Twenty-five mothers and their late-talking toddlers were r and omly assigned to treatment and delayed-treatment ( control ) groups . Vocabulary targets were individually selected for each toddler based on the child 's phonetic repertoire and parent report of vocabulary development . Following treatment , mothers ' language input was slower , less complex , and more focused than mothers in the control group . Concomitantly , their children used more target words in naturalistic probes , used more words in free-play interaction , and were reported to have larger vocabularies overall as measured by parent report . In addition , the treatment had an effect on language development-children in the experimental group used more multiword combinations and early morphemes than children in the control group . The implication s of these results are discussed with regard to the role of focused stimulation intervention for children with expressive vocabulary delays Given the strong association between early behavior problems and language impairment , we examined the effect of a brief home-based adaptation of Parent-child Interaction Therapy on infant language production . Sixty infants ( 55 % male ; mean age 13.47±1.31 months ) were recruited at a large urban primary care clinic and were included if their scores exceeded the 75th percentile on a brief screener of early behavior problems . Families were r and omly assigned to receive the home-based parenting intervention or st and ard pediatric primary care . The observed number of infant total ( i.e. , token ) and different ( i.e. , type ) utterances spoken during an observation of an infant-led play and a parent-report measure of infant externalizing behavior problems were examined at pre- and post-intervention and at 3- and 6-month follow-ups . Infants receiving the intervention demonstrated a significantly higher number of observed different and total utterances at the 6-month follow-up compared to infants in st and ard care . Furthermore , there was an indirect effect of the intervention on infant language production , such that the intervention led to decreases in infant externalizing behavior problems from pre- to post-intervention , which , in turn , led to increases in infant different utterances at the 3- and 6-month follow-ups and total utterances at the 6-month follow-up . Results provide initial evidence for the effect of this brief and home-based intervention on infant language production , including the indirect effect of the intervention on infant language through improvements in infant behavior , highlighting the importance of targeting behavior problems in early intervention Stepping Stones Triple P ( SSTP ) is a parenting program design ed for families of a child with a disability . The current study involved a r and omized controlled trial of Group Stepping Stones Triple P ( GSSTP ) for a mixed-disability group . Participants were 52 families of children diagnosed with an Autism Spectrum Disorder , Down syndrome , Cerebral Palsy , or an intellectual disability . The results demonstrated significant improvements in parent-reported child behavior , parenting styles , parental satisfaction , and conflict about parenting . Results among participants were similar despite children 's differing impairments . The intervention effect was maintained at 6-month follow-up . The results indicate that GSSTP is a promising intervention for a mixed-disability group . Limitations of the study , along with areas for future research , are also discussed Mothers of children r and omly allocated to an experimental group attended fortnightly group parental language training sessions , over a 6-month period . Mothers of children allocated to a matched no intervention control group received no special attention . The results showed significantly greater gains in the expressive language skills of the experimental group compared to the control group . A second experiment was design ed to compare the parental involvement approach with direct , individual treatment and to clarify the role of non-specific ' Hawthorne-type ' effects . The experimental group mothers attended parental language training sessions , as above . The parental control group mothers also attended training sessions , with the emphasis on general learning skills rather than language . A third group of children received individual , direct speech and language therapy . Results showed significantly greater language gains in the parental language training group and in the individual group in comparison with the non-specific training group . The two former groups did not differ significantly , indicating that , for these groups and this methodology , parental language training is as effective as individual speech and language therapy . The results also indicate that the effectiveness of the parental involvement approach can not be accounted for by non-specific factors . The research findings are discussed , together with the professional implication s of the study and recommendations for further research A r and omized controlled trial was used to evaluate a parent training intervention for caregivers with preschool-age children with developmental disabilities . The 21 families in the experimental group received usual care plus the 12-week Incredible Years Parent Training Program with developmental delay modifications . Families in the control group ( n = 23 ) received usual care , including early childhood education and related services . Results suggest that this parent training intervention was superior to usual care for young children with developmental delays or disabilities in reducing negative parent-child interactions and child behavior problems . Participants in the experimental group indicated high satisfaction with treatment . Additional research is necessary to document maintenance and generalization of treatment outcomes A media-based program for parents of mentally retarded children presented information on self-help skill teaching primarily through videotapes and instructional manuals . Sixty-one families were r and omly assigned to media-based training , the same curriculum with a professional leader , or a delayed-training control condition . Media-trained families evaluated their program very positively and showed significantly greater gains than did control parents on all but one outcome measure . Live training increased parents ' knowledge of behavioral principles more than did media-based training , but otherwise the results of the two conditions were quite similar . Media-based programs may be a cost-effective way to make parent training more widely available Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder . To investigate the underlying causal mechanisms , we conducted a r and omized clinical trial of an experimental intervention ( Focused Playtime Intervention , FPI ) that aims to enhance responsive parental communication ( N = 70 ) . Results showed a significant treatment effect of FPI on responsive parental behaviors . Findings also revealed a conditional effect of FPI on children ’s expressive language outcomes at 12-month follow up , suggesting that children with baseline language skills below 12 months ( n = 24 ) are most likely to benefit from FPI . Parents of children with more advanced language skills may require intervention strategies that go beyond FPI ’s focus on responsive communication Children with intellectual disability were r and omly assigned to receive Milieu Communication Teaching ( MCT ) at one 1-hr session per week ( low dose frequency , LDF ) or five 1-hr sessions per week ( high dose frequency , HDF ) over 9 months ( Fey , Yoder , Warren , & Bredin-Oja , 2013 . Non-Down syndrome ( NDS ) and Down syndrome ( DS ) subgroups were matched on intelligence , mental age , and chronological age . The NDS group had significantly more growth in spoken vocabulary than the DS group . In the DS subgroup , the HDF group had more spoken vocabulary growth than the LDF group when IQ was controlled . In both etiological subgroups , the HDF group yielded greater vocabulary production outcomes than the LDF group for children who played functionally with a range of objects PURPOSE To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching ( RE/PMT ) for children with developmental delay and RE/PMT 's effects on parenting stress in a r and omized clinical trial . METHOD Fifty-one children , age 24 - 33 months , with no more than 10 expressive words or signs , were r and omly assigned to treatment/no-treatment groups . Thirteen children in each group had a diagnosis of Down syndrome . RESULTS In 1 of 2 multivariate comparisons , the RE/PMT group exhibited superior gains in communication compared with the no-treatment group . The treatment effect for overall use of intentional communication acts in the child-examiner context was significant ( d = .68 , 95 % confidence interval = 0.12 - 1.24 ) . There were no effects on child outcomes due to presence or absence of Down syndrome . RE/PMT led to modest increases in recoding of child acts by parents of children who did not have Down syndrome . There were no effects on parenting stress associated with the intervention or the presence or absence of Down syndrome . CONCLUSIONS RE/PMT may be applied clinical ly with the expectation of medium-size effects on the child 's rate of intentional communication acts after 6 months of intervention . The approach warrants further investigation with modifications , such as delivery at higher intensity levels Because young children with disabilities are at elevated risk for development of challenging behaviors , and caregivers of these children typically lack access to evidence -based parenting interventions , two r and omized trials were conducted to examine the impact of an evidence -based parenting intervention , Stepping Stones Triple P ( SSTP ) , as a selective preventive intervention . Both studies targeted parents of children under two with a variety of disabilities who were enrolled in the IDEA Part C Early Intervention ( EI ) system in one state . SSTP was delivered in family homes . In Study One , 49 families were r and omly assigned to EI services as usual , with or without SSTP ; a 52 % attrition rate from treatment was seen . No significant between-group differences were seen aside from a trend toward reduced symptoms of parental depression at follow-up . Intervention group children demonstrated significant decline in behavior problems from post treatment to follow-up , and there was a trend toward improved parenting style in the intervention group during this same time frame . Study Two incorporated a separate workforce intervention for EI service coordinators ; 40 families on their caseloads were then r and omly assigned to receive EI services as usual with or without SSTP . Attrition from treatment was limited to 20 % . No differential impact was seen on child behavior ; a trend was noted post-treatment on parent symptoms of depression and on the observed parent-child relationship . At 12-month follow-up , there was a trend favoring improvement in the intervention group in parenting style ; statistically significant impact was also seen on the observed quality of the parent-child relationship . SSTP shows promise as a selective preventive intervention for an early intervention population . Reasons for the differential findings between the two studies are explored and suggestions for future research are provided PURPOSE The authors sought to determine whether a program of 5 weekly doses of milieu communication teaching ( MCT ) would yield improvements in children 's communication and word use compared with a once-weekly delivery of the same treatment . METHOD Sixty-four children with intellectual and communication delay were r and omly assigned to receive 60-min sessions of MCT either 1 time or 5 times per week over a 9-month treatment . Growth curves were fit to data collected at 5 points before , during , and after the MCT was delivered . RESULTS With groups collapsed , significant growth across the experimental period was observed on all measures , but this was not associated unconditionally with treatment intensity . Children who played with 9 or more objects during a st and ard play assessment , an empirically identified cut-point , benefited more from the high- than from the low-intensity treatment on lexical measures ( Hedges 's g range = .49 to .65 ) . CONCLUSIONS More MCT is not always better for all children . Clinicians can expect that increasing the frequency of MCT sessions will yield moderate enhancement of outcomes if the child has high interest in objects A series of instructional manuals in behavior modification with retarded children was tested as a self-contained re source and as part of three larger training programs involving different amounts of professional assistance to parents : telephone consultations , training groups , training groups plus home visits . One hundred and sixty families were r and omly assigned to the four training conditions or to a delayed-treatment control group . The 20-week treatment period emphasized the programming of self-help skills , but also provided an introduction to programming language skills and managing behavior problems . The manuals-alone format was as effective as the more expensive training formats in producing gains in children 's self-help skills and fostering knowledge of behavioral principles in mothers . The two group-training formats produced more efforts at behavior-problem management , greater gains in knowledge of principles by fathers , and higher self-confidence as teachers . Telephone consultation was generally the least effective training format ; the manuals-alone condition was surprisingly effective . Some implication s of the results for future strategies of family intervention were discussed A r and omized control study was conducted to evaluate Responsive Teaching ( RT ) with a sample of 15 Turkish preschool-aged children with Down syndrome ( DS ) and their mothers over a six-month period of time . RT is an early intervention curriculum that attempts to promote children 's development by encouraging parents to engage in highly responsive interactions with them . Subjects were r and omly assigned to treatment conditions : the control group consisted of st and ard preschool classroom services ; the RT group received bi-weekly RT parent-child sessions in addition to st and ard services . RT mothers made significantly greater increases in their Responsiveness and Affect as wellas decreases in Directiveness than control group mothers . There were also significant group differences in children 's interactive engagement and development . Children in the RT group improved their developmental quotient scores by an average of 47 % compared to 7 % for children in the control group . Results are described in terms of the effects of parental responsive interaction on the developmental functioning of children with DS |
2,311 | 27,557,486 | Minimally invasive cardiac surgery is as safe as conventional surgery and could reduce costs due to a shorter period spent in ICU | BACKGROUND Minimally invasive ( MI ) cardiac surgery was introduced to reduce problems associated with a full sternotomy .
This meta- analysis aim ed to investigate the effects of minimally invasive cardiac surgery on a range of clinical outcomes . | BACKGROUND Pulmonary dysfunction is still a major problem in coronary artery bypass grafting ( CABG ) . The purpose of this r and omized study was to determine the effect of different CABG techniques on pulmonary function . METHODS Fifty eight patients with severe obstructive pulmonary disease had elective isolated coronary surgery . The surgical methods for the patients with chronic obstructive pulmonary disease ( COPD ) were st and ard CABG in 18 patients ( group 1 ) , beating heart surgery in 19 patients ( group 2 ) , and minimally invasive direct coronary artery bypass grafting ( MIDCABG ) in 21 patients ( group 3 ) . RESULTS The earliest extubation time was from group 3 ( p < 0.001 ) . The average stay in the intensive care unit was significantly longer in group 1 ( 2.6 + /- 1.5 days ) than in groups 2 ( 1.4 + /- 0.8 days ) and 3 ( 1.1 + /- 0.8 days ) ( p < 0.05 ) . The most prevalent respiratory morbidity was atelectasis that developed in 6 patients from group 1 , in 2 patients from group 2 , and in 3 patients from group 3 . Forced expiratory volumes in 1 second ( FEV1 ) obtained in the second postoperative month were significantly lower than preoperative values only in group 1 ( p < 0.05 ) . Forced vital capacity ( FVC ) values were significantly lower than the preoperative values in all three groups ( p < 0.05 ) . CONCLUSIONS Off-pump bypass surgical procedures are more advantageous than on-pump methods for patients with COPD . These patients can be operated on using the beating heart technique or by using MIDCABG to prevent side effects of CPB on pulmonary function and effects of sternotomy OBJECTIVE The authors performed a retrospective cost analysis for patients undergoing revascularization of their left anterior descending ( LAD ) coronary artery either by st and ard coronary artery bypass grafting ( CABG ) , percutaneous transluminal coronary angioplasty ( PTCA ) , or minimally invasive coronary artery bypass grafting ( MICABG ) . SUMMARY BACKGROUND DATA Minimally invasive CABG has become a safe and effective alternative treatment for single-vessel coronary artery disease . However , the acceptance of this procedure as a routine alternative for the treatment of coronary artery disease will depend on both long-term graft patency rates as well as a competitive market cost . METHODS The authors conducted a retrospective analysis of three patient groups undergoing LAD coronary revascularization from January 1995 to July 1996 . Ten patients were selected r and omly from this period after PTCA of an LAD lesion with or without stenting . Nine patients underwent st and ard CABG on cardiopulmonary bypass with a left internal mammary artery . Nine patients received MICABG via a limited left anterior thoracotomy and left internal mammary artery to LAD grafting without the use of cardiopulmonary bypass . RESULTS Percutaneous transluminal coronary angioplasty ( n = 10 ) was unsuccessful in two patients . One patient in the MICABG group ( n = 9 ) was converted successfully to conventional CABG because of an intramyocardial LAD and dilated left ventricle . There was no operative morbidity or mortality in any group . Average length of stay postprocedure was decreased significantly for both the MICABG and PTCA groups when compared with that of conventional CABG ( n = 9 ) ( 2.7 + 0.26 , p = 0.009 , and 2.6 + 0.54 , p = 0.006 , vs. 4.8 + 0.46 , respectively ) . Total hospital costs for the MICABG and PTCA groups were significantly less when compared with those of st and ard CABG ( $ 10,129 + 1104 , p = 0.0028 , and $ 9113 + 3,039 , p = 0.0001 , vs. $ 17,816 + 1043 , respectively ) . There were no statistically significant differences between the MICABG and PTCA groups . CONCLUSIONS The final role of minimally invasive CABG is unclear . This procedure is clearly cost effective when compared with that of PTCA and conventional CABG . The long-term patency rates for MICABG will determine its overall efficacy OBJECTIVE In order to evaluate the traumatic effects of median sternotomy and cardiopulmonary bypass ( CPB ) in conventional and minimally invasive coronary artery bypass grafting , inflammatory response was studied in a prospect i ve r and omized trial in patients referred to single-vessel coronary artery bypass grafting . METHODS Four surgical techniques were compared : group 1 , median sternotomy with CPB in ten patients ( eight male , two female ; aged 59.6+/-11.0 years ( mean+/-SD ) ) ; group 2 , median sternotomy and off-pump in ten patients ( seven male , three female ; aged 65.1+/-10.0 years ) ; group 3 , minithoracotomy with CPB in ten patients ( seven male , three female , aged 61.2+/-10.4 years ) ; group 4 , minithoracotomy and off-pump in ten patients ( nine male , one female , aged 62.9+/-9.8 years ) . All patients received a left internal mammary artery graft to the left anterior descending artery ( LAD ) . Clinical data , perioperative values of cytokines and cardiac enzymes were monitored . RESULTS There were no major complications . Troponin-T and creatine kinase isoenzyme MB ( CK-MB ) levels were significantly higher in CPB procedures ( P<0.0056 ; multivariate general linear model ) . Interleukin-6 ( IL-6 ) levels were significantly higher in minithoracotomy procedures . Interleukin-1 ( IL-1 ) was significantly increased in all patients compared with the preoperative values . CONCLUSIONS The use of CPB is combined with higher levels of troponin-T and CK-MB as signs of myocardial damage . Surgical access was identified as a trigger of inflammatory response , as minithoracotomy is related to higher levels of IL-6 . IL-1 increased in all procedures and this occurred independently of the surgical access or the use of CPB , which points out a potential relationship between inflammatory response and anesthesia . Neither CPB nor surgical access influenced the clinical outcome in the treatment of coronary artery single-vessel bypass grafting BACKGROUND This study compares conventional coronary artery bypass grafting ( CABG ) with port access CABG via a left anterior small thoracotomy in patients requiring surgical multivessel revascularization . Clinical , neuropsychological , and angiographic outcomes were studied , as well as parameters of myocardial and cerebral protection . Pathogenicity of cardiopulmonary bypass ( CPB ) was further evaluated by measuring parameters of peripheral limb ischemia and inflammatory whole-body response . METHODS In a prospect i ve r and omized study , 40 patients who required multivessel CABG were assigned to either conventional CABG via complete median sternotomy ( group A ) or port access CABG via minithoracotomy ( group B ) . Control angiograms were performed in group B only . In addition , patients underwent neuropsychological testing after the operation . CK , CK-MB , and Troponin T levels were documented . S-100B protein and neuron-specific enolase ( NSE ) served to quantify cerebral injury . The terminal complement complex ( C5b-9 ) and myeloperoxidase concentrations were determined to analyze inflammatory whole-body response after CPB . RESULTS There was no mortality . One patient suffered a retro grade aortic dissection immediately after onset of CPB , but had an uneventful postoperative course after surgical repair . Troponin T and CK-MB showed no difference between groups . CK and myoglobin were significantly higher in the minimally invasive cohort . Changes in complement activation ( C5b-9 ) and myeloperoxidase during CPB markers of the whole-body inflammatory response were similar in both groups . S-100B concentrations in the port access group were significantly higher , whereas NSE levels were similar in both groups . Both groups did not display any significant difference in neuropsychological testing . CONCLUSIONS Minimally invasive multivessel CABG via minithoracotomy using port access technology is feasible and safe . Though prolonged operating and CPB times with significantly higher S-100B concentrations were observed in group B , equivalent myocardial and cerebral protection and similar whole-body inflammatory response were documented OBJECTIVE Minimally invasive coronary artery bypass grafting is safe and widely applicable , and may be associated with fewer transfusions and infections , and better recovery than st and ard coronary artery bypass grafting . However , graft patency rates remain unknown . The Minimally Invasive Coronary Artery Bypass Grafting Patency Study prospect ively evaluated angiographic graft patency 6 months after minimally invasive coronary artery bypass grafting . METHODS In this dual-center study , 91 patients were prospect ively enrolled to undergo minimally invasive coronary artery bypass grafting via a 4- to 7-cm left thoracotomy approach . The left internal thoracic artery , the ascending aorta for proximal anastomoses , and all coronary targets were directly accessed without endoscopic or robotic assistance . The study primary outcome was graft patency at 6 months , using 64-slice computed tomography angiography . Secondary outcomes included conversions to sternotomy and major adverse cardiovascular events ( Clinical Trial Registration Unique identifier : NCT01334866 ) . RESULTS The mean age of patients was 64 ± 8 years , the mean ejection fraction was 51 % ± 11 % , and there were 10 female patients ( 11 % ) in the study . Surgeries were performed entirely off-pump in 68 patients ( 76 % ) . Complete revascularization was achieved in all patients , and the median number of grafts was 3 . There was no perioperative mortality , no conversion to sternotomy , and 2 reopenings for bleeding . Transfusion occurred in 24 patients ( 26 % ) . The median length of hospital stay was 4 days , and all patients were followed to 6 months , with no mortality or major adverse cardiovascular events . Six-month computed tomography angiographic graft patency was 92 % for all grafts and 100 % for left internal thoracic artery grafts . CONCLUSIONS Minimally invasive coronary artery bypass grafting is safe , feasible , and associated with excellent outcomes and graft patency at 6 months post-surgery OBJECTIVE The results of mitral repair for complex Barlow valves are adequate and support earlier intervention . It is unknown whether these results are reproducible in the context of minimally invasive surgery via right minithoracotomy . METHODS We r and omized patients with Barlow mitral disease ( bileaflet prolapse ) to have conventional open repair via median sternotomy ( MS group ) or minimally invasive ( MI group ) repair . Repair was done using polytetrafluoroethylene chordal reimplantation for both leaflets . In the MI group , we adopted right minithoracotomy , peripheral cannulation , external aortic clamping , and surgery under direct vision . RESULTS Both groups comprised 70 patients . The operative and the cardiopulmonary bypass times were significantly longer in the MI group ( P = .003 and P = .012 ) . Mitral repair was successful in 98.5 % MI patients and 100 % MS patients . Operative mortality was comparable . The mean mechanical ventilation time , intensive care unit stay , and hospital stay were lower in the MI group ( P = .014 , P = .02 , and P = .03 , ) . Mean pain score was lower in the MI group at postoperative days 2 and 4 . At follow-up , the freedom from moderate ( 2 + ) or severe ( 3 + or 4 + ) mitral regurgitation was 98 % versus 97 % ( P = .9 ) . Two patients underwent reoperation ( 1 in each group ) for late failure of repair . The Kaplan-Meier analysis confirmed these results . CONCLUSIONS Our data indicate that the optimal st and ard-of-care results of mitral repair for complex disease ( Barlow ) are reproducible in the minimally invasive setting s through right minithoracotomy and direct vision . The minimally invasive technique can be proposed for complex mitral disease and early referral of these patients can be encouraged BACKGROUND AND AIM OF THE STUDY A prospect i ve r and omized study was performed to compare conventional with minimally invasive aortic valve replacement ( AVR ) . METHODS Forty consecutive patients scheduled for elective aortic valve surgery were prospect ively r and omized either to the conventional group ( group A , complete median sternotomy ) or minimally invasive group ( group B , partial upper sternotomy ) . Intraoperative and postoperative clinical data , and markers of myocardial and cerebral protection were determined . Neuropsychological tests were carried out to quantify psychological disorders . RESULTS Operative time and cardiopulmonary bypass time were slightly longer in group B , but not significantly so . No significant inter-group differences were found for postoperative pain scores and respiratory function . Chest tube drainage was significantly less in group B ( 495 + /- 165 versus 240 + /- 69 ml , p = 0.008 ) . Creatine kinase ( CK ) , CK-MB and troponin T levels were similar in both groups . Neither S-100B protein nor neuron-specific enolase levels differed significantly between groups at all sampling times . There were no strokes in the entire cohort . None of the neuropsychological tests yielded significant inter-group differences between conventional and minimally invasive surgery . CONCLUSION The safety and reliability of AVR via a partial upper sternotomy is reported . Minimally invasive AVR can be performed with only slightly longer operative times , good cosmetic results and significantly less blood loss . A limited surgical access affected neither the patients ' neurological outcome nor the efficacy of myocardial protection BACKGROUND Off-pump coronary surgery is an established method of less invasive cardiac surgery . We compared our early results in patents with I-vessel disease who underwent surgery with full sternotomy with off-pump coronary artery bypass ( OPCAB ) or a left anterior minithoracotomy with minimally invasive direct coronary artery bypass grafting ( MIDCAB ) without cardiopulmonary bypass . METHODS From July 2003 to June 2006 , 54 patients with single-vessel disease of the left anterior descending artery who underwent surgery performed by the same surgical team were included in this prospect i ve study . Of these patients , 27 underwent MIDCAB through an anterolateral minithoracotomy , and 27 had OPCAB through a full sternotomy . Patients were selected for the surgical groups on the basis of general condition , anatomical aspects , type of coronary lesions , comorbidities , and patient preferences . Demographic , operative , and postoperative data were collected prospect ively . RESULTS Demographic data , Canadian Cardiovascular Society Classification , and comorbidities were identical for both groups . There were no cases of operative mortality , early graft insufficiency , myocardial infa rct ion , cerebrovascular accident , or conversion to cardiopulmonary bypass in either group . Duration s of mechanical ventilation and total hospital stay were shorter in the MIDCAB group , 6.8+/-3.0 hours vs 8.3+/-1.6 hours and 4.5+/-0.7 days vs 5.2+/-1.4 days ( P= .03 and P= .03 ) , respectively . Atrial fibrillation was seen in 2 patients in each group ; all were returned to sinus rhythm by medical therapy . CONCLUSION Although MIDCAB grafting is a challenging technique , it may be safely performed on selected patients with low postoperative mortality and morbidity We compared the use of right infra-axillary minithoracotomy and conventional median sternotomy in direct open-heart surgery in 59 adults undergoing elective surgery for mitral valve stenosis , mitral valve disease , atrial septal defect repair , left atrial myxoma excision or mitral and tricuspid valve disease . Patients were r and omized to the infra-axillary minithoracotomy group ( Group A ; n = 29 ) or the median sternotomy group ( Group B ; n = 30 ) . Post-operative outcomes ( post-operative bleeding ; cross-clamp time ; length of hospital and intensive care unit stays ; and postoperative blood transfusion and analgesic requirements ) were recorded and compared ; they were found to be significantly lower in Group A than Group B. We concluded that right infra-axillary minithoracotomy is less invasive and can be used safely in adults as an alternative approach to conventional median sternotomy for some cardiac operations . Further multicentre studies in adults are now needed OBJECTIVE Our objective was to compare off-pump coronary artery bypass surgery carried out via a left anterolateral thoracotomy ( ThoraCAB ) or via a conventional median sternotomy ( OPCAB ) . BACKGROUND Recent advances in minimally invasive cardiac surgery have extended the technique to allow complete surgical revascularization on the beating heart via thoracotomy . METHODS Patients undergoing nonemergency primary surgery were enrolled between February 2007 and September 2009 at 2 centers . The primary outcome was the time from surgery to fitness for hospital discharge as defined by objective criteria . RESULTS A total of 93 patients were r and omized to off-pump coronary artery bypass surgery via a median sternotomy ( OPCAB ) and 91 to off-pump coronary artery bypass surgery via a left anterolateral thoracotomy ( ThoraCAB ) . The surgery was longer for patients in the ThoraCAB group ( median , 4.1 vs 3.3 hours ) and there were fewer with more than 3 grafts ( 2 % vs 17 % ) . The median time from surgery to fitness for discharge was 6 days ( interquartile range , 4 - 7 ) in the ThoraCAB group versus 5 days ( interquartile range , 4 - 7 ) in the OPCAB group ( P = .53 ) . The intubation time was shorter , by on average 65 minutes , in the ThoraCAB group ( P = .017 ) , although the time in intensive care was similar ( P = .91 ) . Pain scores were similar ( P = .97 ) , but more analgesia was required in the ThoraCAB group ( median duration , 38.8 vs 35.5 hours , P < .001 ; tramadol use , 66 % vs 49 % , P = .024 ) . ThoraCAB was associated with significantly worse lung function at discharge ( average difference , -0.25 L , P = .01 ) but quality of life scores at 3 and 12 months were similar ( P = .52 ) . The average total cost was 10 % higher with ThoraCAB ( P = .007 ) . CONCLUSIONS ThoraCAB result ed in no overall clinical benefit relative to OPCAB |
2,312 | 23,466,170 | Results for ORR , PFS , and /or OS in patients receiving pemetrexed in combination with other chemotherapeutic agents and /or radiotherapy were promising in the first-line treatment setting .
Pemetrexed was associated with acceptable grade 3 - 4 hematologic toxicities ; it did not result in nonhematologic toxicities commonly seen with cisplatin , such as nephrotoxicity , ototoxicity , and neuropathy .
Results of this review suggest that pemetrexed is an active chemotherapeutic in combination with other agents or radiotherapy in patients with HNC . | Pemetrexed has been evaluated as a novel chemotherapeutic for head and neck cancer ( HNC ) .
In this review , we examined the efficacy and tolerability of pemetrexed in patients with HNC . | BACKGROUND Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly BACKGROUND A r and omized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil ( TPF ) with cisplatin and fluorouracil ( PF ) , followed by chemoradiotherapy . METHODS We r and omly assigned 501 patients ( all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were c and i date s for organ preservation ) to receive either TPF or PF induction chemotherapy , followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week . The primary end point was overall survival . RESULTS With a minimum of 2 years of follow-up ( > or =3 years for 69 % of patients ) , significantly more patients survived in the TPF group than in the PF group ( hazard ratio for death , 0.70 ; P=0.006 ) . Estimates of overall survival at 3 years were 62 % in the TPF group and 48 % in the PF group ; the median overall survival was 71 months and 30 months , respectively ( P=0.006 ) . There was better locoregional control in the TPF group than in the PF group ( P=0.04 ) , but the incidence of distant metastases in the two groups did not differ significantly ( P=0.14 ) . Rates of neutropenia and febrile neutropenia were higher in the TPF group ; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group . CONCLUSIONS Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy . ( Clinical Trials.gov number , NCT00273546 [ Clinical Trials.gov ] . ) BACKGROUND We studied the combination of pemetrexed , a multi-targeted antifolate , and cetuximab , an mAb against the epidermal growth factor receptor , with radiotherapy in poor prognosis head and neck cancer . PATIENTS AND METHODS Patients received pemetrexed on days 1 , 22 , and 43 on a dose-escalation scheme with starting level ( 0 ) 350 mg/m(2 ) ( level -1 , 200 mg/m(2 ) ; level + 1 , 500 mg/m(2 ) ) with concurrent radiotherapy ( 2 Gy/day ) and cetuximab in two separate cohorts , not previously irradiated ( A ) and previously irradiated ( B ) , who received 70 and 60 - 66 Gy , respectively . Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated . RESULTS Thirty-two patients were enrolled . The maximum tolerated dose of pemetrexed was 500 mg/m(2 ) in cohort A and 350 mg/m(2 ) in cohort B. Prophylactic antibiotics were required . In cohort A , two dose-limiting toxicities ( DLTs ) occurred ( febrile neutropenia ) , one each at levels 0 and + 1 . In cohort B , two DLTs occurred at level + 1 ( febrile neutropenia ; death from perforated duodenal ulcer and sepsis ) . Grade 3 mucositis was common . No association of gene polymorphisms with toxicity or efficacy was evident . CONCLUSION The addition of pemetrexed 500 mg/m(2 ) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients Purpose This phase I study characterized the pharmacokinetics of free and total platinum derived from cisplatin administered alone and in combination with pemetrexed . Secondary objectives were to assess the pharmacokinetics of pemetrexed when it is combined with cisplatin as well as to evaluate the safety profile and document antitumor activity associated with this combination . Methods An open-label , two-arm , cross-over phase 1 study was performed in patients with squamous cell carcinoma of the head and neck , age ≥18 years , an Eastern Cooperative Oncology Group performance status of 0–2 , and adequate organ function . Blood sample s were taken and pharmacokinetics evaluated for the first two cycles using noncompartmental analysis . Patients received either pemetrexed ( 500 mg m−2 ) plus cisplatin ( 75 mg m−2 ) administered in cycle 1 followed by cisplatin alone in cycle 2 ; or in the reverse order ( i.e. , cisplatin alone in cycle 1 followed by pemetrexed plus cisplatin in cycle 2 ) . Each treatment cycle was 21 days and patients received folic acid , vitamin B12 supplementation , and dexamethasone prophylaxis . After the first two cycles , patients continued study treatment with pemetrexed plus cisplatin every 3 weeks up to a maximum of six total treatment cycles . Toxicities were grade d by the investigators according to the National Cancer Institute Common Toxicity Criteria for Adverse Events ( CTCAE ) , version 3.0 . Results A total of 13 patients were treated ; one patient was discontinued from the study after cycle 1 for failure to meet baseline eligibility criteria for renal function . The ratios and 90 % confidence intervals ( CI ) comparing the pharmacokinetics for cisplatin administered with pemetrexed to those for cisplatin administered alone for free platinum were : Cmax = 1.08 ( CI : 0.92 , 1.27 ) and AUC = 0.93 ( CI : 0.82 , 1.06 ) ; and , total platinum were : Cmax = 0.97 ( CI : 0.88 , 1.06 ) and AUC = 0.87 ( CI : 0.81 , 0.93 ) . These results indicate that platinum pharmacokinetics ( free and total ) are similar , whether cisplatin is administered alone or combined with pemetrexed . The pemetrexed pharmacokinetic results were consistent with those from previous single-agent pemetrexed studies and a previous study of pemetrexed in combination with cisplatin . The combination of pemetrexed and cisplatin did not show any unexpected toxicities . Consistent with the platinum pharmacokinetic results , co-administration with pemetrexed did not appear to enhance cisplatin-related toxicities . Of the 13 treated patients , 11 had stable disease as the best overall response and 2 had progressive disease . Conclusions The pharmacokinetics of free platinum derived from cisplatin were not altered by co-administration with pemetrexed , and in agreement with this , no unexpected cisplatin-induced toxicities were observed when these drugs were combined PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy . Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time BACKGROUND Concurrent chemoreirradiation therapy ( CRRT ) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck ( SCCHN ) . We hypothesized that response to induction chemotherapy ( IC ) would improve outcome and predict increased survival . PATIENTS AND METHODS Subjects with recurrent SCCHN not amenable to st and ard therapy were eligible . IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14 , followed by surgical resection , if appropriate , and /or CRRT consisting of carboplatin , pemetrexed , and single daily fractionated radiotherapy . RESULTS Thirty-five subjects were enrolled , 31 were assessable for response , with 11 responders [ response rate = 35 % ; 95 % confidence interval ( CI ) 19.2 - 54.6 ] . Among 24 subjects who started CRRT , 11 were assessable for radiographic response , 4 complete response , 2 partial response , and 5 progressive disease . Median progression-free survival and overall survival ( OS ) were 5.5 months ( 95 % CI 3.6 - 8.3 ) and 9.5 months ( 95 % CI 7.2 - 15.4 ) , respectively . One-year OS was 43 % ( 95 % CI 26 % to 58 % ) . Subjects who responded to IC had improved survival ( P = 0.02 ) . Toxic effects included mucositis , dermatitis , neutropenia , infection , hemorrhage , dehydration , and pain . CONCLUSIONS The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN . Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT Thymidylate synthase ( TS ) and p53 are central molecules in the regulation of cell growth . Differences in the intracellular expression of these proteins by tumor cells may have predictive value for response to chemotherapy and early failure in patients with squamous cell cancer of the head and neck ( SCCHN ) . Immunohistochemistry was used to assess the tumor cell expression of TS and p53 in pre-therapy biopsies from patients with advanced SCCHN treated with an induction chemotherapy protocol , PFL . Sample s were available from 11 of 16 nonresponders , 13 of 19 early failures with progression within 24 months of treatment , and a r and om selection of 13 from 45 long-term , disease-free survivors ( LTS ) . High TS expression was seen in the majority of sample s from all three groups , 67 % versus 78 % versus 93 % , respectively ; however , only one of seven ( 14 % ) sample s with low TS was from a LTS patient . TS expression did not differ in patients by sex , age , site of primary tumor , differentiation or stage . p53 was expressed in 33 % of patient sample s and did not predict response or correlate with sex , age , site of primary tumor , differentiation , or stage . Small primary tumors with extensive nodal disease were less likely to express p53 than larger primary tumors with or without nodal involvement . The data suggest that TS and p53 content have a limited prognostic value in patients treated with PFL , although tumors with lower TS expression appeared to be less likely to respond . Differences between this study and other investigations of TS and p53 may be disease site- and regimen-specific . Statistically significant differences between response groups may emerge from larger , site-specific , protocol -driven studies of TS and p53 BACKGROUND Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer ( NSCLC ) histology . We further review ed the differential efficacy of pemetrexed according to histology in two large , phase III NSCLC trials . METHODS One study tested pemetrexed versus docetaxel in previously treated patients ( n = 571 ) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients ( n = 1,725 ) with advanced NSCLC . Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions ( THIs ) for overall survival ( OS ) and progression-free survival ( PFS ) . For each histologic subgroup , the Kaplan-Meier method was used to estimate unadjusted within-arm medians , and Cox models were used to estimate covariate-adjusted between-arm hazard ratios ( HRs ) . RESULTS In both studies , treatment arms were well balanced for histology . THIs were statistically significant ( p < .005 ) for both OS and PFS . Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators ( HR , 0.78 and 0.84 , respectively ) , whereas squamous patients had shorter survival ( HR , 1.56 and 1.23 , respectively ) . Whereas the efficacy of pemetrexed regimens differed according to histology , it did not differ for docetaxel or for cisplatin plus gemcitabine . Pemetrexed was well tolerated across histologic groups . CONCLUSIONS The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology . These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma , but , because of efficacy and safety advantages , pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC PURPOSE To up date a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer . METHODS An up date committee review ed literature published since the last guideline up date in 2002 . RESULTS Thirty-nine reports met the inclusion criteria : palifermin and dexrazoxane , three reports ( two studies ) each ; amifostine , 33 reports ( 31 studies ) ; and mesna , no published r and omized trials identified since 2002 . RECOMMENDATIONS Dexrazoxane is not recommended for routine use in breast cancer ( BC ) in adjuvant setting , or metastatic setting with initial doxorubicin-based chemotherapy . Consider use with metastatic BC and other malignancies , for patients who have received more than 300 mg/m(2 ) doxorubicin who may benefit from continued doxorubicin-containing therapy . Cardiac monitoring should continue in patients receiving doxorubicin . Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity , reduction of grade 3 to 4 neutropenia ( alternative strategies are reasonable ) , and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer . It is not recommended for protection against thrombocytopenia , prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy , prevention of radiation therapy-associated mucositis in head and neck cancer , or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer . Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation ( SCT ) for hematologic malignancies with total-body irradiation ( TBI ) conditioning regimens , and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens . Data are insufficient to recommend use in the non-SCT setting BACKGROUND Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck . We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . METHODS We r and omly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin ( at a dose of 100 mg per square meter of body-surface area on day 1 ) or carboplatin ( at an area under the curve of 5 mg per milliliter per minute , as a 1-hour intravenous infusion on day 1 ) plus fluorouracil ( at a dose of 1000 mg per square meter per day for 4 days ) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab ( at a dose of 400 mg per square meter initially , as a 2-hour intravenous infusion , then 250 mg per square meter , as a 1-hour intravenous infusion per week ) for a maximum of 6 cycles . Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects , whichever occurred first . RESULTS Adding cetuximab to platinum-based chemotherapy with fluorouracil ( platinum-fluorouracil ) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab ( hazard ratio for death , 0.80 ; 95 % confidence interval , 0.64 to 0.99 ; P=0.04 ) . The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months ( hazard ratio for progression , 0.54 ; P<0.001 ) and increased the response rate from 20 % to 36 % ( P<0.001 ) . The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia ( 19 % and 13 % , respectively ) , neutropenia ( 23 % and 22 % ) , and thrombocytopenia ( 11 % in both groups ) . Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group ( P=0.02 ) . Of 219 patients receiving cetuximab , 9 % had grade 3 skin reactions and 3 % had grade 3 or 4 infusion-related reactions . There were no cetuximab-related deaths . CONCLUSIONS As compared with platinum-based chemotherapy plus fluorouracil alone , cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . ( Clinical Trials.gov number , NCT00122460 . OBJECTIVES We examined the prognostic factors ( clinical , demographic , and health-related quality of life [ HRQoL ] ) of overall survival ( OS ) and progression-free survival ( PFS ) in patients with recurrent/metastatic head and neck cancer ( HNC ) who were treated with pemetrexed plus cisplatin versus cisplatin in a phase III , multinational , r and omized trial . MATERIAL S AND METHODS Five subscales of the Functional Assessment of Cancer Therapy-Head and Neck Cancer ( FACT-H&N ) , modified to score from 0 to 100 , measured HRQoL at baseline and during treatment . Univariate and multivariate Cox proportional hazards models were used on data pooled from both treatment arms to assess the effect of baseline prognostic factors on OS and PFS . RESULTS Of 795 patients r and omized , 704 completed a baseline FACT-H&N and were included in the analysis . Age ( < 65 versus ⩾65 ; HR=0.74 , 95 % CI : 0.61 - 0.90 ) , race ( Caucasian versus non-Caucasian ; HR=0.83 , 95 % CI : 0.70 - 0.98 per table ) , Eastern Cooperative Oncology Group performance status ( ECOG PS ; 0/1 versus 2 ; HR=0.44 , 95 % CI : 0.35 - 0.56 ) , prior surgery/radiotherapy in the last 6months ( no versus yes ; HR=0.74 , 95 % CI : 0.61 - 0.90 ) , and primary site of disease ( oral cavity versus other ; HR=1.37 , 95 % CI : 1.15 - 1.63 ) were significantly prognostic of OS in univariate models , as were baseline scores on four FACT-H&N subscales ( physical well-being , emotional well-being , functional well-being , additional concerns-H&N ; HRs=0.82 - 0.94 ; all P⩽0.002 ) . In multivariate models , significant prognostic factors were age ( HR=0.78 ) ; race ( HR=0.76 per table ) ; ECOG PS ( HR=0.56 ) ; prior surgery/radiotherapy ( HR=0.76 ) ; and baseline scores of the FACT-H&N subscales of physical well-being , social/family well-being , and additional concerns-H&N ( HRs=0.89 - 0.94 ; all P⩽0.014 per table ) . CONCLUSIONS The results suggest that baseline HRQoL scores are prognostic indicators of OS in recurrent/metastatic HNC in addition to other known clinical and demographic indicators . HRQoL might be considered as a stratification factor in r and omized clinical trials of recurrent/metastatic HNC PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P < .001 ) , febrile neutropenia ( 12.7 % v 1.9 % ; P < .001 ) , neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P < .001 ) , hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P < .001 ) and all grade alopecia ( 37.7 % v 6.4 % ; P < .001 ) compared with patients receiving pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type This phase 2 trial evaluated the tolerability and clinical efficacy of the combination of oxaliplatin and pemetrexed as an induction chemotherapy regimen in locally advanced head and neck squamous cell carcinoma ( HNSCC ) |
2,313 | 25,058,694 | Anti-VEGF mAbs did not significantly increase overall mortality , cardiovascular mortality , stroke , myocardial infa rct ion , VTEs , or hypertension . | IMPORTANCE Few data exist regarding the systemic safety of intravitreal antivascular endothelial growth factor ( anti-VEGF ) monoclonal antibody ( mAb ) .
OBJECTIVE To conduct a systematic review and meta- analysis to evaluate the risk of major cardiovascular and nonocular hemorrhagic events in patients with neovascular age-related macular degeneration ( AMD ) , diabetes mellitus-associated macular edema ( DME ) , or retinal vein occlusions ( RVOs ) who receive intravitreal anti-VEGF mAbs . | PURPOSE The role of vascular endothelial growth factor ( VEGF ) in diabetic macular edema ( DME ) was tested with ranibizumab , a specific antagonist of VEGF . DESIGN A nonr and omized clinical trial . METHODS Ten patients with chronic DME received intraocular injections of 0.5 mg of ranibizumab at baseline and at one , two , four , and six months . The primary outcome was change in foveal thickness between baseline and seven months , and the secondary outcome measures were changes from baseline in visual acuity and macular volume . RESULTS Mean values at baseline were 503 microm for foveal thickness , 9.22 mm3 for macular volume , and 28.1 letters ( 20/80 ) read on an Early Treatment Diabetic Retinopathy Study ( ETDRS ) visual acuity chart . At seven months ( one month after the fifth injection ) , the mean foveal thickness was 257 microm , which was a reduction of 246 microm ( 85 % of the excess foveal thickness present at baseline ; P = .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance ) . The macular volume was 7.47 mm3 , which was a reduction of 1.75 mm3 ( 77 % of the excess macular volume at baseline ; P = .009 ) . Mean visual acuity was 40.4 letters ( 20/40 ) , which was an improvement of 12.3 letters ( P = .005 ) . The injections were well-tolerated with no ocular or systemic adverse events . CONCLUSION Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME , which demonstrated that VEGF is an important therapeutic target for DME . A r and omized , controlled , double-masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME Purpose To report 1-year visual and anatomic outcomes of a prospect i ve , double-masked r and omised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration ( AMD ) . Methods Patients who met inclusion criteria were r and omised 2 : 1 to bevacizumab or ranibizumab . All subjects and investigators ( except for the pharmacist responsible for study assignments ) were masked to treatment arms . Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart . Patients were given either bevacizumab or ranibizumab every month for the first 3 months , followed by an optical coherence tomography-guided , variable-dosing treatment schedule . Main outcomes measured included visual acuity , foveal thickness , and total number of injections over the 1-year treatment period . Results In total , 15 patients received bevacizumab and 7 patients received ranibizumab . The average pre-operative visual acuity was 34.9 letters in the bevacizumab group , and 32.7 letters in the ranibizumab group . At 1-year follow-up , mean vision was 42.5 letters in the bevacizumab group , and 39.0 letters in the ranibizumab group . Two-tailed t-test failed to showed statistical significance between the two groups ( P=0.5 ) . Patients in the bevacizumab group underwent an average of eight injections , whereas patients in the ranibizumab group underwent a mean of four injections ( P=0.001 ) . Conclusion The 1-year outcomes of a prospect i ve , double-masked , r and omised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD . Total injections given over the treatment period were significantly different between the two groups . Further studies with larger sample sizes are warranted OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment . DESIGN Multicenter , r and omized clinical trial . PARTICIPANTS Patients ( n = 1107 ) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial . INTERVENTIONS At enrollment , patients were assigned to 4 treatment groups defined by drug ( ranibizumab or bevacizumab ) and dosing regimen ( monthly or as needed ) . At 1 year , patients initially assigned to monthly treatment were reassigned r and omly to monthly or as-needed treatment , without changing the drug assignment . MAIN OUTCOME MEASURES Mean change in visual acuity . RESULTS Among patients following the same regimen for 2 years , mean gain in visual acuity was similar for both drugs ( bevacizumab-ranibizumab difference , -1.4 letters ; 95 % confidence interval [ CI ] , -3.7 to 0.8 ; P = 0.21 ) . Mean gain was greater for monthly than for as-needed treatment ( difference , -2.4 letters ; 95 % CI , -4.8 to -0.1 ; P = 0.046 ) . The proportion without fluid ranged from 13.9 % in the bevacizumab-as-needed group to 45.5 % in the ranibizumab monthly group ( drug , P = 0.0003 ; regimen , P < 0.0001 ) . Switching from monthly to as-needed treatment result ed in greater mean decrease in vision during year 2 ( -2.2 letters ; P = 0.03 ) and a lower proportion without fluid ( -19 % ; P < 0.0001 ) . Rates of death and arteriothrombotic events were similar for both drugs ( P > 0.60 ) . The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab ( 39.9 % vs. 31.7 % ; adjusted risk ratio , 1.30 ; 95 % CI , 1.07 - 1.57 ; P = 0.009 ) . Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor ( VEGF ) . CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period . Treatment as needed result ed in less gain in visual acuity , whether instituted at enrollment or after 1 year of monthly treatment . There were no differences between drugs in rates of death or arteriothrombotic events . The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF PURPOSE To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab ( ivB ) and modified Early Treatment of Diabetic Retinopathy Study ( ETDRS ) macular laser therapy ( MLT ) in patients with persistent clinical ly significant diabetic macular edema ( CSME ) . DESIGN Prospect i ve , r and omized , masked , single-center , 2-year , 2-arm clinical trial . PARTICIPANTS A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT . METHODS Subjects were r and omized to either ivB ( 6 weekly ; minimum of 3 injections and maximum of 9 injections in the first 12 months ) or MLT ( 4 monthly ; minimum of 1 treatment and maximum of 4 treatments in the first 12 months ) . MAIN OUTCOME MEASURES The primary end point was the difference in ETDRS best-corrected visual acuity ( BCVA ) at 12 months between the bevacizumab and laser arms . RESULTS The baseline mean ETDRS BCVA was 55.7+/-9.7 ( range 34 - 69 ) in the bevacizumab group and 54.6+/-8.6 ( range 36 - 68 ) in the laser arm . The mean ETDRS BCVA at 12 months was 61.3+/-10.4 ( range 34 - 79 ) in the bevacizumab group and 50.0+/-16.6 ( range 8 - 76 ) in the laser arm ( P = 0.0006 ) . Furthermore , the bevacizumab group gained a median of 8 ETDRS letters , whereas the laser group lost a median of 0.5 ETDRS letters ( P = 0.0002 ) . The odds of gaining > or = 10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group ( adjusted odds ratio , 5.1 ; 95 % confidence interval , 1.3 - 19.7 ; P = 0.019 ) . At 12 months , central macular thickness decreased from 507+/-145 microm ( range 281 - 900 microm ) at baseline to 378+/-134 microm ( range 167 - 699 microm ) ( P<0.001 ) in the ivB group , whereas it decreased to a lesser extent in the laser group , from 481+/-121 microm ( range 279 - 844 microm ) to 413+/-135 microm ( range 170 - 708 microm ) ( P = 0.02 ) . The median number of injections was 9 ( interquartile range [ IQR ] 8 - 9 ) in the ivB group , and the median number of laser treatments was 3 ( IQR 2 - 4 ) in the MLT group . CONCLUSIONS The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia OBJECTIVES To compare ranibizumab with focal/grid laser or a combination of both in diabetic macular edema ( DME ) . DESIGN Prospect i ve , r and omized , interventional , multicenter clinical trial . PARTICIPANTS A total of 126 patients with DME . METHODS Subjects were r and omized 1:1:1 to receive 0.5 mg of ranibizumab at baseline and months 1 , 3 , and 5 ( group 1 , 42 patients ) , focal/grid laser photocoagulation at baseline and month 3 if needed ( group 2 , 42 patients ) , or a combination of 0.5 mg of ranibizumab and focal/grid laser at baseline and month 3 ( group 3 , 42 patients ) . MAIN OUTCOME MEASURES The primary end point was the change from baseline in best-corrected visual acuity ( BCVA ) at month 6 . RESULTS At month 6 , the mean gain in BCVA was significantly greater in group 1 ( + 7.24 letters , P = 0.01 , analysis of variance ) compared with group 2 ( -0.43 letters ) , and group 3 ( + 3.80 letters ) was not statistically different from groups 1 or 2 . For patients with data available at 6 months , improvement of 3 lines or more occurred in 8 of 37 ( 22 % ) in group 1 compared with 0 of 38 ( 0 % ) in group 2 ( P = 0.002 , Fisher exact test ) and 3 of 40 ( 8 % ) in group 3 . Excess foveal thickness was reduced by 50 % , 33 % , and 45 % in groups 1 , 2 , and 3 , respectively . CONCLUSIONS During a span of 6 months , ranibizumab injections by the current protocol had a significantly better visual outcome than focal/grid laser treatment in patients with DME PURPOSE To evaluate the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( AMD ) . DESIGN Phase IIIb , multicenter , r and omized , double-masked , sham injection-controlled trial in patients with predominantly or minimally classic or occult with no classic CNV lesions . METHODS Patients were r and omized 1:1:1 to 0.3 mg ranibizumab ( n = 60 ) , 0.5 mg ranibizumab ( n = 61 ) , or sham ( n = 63 ) treatment groups . The primary efficacy endpoint was mean change from baseline visual acuity ( VA ) at month 12 . RESULTS Mean changes from baseline VA at 12 months were -16.3 , -1.6 , and -0.2 letters for the sham , 0.3 mg , and 0.5 mg groups , respectively ( P < or = .0001 , each ranibizumab dose vs sham ) . Ranibizumab arrested CNV growth and reduced leakage from CNV . However , the treatment effect declined in the ranibizumab groups during quarterly dosing ( e.g. , at three months the mean changes from baseline VA had been gains of 2.9 and 4.3 letters for the 0.3 mg and 0.5 mg doses , respectively ) . Results of subgroups analyses of mean change from baseline VA at 12 months by baseline age , VA , and lesion characteristics were consistent with the overall results . Few serious ocular or nonocular adverse events occurred in any group . CONCLUSIONS Ranibizumab administered monthly for three months and then quarterly provided significant VA benefit to patients with AMD-related subfoveal CNV and was well tolerated . The incidence of serious ocular or nonocular adverse events was low OBJECTIVE The 2-year , phase III trial design ated Anti-vascular endothelial growth factor ( VEGF ) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization ( CNV ) in Age-related Macular Degeneration ( ANCHOR ) compared ranibizumab with verteporfin photodynamic therapy ( PDT ) in treating predominantly classic CNV . DESIGN Multicenter , international , r and omized , double-masked , active-treatment-controlled clinical trial . PARTICIPANTS Patients with predominantly classic , subfoveal CNV not previously treated with PDT or antiangiogenic drugs . INTERVENTION Patients were r and omized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab ( 0.3 mg or 0.5 mg ) injection . The need for PDT ( active or sham ) retreatment was evaluated every 3 months using fluorescein angiography ( FA ) . MAIN OUTCOME MEASURES The primary , intent-to-treat efficacy analysis was at 12 months , with continued measurements to month 24 . Key measures included the percentage losing < 15 letters from baseline visual acuity ( VA ) score ( month 12 primary efficacy outcome measure ) , percentage gaining > or=15 letters from baseline , and mean change over time in VA score and FA-assessed lesion characteristics . Adverse events were monitored . RESULTS Of 423 patients ( 143 PDT , 140 each in the 2 ranibizumab groups ) , the majority ( > or=77 % in each group ) completed the 2-year study . Consistent with results at month 12 , at month 24 the VA benefit from ranibizumab was statistically significant ( P<0.0001 vs. PDT ) and clinical ly meaningful : 89.9 % to 90.0 % of ranibizumab-treated patients had lost < 15 letters from baseline ( vs. 65.7 % of PDT patients ) ; 34 % to 41.0 % had gained > or=15 letters ( vs. 6.3 % of PDT group ) ; and , on average , VA was improved from baseline by 8.1 to 10.7 letters ( vs. a mean decline of 9.8 letters in PDT group ) . Changes in lesion anatomic characteristics on FA also favored ranibizumab ( all comparisons P<0.0001 vs. PDT ) . Overall , there was no imbalance among groups in rates of serious ocular and nonocular adverse events . In the pooled ranibizumab groups , 3 of 277 ( 1.1 % ) patients developed presumed endophthalmitis in the study eye ( rate per injection = 3/5921 [ 0.05 % ] ) . CONCLUSIONS In this 2-year study , ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset , predominantly classic CNV . Rates of serious adverse events were low . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references Objectives To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration . Design Prospect i ve , double masked , multicentre , r and omised controlled trial . Setting Three ophthalmology centres in the United Kingdom . Participants 131 patients ( mean age 81 ) with wet age related macular degeneration r and omised 1:1 to intervention or control . Interventions Intravitreous bevacizumab ( 1.25 mg , three loading injections at six week intervals followed by further treatment if required at six week intervals ) or st and ard treatment available at the start of the trial ( photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration , or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration ) . Main outcome measures Primary outcome : proportion of patients gaining ≥15 letters of visual acuity at one year ( 54 weeks ) . Secondary outcomes : proportion of patients with stable vision and mean change in visual acuity . Results Of the 131 patients enrolled in the trial , five patients did not complete the study because of adverse events , loss to follow-up , or death . In the bevacizumab group , 21 ( 32 % ) patients gained 15 or more letters from baseline visual acuity compared with two ( 3 % ) in the st and ard care group ( P<0.001 ) ; the estimated adjusted odds ratio was 18.1 ( 95 % confidence interval 3.6 to 91.2 ) and the number needed to treat was 4 ( 3 to 6 ) . In addition , the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment ( 91 % ( 59 ) v 67 % ( 44 ) in st and ard care group ; P<0.001 ) . Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the st and ard care group ( P<0.001 ) , and the initial improvement at week 18 ( plus 6.6 letters ) was sustained to week 54 . Among 65 patients treated with bevacizumab , there were no cases of endophthalmitis or serious uveitis related to the intervention . All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over st and ard care . Conclusions Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to st and ard care ( pegaptanib sodium , verteporfin , sham ) , with low rates of serious ocular adverse events . Treatment improved visual acuity on average at 54 weeks . Trial registration number Current controlled trials IS RCT Aims To determine the level of vascular endothelial growth factor ( VEGF ) in the plasma of patients with diabetic macular edema ( DME ) and of patients with exudative age-related macular degeneration ( ARMD ) before and after intravitreal injection of bevacizumab , ranibizumab or pegaptanib . Methods 30 patients with DME and 30 patients with ARMD were included in this r and omized controlled study . Patients were r and omized to treatment with ranibizumab ( 0.5 mg ) , bevacizumab ( 1.25 mg ) or pegaptanib ( 0.3 mg ) . 10 patients with DME received bevacizumab , 10 ranibizumab and 10 pegaptanib . The same r and omized treatment allocation applied to the 30 patients with ARMD . The concentrations of VEGF were measured by ELISA just before the injection , after 7 days and 1 month . Results Plasma VEGF in patients with exudative ARMD before the injection of bevacizumab was 89.7 pg/ml . It was significantly reduced to 25.1 pg/ml after 7 days ( p=0.01 ) , and to 22.8 pg/ml after 1 month ( p=0.008 ) . In patients with DME the same systemic reduction by bevacizumab was observed with a significant decrease of baseline VEGF level from 72.2 pg/ml to 13.7 pg/ml after 7 days ( p=0.008 ) and 17.1 pg/ml at 4 weeks with ( p=0.012 ) . No significant reductions of plasma VEGF levels were observed in patients receiving ranibizumab or pegaptanib during follow-up . Conclusions Bevacizumab significantly reduces the level of VEGF in the blood plasma for up to one month in patients with DME as well as in those with ARMD . No significant systemic effects of intravitreal ranibizumab or pegaptanib on plasma VEGF could be observed PURPOSE To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema ( DME ) patients . DESIGN Two parallel , method ologically identical , phase III , multicenter , double-masked , sham injection-controlled , r and omized studies . PARTICIPANTS Adults with vision loss from DME ( best-corrected visual acuity [ BCVA ] , 20/40 - 20/320 Snellen equivalent ) and central subfield thickness ≥275 μm on time-domain optical coherence tomography ( OCT ) . INTERVENTION Monthly intravitreal ranibizumab ( 0.5 or 0.3 mg ) or sham injections . Macular laser was available per- protocol -specified criteria . MAIN OUTCOME MEASURES Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months . RESULTS In RISE ( NCT00473330 ) , 377 patients were r and omized ( 127 to sham , 125 to 0.3 mg , 125 to 0.5 mg ) . At 24 months , 18.1 % of sham patients gained ≥15 letters versus 44.8 % of 0.3-mg ( P<0.0001 ; difference vs sham adjusted for r and omization stratification factors , 24.3 % ; 95 % confidence interval [ CI ] , 13.8 - 34.8 ) and 39.2 % of 0.5-mg ranibizumab patients ( P<0.001 ; adjusted difference , 20.9 % ; 95 % CI , 10.7 - 31.1 ) . In RIDE ( NCT00473382 ) , 382 patients were r and omized ( 130 to sham , 125 to 0.3 mg , 127 to 0.5 mg ) . Significantly more ranibizumab-treated patients gained ≥15 letters : 12.3 % of sham patients versus 33.6 % of 0.3-mg patients ( P<0.0001 ; adjusted difference , 20.8 % ; 95 % CI , 11.4 - 30.2 ) and 45.7 % of 0.5-mg ranibizumab patients ( P<0.0001 ; adjusted difference , 33.3 % ; 95 % CI , 23.8 - 42.8 ) . Significant improvements in macular edema were noted on OCT , and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients . Ranibizumab-treated patients underwent significantly fewer macular laser procedures ( mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3 - 0.8 in ranibizumab groups ) . Ocular safety was consistent with prior ranibizumab studies ; endophthalmitis occurred in 4 ranibizumab patients . The total incidence of deaths from vascular or unknown causes , nonfatal myocardial infa rct ions , and nonfatal cerebrovascular accidents , which are possible effects from systemic vascular endothelial growth factor inhibition , was 4.9 % to 5.5 % of sham patients and 2.4 % to 8.8 % of ranibizumab patients . CONCLUSIONS Ranibizumab rapidly and sustainably improved vision , reduced the risk of further vision loss , and improved macular edema in patients with DME , with low rates of ocular and nonocular harm PURPOSE Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion ( BRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter trial . PARTICIPANTS A total of 397 patients with macular edema after BRVO . METHODS Eligible patients were r and omized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections . After 6 months , all patients with study eye best-corrected visual acuity ( BCVA ) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab . Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met . MAIN OUTCOME MEASURES The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12 . Additional visual and anatomic parameters were assessed . RESULTS Mean ( 95 % confidence interval ) change from baseline BCVA letter score at month 12 was 16.4 ( 14.5 - 18.4 ) and 18.3 ( 15.8 - 20.9 ) in the 0.3 mg and 0.5 mg groups , respectively , and 12.1 ( 9.6 - 14.6 ) in the sham/0.5 mg group ( P<0.01 , each ranibizumab group vs. sham/0.5 mg ) . The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0 % and 60.3 % in the 0.3 mg and 0.5 mg groups , respectively , and 43.9 % in the sham/0.5 mg group . On average , there was a marked reduction in central foveal thickness ( CFT ) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group , which was sustained through month 12 . No new ocular or nonocular safety events were identified . CONCLUSIONS At month 12 , treatment with ranibizumab as needed during months 6 - 11 maintained , on average , the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO , with low rates of ocular and nonocular safety events . In the sham/0.5 mg group , treatment with ranibizumab as needed for 6 months result ed in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA , but not to the extent of that in the 2 ranibizumab groups . Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references OBJECTIVE The expression of vascular endothelial growth factor ( VEGF ) is elevated in diabetic macular edema ( DME ) . Ranibizumab binds to and inhibits multiple VEGF variants . We investigated the safety and efficacy of ranibizumab in DME involving the foveal center . RESEARCH DESIGN AND METHODS This was a 12-month , multicenter , sham-controlled , double-masked study with eyes ( age > 18 years , type 1 or 2 diabetes , central retinal thickness [ CRT ] ≥300 μm , and best corrected visual acuity [ BCVA ] of 73–39 ETDRS letters [ Early Treatment Diabetic Retinopathy Study ] ) r and omly assigned to intravitreal ranibizumab ( 0.3 or 0.5 mg ; n = 51 each ) or sham ( n = 49 ) . The treatment schedule comprised three monthly injections , after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation ( protocol -defined criteria ) . After month 1 , dose-doubling was permitted ( protocol -defined criteria , injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter ) . Efficacy ( BCVA and CRT ) and safety were compared between pooled ranibizumab and sham arms using the full analysis set ( n = 151 , patients receiving ≥1 injection ) . RESULTS At month 12 , mean ± SD BCVA improved from baseline by 10.3 ± 9.1 letters with ranibizumab and declined by 1.4 ± 14.2 letters with sham ( P < 0.0001 ) . Mean CRT reduction was 194.2 ± 135.1 μm with ranibizumab and 48.4 ± 153.4 μm with sham ( P < 0.0001 ) . Gain of ≥10 letters BCVA from baseline occurred in 60.8 % of ranibizumab and 18.4 % of sham eyes ( P < 0.0001 ) . Safety data were consistent with previous studies of intravitreal ranibizumab . CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME . Future clinical trials are required to confirm its long-term efficacy and safety PURPOSE To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion ( BRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS A total of 397 patients with macular edema following BRVO . METHODS Eligible patients were r and omized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections . MAIN OUTCOME MEASURES The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 6 . Secondary outcomes included other parameters of visual function and central foveal thickness ( CFT ) . RESULTS Mean ( 95 % confidence interval [ CI ] ) change from baseline BCVA letter score at month 6 was 16.6 ( 14.7 - 18.5 ) and 18.3 ( 16.0 - 20.6 ) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 ( 5.1 - 9.5 ) in the sham group ( P<0.0001 for each ranibizumab group vs sham ) . The percentage of patients who gained > or = 15 letters in BCVA at month 6 was 55.2 % ( 0.3 mg ) and 61.1 % ( 0.5 mg ) in the ranibizumab groups and 28.8 % in the sham group ( P<0.0001 for each ranibizumab group vs sham ) . At month 6 , significantly more ranibizumab-treated patients ( 0.3 mg , 67.9 % ; 0.5 mg , 64.9 % ) had BCVA of > or = 20/40 compared with sham patients ( 41.7 % ; P<0.0001 for each ranibizumab group vs sham ) ; and CFT had decreased by a mean of 337 microm ( 0.3 mg ) and 345 microm ( 0.5 mg ) in the ranibizumab groups and 158 microm in the sham group ( P<0.0001 for each ranibizumab group vs sham ) . The median percent reduction in excess foveal thickness at month 6 was 97.0 % and 97.6 % in 0.3 mg and 0.5 mg groups and 27.9 % in the sham group . More patients in the sham group ( 54.5 % ) received rescue grid laser compared with the 0.3 mg ( 18.7 % ) and 0.5 mg ( 19.8 % ) ranibizumab groups . The safety profile was consistent with previous phase III ranibizumab trials , and no new safety events were identified in patients with BRVO . CONCLUSIONS Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid , effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events OBJECTIVE To investigate the safety and efficacy of intravitreal ranibizumab treatment combined with verteporfin photodynamic therapy ( PDT ) in patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration . METHODS In this 2-year , phase I/II , multicenter , r and omized , single-masked , controlled study , patients received monthly ranibizumab ( 0.5 mg ) ( n = 106 ) or sham ( n = 56 ) injections . The PDT was performed 7 days before initial ranibizumab or sham treatment and then quarterly as needed . MAIN OUTCOMES MEASURES Proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months ( primary efficacy outcome ) and the incidence and severity of adverse events . RESULTS At 12 months , 90.5 % of the ranibizumab-treated patients and 67.9 % of the control patients had lost fewer than 15 letters ( P<.001 ) . The most frequent ranibizumab-associated serious ocular adverse events were intraocular inflammation ( 11.4 % ) and endophthalmitis ( 1.9 % ; 4.8 % if including presumed cases ) . On average , patients with serious inflammation had better visual acuity outcomes at 12 months than did controls . Key serious nonocular adverse events included myocardial infa rct ions in the PDT-alone group ( 3.6 % ) and cerebrovascular accidents in the ranibizumab-treated group ( 3.8 % ) . CONCLUSION /APPLICATION TO CLINICAL PRACTICE : Ranibizumab + PDT was more efficacious than PDT alone for treating neovascular age-related macular degeneration . Although ranibizumab treatment increased the risk of serious intraocular inflammation , affected patients , on average , still experienced visual acuity benefit OBJECTIVE To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration ( AMD ) . DESIGN Twelve-month r and omized ( cohort 1 ) or open-label ( cohort 2 ) multicenter clinical trial . PARTICIPANTS A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization ( CNV ) secondary to AMD . METHODS Cohort 1 subjects were r and omized 1:1 to receive 0.3 mg ( n = 1169 ) or 0.5 mg ( n = 1209 ) intravitreal ranibizumab for 3 monthly loading doses . Dose groups were stratified by AMD treatment history ( treatment-naïve vs. previously treated ) . Cohort 1 subjects were retreated on the basis of optical coherence tomography ( OCT ) or visual acuity ( VA ) criteria . Cohort 2 subjects ( n = 1922 ) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion . Safety was evaluated at all visits . MAIN OUTCOME MEASURES Safety outcomes included the incidence of ocular and nonocular adverse events ( AEs ) and serious adverse events ( SAEs ) . Efficacy outcomes included changes in best-corrected VA over time . RESULTS Some 81.7 % of cohort 1 subjects and 49.9 % of cohort 2 subjects completed the 12-month study . The average total number of ranibizumab injections was 4.9 for cohort 1 and 3.6 for cohort 2 . The incidence of vascular and nonvascular deaths during the 12-month study was 0.9 % and 0.7 % in the cohort 1 0.3 mg group , 0.8 % and 1.5 % in the cohort 1 0.5 mg group , and 0.7 % and 0.9 % in cohort 2 , respectively . The incidence of death due to unknown cause was 0.1 % in both cohort 1 dose groups and cohort 2 . The number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups . Stroke rates were 0.7 % , 1.2 % , and 0.6 % in the 0.3 mg and 0.5 mg groups and cohort 2 , respectively . At month 12 , cohort 1 treatment-naïve subjects had gained an average of 0.5 ( 0.3 mg ) and 2.3 ( 0.5 mg ) VA letters and previously treated subjects had gained 1.7 ( 0.3 mg ) and 2.3 ( 0.5 mg ) VA letters . CONCLUSIONS Intravitreal ranibizumab was safe and well tolerated in a large population of subjects with neovascular AMD . Ranibizumab had a beneficial effect on VA . Future investigations will seek to establish optimal dosing regimens for persons with neovascular AMD . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references PURPOSE To compare the results of intravitreal bevacizumab ( IVB ) injection alone or in combination with intravitreal triamcinolone acetonide ( IVT ) versus macular laser photocoagulation ( MPC ) as a primary treatment of diabetic macular edema ( DME ) . DESIGN R and omized 3-arm clinical trial . PARTICIPANTS A total of 150 eyes of 129 patients with clinical ly significant DME and no previous treatment . METHODS The eyes were r and omly assigned to 1 of the 3 study arms : the IVB group , patients who received 1.25 mg IVB ( 50 eyes ) ; the IVB/IVT group , patients who received 1.25 mg of IVB and 2 mg of IVT ( 50 eyes ) ; and the MPC group , patients who underwent focal or modified grid laser ( 50 eyes ) . Retreatment was performed at 12-week intervals whenever indicated . MAIN OUTCOME MEASURES Change in best-corrected visual acuity ( VA ) at week 24 . RESULTS VA changes among the groups were statistically significant at 6 ( P<0.001 ) and 24 ( P = 0.012 ) weeks . The significant treatment effect was demonstrated in the IVB group at all follow-up visits and in the IVB/IVT group at 6 and 12 weeks . VA changes + /- st and ard deviation at 36 weeks were -0.28+/-0.25 , -0.04+/-0.33 , and + 0.01+/-0.27 logarithm of minimum angle of resolution in the IVB , IVB/IVT , and MPC groups , respectively ( P = 0.053 ) . Significant central macular thickness ( CMT ) reduction was observed in all groups only up to 6 weeks ; however , CMT changes were not significant among the groups in all visits . Overall , retreatment was required for 27 eyes up to 36 weeks ( 14 in the IVB group , 10 in the IVB/IVT group , and 3 in the MPC group ) . In the IVB group , in which a greater VA improvement was observed , only 1 injection was required in 72 % of the cases . VA improvement > 2 Snellen lines at 36 weeks was detected in 37 % , 25 % , and 14.8 % of patients in the IVB , IVB/IVT , and MPC groups , respectively . CONCLUSIONS Intravitreal bevacizumab injection in patients with DME yielded a better visual outcome at 24 weeks compared with macular photocoagulation . A change in CMT beyond the 6-week time point that corresponded to the vision change was not detected . No adjunctive effect of IVT was demonstrated . FINANCIAL DISCLOSURE(S ) The author(s ) have no proprietary or commercial interest in any material s discussed in this article Aim The current accepted st and ard treatment for neovascular age-related macular degeneration ( AMD ) consists of antivascular endothelial growth factor agents including ranibizumab and bevacizumab . The aim of the study was to examine whether bevacizumab is inferior to ranibizumab with respect to maintaining/improving visual acuity . Methods In this prospect i ve r and omised parallel group multicentre trial patients aged more than 50 years with treatment naive nAMD were included at 10 Austrian centres . Patients were r and omised to treatment either with 0.5 mg ranibizumab or 1.25 mg bevacizumab . Both groups received three initial monthly injections and thereafter monthly evaluation of visual acuity and the activity of the lesion . Re-treatment was scheduled as needed . Outcome measures were early treatment of diabetic retinopathy visual acuity , retinal thickness , lesion size and safety evaluation . Results A total of 321 patients were recruited of which four had to be excluded due to different reasons . Of the 317 remaining patients 154 were r and omised into the bevacizumab group and 163 into the ranibizumab group . At month 12 , there was a mean increase of early treatment of diabetic retinopathy visual acuity of 4.9 letters in the bevacizumab and 4.1 letters in the ranibizumab group ( p=0.78 ) . Furthermore , there were no significant differences in the decrease of retinal thickness , change of lesion size and number of adverse events between the groups . Conclusions Bevacizumab was equivalent to ranibizumab for visual acuity at all time points over 1 year . There was no significant difference of decrease of retinal thickness or number of adverse events BACKGROUND Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration ( AMD ) . In addition , bevacizumab is used off-label to treat AMD , despite the absence of similar supporting data . METHODS In a multicenter , single-blind , noninferiority trial , we r and omly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation . The primary outcome was the mean change in visual acuity at 1 year , with a noninferiority limit of 5 letters on the eye chart . RESULTS Bevacizumab administered monthly was equivalent to ranibizumab administered monthly , with 8.0 and 8.5 letters gained , respectively . Bevacizumab administered as needed was equivalent to ranibizumab as needed , with 5.9 and 6.8 letters gained , respectively . Ranibizumab as needed was equivalent to monthly ranibizumab , although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive . The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group ( 196 μm ) than in the other groups ( 152 to 168 μm , P=0.03 by analysis of variance ) . Rates of death , myocardial infa rct ion , and stroke were similar for patients receiving either bevacizumab or ranibizumab ( P>0.20 ) . The proportion of patients with serious systemic adverse events ( primarily hospitalizations ) was higher with bevacizumab than with ranibizumab ( 24.1 % vs. 19.0 % ; risk ratio , 1.29 ; 95 % confidence interval , 1.01 to 1.66 ) , with excess events broadly distributed in disease categories not identified in previous studies as areas of concern . CONCLUSIONS At 1 year , bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule . Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly . Differences in rates of serious adverse events require further study . ( Funded by the National Eye Institute ; Clinical Trials.gov number , NCT00593450 . ) Background / Aims : To compare retrospectively the incidence of arterial thromboembolic events ( ATEs ) in patients treated with bevacizumab or ranibizumab for exudative age-related macular degeneration . Methods : Charts of 378 patients treated with at least 1 intravitreal injection of ranibizumab or bevacizumab were review ed to calculate the incidence of ATEs . Only patients under monotherapy were analyzed . Results : ATEs occurred in 15 patients : 12 ( 12/97 ) with bevacizumab ( 12.4 % ) and 3 ( 3/219 ) with ranibizumab ( 1.4 % ) – odds ratio 10.16 ; 95 % confidence interval 2.80–36.93 ; p < 0.0001 . ATEs in the bevacizumab and ranibizumab cohorts included stroke , myocardial infa rct ion , angina pectoris , peripheral thromboembolic disease , transient ischemic attack , sudden death and lethal stroke . Conclusion : In this series , bevacizumab raised the risk of ATEs when compared to ranibizumab . In an elderly population with multiple cardiovascular risk factors , the new ATEs may not be attributed exclusively to the intravitreal bevacizumab administration . These findings raise an issue that must be confirmed in r and omized clinical trials PURPOSE To evaluate efficacy and safety of quarterly ( and then monthly ) ranibizumab during the 2-year Phase IIIb , multicenter , r and omized , double-masked , sham injection-controlled study of the efficacy and safety of ranibizumab in subjects with subfoveal CNV with or without classic CNV secondary to AMD ( PIER ) study . DESIGN Phase IIIb , multicenter , r and omized , double-masked , sham injection-controlled trial in patients with choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( AMD ) . METHODS Patients were r and omized 1:1:1 to sham injection ( n = 63 ) or 0.3 mg ( n = 60 ) or 0.5 mg ( n = 61 ) intravitreal ranibizumab monthly for 3 months and then quarterly . During study year 2 , eligible sham-group patients crossed over to 0.5 mg ranibizumab quarterly . Later in year 2 , all eligible r and omized patients rolled over to 0.5 mg ranibizumab monthly . Key efficacy and safety outcomes of the 2-year trial are reported . RESULTS At month 24 , visual acuity ( VA ) had decreased an average of 21.4 , 2.2 , and 2.3 letters from baseline in the sham , 0.3 mg , and 0.5 mg groups ( P < .0001 for each ranibizumab group vs sham ) . VA of sham patients who crossed over ( and subsequently rolled over ) to ranibizumab decreased across time , with an average loss of 3.5 letters 10 months after crossover . VA of 0.3 mg and 0.5 mg group patients who rolled over to monthly ranibizumab increased for an average gain of 2.2 and 4.1 letters , respectively , 4 months after rollover . The ocular safety profile of ranibizumab was favorable and consistent with previous reports . CONCLUSIONS Ranibizumab provided significant VA benefit in patients with AMD-related CNV compared with sham injection . Ranibizumab appeared to provide additional VA benefit to treated patients who rolled over to monthly dosing , but not to patients who began receiving ranibizumab after > 14 months of sham injections PURPOSE To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration ( nAMD ) . DESIGN Multicenter , noninferiority factorial trial with equal allocation to groups . The noninferiority limit was 3.5 letters . This trial is registered ( IS RCT N92166560 ) . PARTICIPANTS People > 50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart . METHODS We r and omized participants to 4 groups : ranibizumab or bevacizumab , given either every month ( continuous ) or as needed ( discontinuous ) , with monthly review . MAIN OUTCOME MEASURES The primary outcome is at 2 years ; this paper reports a prespecified interim analysis at 1 year . The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure . Other outcome measures are health-related quality of life , contrast sensitivity , near visual acuity , reading index , lesion morphology , serum vascular endothelial growth factor ( VEGF ) levels , and costs . RESULTS Between March 27 , 2008 and October 15 , 2010 , we r and omized and treated 610 participants . One year after r and omization , the comparison between bevacizumab and ranibizumab was inconclusive ( bevacizumab minus ranibizumab -1.99 letters , 95 % confidence interval [ CI ] , -4.04 to 0.06 ) . Discontinuous treatment was equivalent to continuous treatment ( discontinuous minus continuous -0.35 letters ; 95 % CI , -2.40 to 1.70 ) . Foveal total thickness did not differ by drug , but was 9 % less with continuous treatment ( geometric mean ratio [ GMR ] , 0.91 ; 95 % CI , 0.86 to 0.97 ; P = 0.005 ) . Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure ( odds ratio [ OR ] , 0.23 ; 95 % CI , 0.05 to 1.07 ; P = 0.03 ) . There was no difference between drugs in the proportion experiencing a serious systemic adverse event ( OR , 1.35 ; 95 % CI , 0.80 to 2.27 ; P = 0.25 ) . Serum VEGF was lower with bevacizumab ( GMR , 0.47 ; 95 % CI , 0.41 to 0.54 ; P<0.0001 ) and higher with discontinuous treatment ( GMR , 1.23 ; 95 % CI , 1.07 to 1.42 ; P = 0.004 ) . Continuous and discontinuous treatment costs were £ 9656 and £ 6398 per patient per year for ranibizumab and £ 1654 and £ 1509 for bevacizumab ; bevacizumab was less costly for both treatment regimens ( P<0.0001 ) . CONCLUSIONS The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive . Visual acuities with continuous and discontinuous treatment were equivalent . Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosures may be found after the references OBJECTIVE To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity ( BCVA ) over 12 months in diabetic macular edema ( DME ) . DESIGN A 12-month , r and omized , double-masked , multicenter , laser-controlled phase III study . PARTICIPANTS We included 345 patients aged ≥18 years , with type 1 or 2 diabetes mellitus and visual impairment due to DME . METHODS Patients were r and omized to ranibizumab + sham laser ( n = 116 ) , ranibizumab + laser ( n = 118 ) , or sham injections + laser ( n = 111 ) . Ranibizumab/sham was given for 3 months then pro re nata ( PRN ) ; laser/sham laser was given at baseline then PRN ( patients had scheduled monthly visits ) . MAIN OUTCOME MEASURES Mean average change in BCVA from baseline to month 1 through 12 and safety . RESULTS Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 ( + 6.1 and + 5.9 vs + 0.8 ; both P<0.0001 ) . At month 12 , a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level > 73 ( 20/40 Snellen equivalent ) with ranibizumab ( 22.6 % and 53 % , respectively ) and ranibizumab + laser ( 22.9 % and 44.9 % ) versus laser ( 8.2 % and 23.6 % ) . The mean central retinal thickness was significantly reduced from baseline with ranibizumab ( -118.7 μm ) and ranibizumab + laser ( -128.3 μm ) versus laser ( -61.3 μm ; both P<0.001 ) . Health-related quality of life , assessed through National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) , improved significantly from baseline with ranibizumab alone and combined with laser ( P<0.05 for composite score and vision-related subscales ) versus laser . Patients received ∼7 ( mean ) ranibizumab/sham injections over 12 months . No endophthalmitis cases occurred . Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms . Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study . CONCLUSIONS Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over st and ard laser in patients with visual impairment due to DME . Visual acuity gains were associated with significant gains in VFQ-25 scores . At 1 year , no differences were detected between the ranibizumab and ranibizumab + laser arms . Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration OBJECTIVE To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( AMD ) . DESIGN A 12-month , multicenter , r and omized , double-masked , active-controlled , phase IIIb study . PARTICIPANTS Patients with primary or recurrent subfoveal CNV secondary to AMD ( 353 patients ) , with predominantly classic , minimally classic , or occult ( no classic component ) lesions . INTERVENTION Patients were r and omized ( 1:1:1 ) to 0.3 mg quarterly , 0.5 mg quarterly , or 0.3 mg monthly doses of ranibizumab . Treatment comprised of a loading phase ( 3 consecutive monthly injections ) followed by a 9-month maintenance phase ( either monthly or quarterly injection ) . MAIN OUTCOME MEASURES Mean change in best-corrected visual acuity ( BCVA ) and central retinal thickness ( CRT ) from baseline to month 12 and the incidence of adverse events ( AEs ) . RESULTS In the per- protocol population ( 293 patients ) , BCVA , measured by Early Treatment Diabetic Retinopathy Study -like charts , increased from baseline to month 12 by 4.9 , 3.8 , and 8.3 letters in the 0.3 mg quarterly ( 104 patients ) , 0.5 mg quarterly ( 88 patients ) , and 0.3 mg monthly ( 101 patients ) dosing groups , respectively . Similar results were observed in the intent-to-treat ( ITT ) population ( 353 patients ) . The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 μm in 0.3 mg quarterly , -105.6 μm in 0.5 mg quarterly , and -105.3 μm in 0.3 mg monthly group . The most frequent ocular AEs were conjunctival hemorrhage ( 17.6 % , pooled quarterly groups ; 10.4 % , monthly group ) and eye pain ( 15.1 % , pooled quarterly groups ; 20.9 % , monthly group ) . There were 9 ocular serious AEs and 3 deaths ; 1 death was suspected to be study related ( cerebral hemorrhage ; 0.5 mg quarterly group ) . The incidences of key arteriothromboembolic events were low . CONCLUSIONS After 3 initial monthly ranibizumab injections , both monthly ( 0.3 mg ) and quarterly ( 0.3 mg/0.5 mg ) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD . At month 12 , BCVA gain in the monthly regimen was higher than that of the quarterly regimens . The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters . The safety profile was similar to that reported in prior ranibizumab studies PURPOSE To assess the efficacy and adverse-events profile of combined treatment with ranibizumab and verteporfin photodynamic therapy ( PDT ) in patients with predominantly classic choroidal neovascularization ( CNV ) secondary to neovascular age-related macular degeneration . DESIGN Two-year , multicenter , r and omized , single-masked , controlled study . METHODS Patients received monthly intravitreal injections of ranibizumab 0.5 mg ( n = 106 ) or sham injections ( n = 56 ) . All patients received PDT on day zero , then quarterly as needed . Efficacy assessment included changes in visual acuity ( VA ) and lesion characteristics and PDT frequency . Adverse events were summarized by incidence and severity . RESULTS At month 24 , 88 % of ranibizumab + PDT patients had lost < 15 letters from baseline VA ( vs 75 % for PDT alone ) , 25 % had gained > or=15 letters ( vs 7 % for PDT alone ) , and the two treatment arms differed by 12.4 letters in mean VA change ( P < .05 for all between-group differences ) . The VA benefit of adding ranibizumab to PDT in year one persisted through year two . On average , ranibizumab + PDT patients exhibited less lesion growth and greater reduction of CNV leakage and subretinal fluid accumulation , and required fewer PDT retreatments , than PDT-alone patients ( mean = 0.4 vs 3.0 PDT retreatments ) . Endophthalmitis and serious intraocular inflammation occurred , respectively , in 2.9 % and 12.4 % of ranibizumab + PDT patients and 0 % of PDT-alone patients . Incidences of serious nonocular adverse events were similar in the two treatment groups . CONCLUSIONS Through two years , ranibizumab + PDT was more effective than PDT alone and had a low rate of associated adverse events Purpose : To analyze cerebrovascular accidents ( CVAs ) pooled from large , r and omized , controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration . Methods : Events in five trials ( FOCUS , MARINA , ANCHOR , PIER , and SAILOR ) were analyzed using a st and ard safety monitoring process . Exact methods , stratified by study , were used to test for treatment differences based on odds ratios . A stepwise logistic regression model was fit to classify subjects ' risk for CVA based on medical history . Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods . Results : Pooled 2-year CVA rates were < 3 % ; odds ratios ( 95 % confidence intervals ) for CVA risk were 1.2 ( 0.4–4.4 ) for ranibizumab 0.3-mg versus control , 2.2 ( 0.8–7.1 ) for 0.5 mg versus control , and 1.5 ( 0.8–3.0 ) for 0.5-mg versus 0.3-mg ranibizumab . No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials . In pooled analyses , the difference between 0.5-mg ranibizumab and control was larger ( 7.7 [ 1.2–177 ] ) among high-risk CVA patients . Conclusion : This analysis provided some evidence , although not definitive , of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab . Continued monitoring for CVA within clinical trials seems warrented Purpose : To evaluate 14-week effects of intravitreal ranibizumab or triamcinolone in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation . Methods : Three hundred and forty-five eyes with a visual acuity of 20/320 or better , center-involved diabetic macular edema receiving focal/grid laser , and diabetic retinopathy receiving prompt panretinal photocoagulation were r and omly assigned to sham ( n = 123 ) , 0.5-mg ranibizumab ( n = 113 ) at baseline and 4 weeks , and 4-mg triamcinolone at baseline and sham at 4 weeks ( n = 109 ) . Treatment was at investigator discretion from 14 weeks to 56 weeks . Results : Mean changes ( ±SD ) in visual acuity letter score from baseline were significantly better in the ranibizumab ( + 1 ± 11 ; P < 0.001 ) and triamcinolone ( + 2 ± 11 ; P < 0.001 ) groups compared with those in the sham group ( −4 ± 14 ) at the 14-week visit , mirroring retinal thickening results . These differences were not maintained when study participants were followed for 56 weeks for safety outcomes . One eye ( 0.9 % ; 95 % confidence interval , 0.02%-4.7 % ) developed endophthalmitis after receiving ranibizumab . Cerebrovascular/cardiovascular events occurred in 4 % , 7 % , and 3 % of the sham , ranibizumab , and triamcinolone groups , respectively . Conclusion : The addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks . Whether continued long-term intravitreal treatment is beneficial can not be determined from this study Purpose : To evaluate the efficacy and safety of intravitreal ranibizumab for subfoveal choroidal neovascularization ( CNV ) secondary to age‐related macular degeneration ( AMD ) in Japanese patients PURPOSE To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion ( CRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS A total of 392 patients with macular edema after CRVO . METHODS Eligible patients were r and omized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections . MAIN OUTCOME MEASURES The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 6 . Secondary outcomes included other parameters of visual function and central foveal thickness ( CFT ) . RESULTS Mean ( 95 % confidence interval [ CI ] ) change from baseline BCVA letter score at month 6 was 12.7 ( 9.9 - 15.4 ) and 14.9 ( 12.6 - 17.2 ) in the 0.3 mg and 0.5 mg ranibizumab groups , respectively , and 0.8 ( -2.0 to 3.6 ) in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . The percentage of patients who gained > or = 15 letters in BCVA at month 6 was 46.2 % ( 0.3 mg ) and 47.7 % ( 0.5 mg ) in the ranibizumab groups and 16.9 % in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . At month 6 , significantly more ranibizumab-treated patients ( 0.3 mg = 43.9 % ; 0.5 mg = 46.9 % ) had BCVA of > or = 20/40 compared with sham patients ( 20.8 % ; P<0.0001 for each ranibizumab group vs. sham ) , and CFT had decreased by a mean of 434 microm ( 0.3 mg ) and 452 microm ( 0.5 mg ) in the ranibizumab groups and 168 microm in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . The median percent reduction in excess foveal thickness at month 6 was 94.0 % and 97.3 % in the 0.3 mg and 0.5 mg groups , respectively , and 23.9 % in the sham group . The safety profile was consistent with previous phase III ranibizumab trials , and no new safety events were identified in patients with CRVO . CONCLUSIONS Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO , with low rates of ocular and nonocular safety events |
2,314 | 21,831,318 | For homeless people with mental illness , provision of housing upon hospital discharge was effective in improving sustained housing .
For homeless people with substance abuse issues or concurrent disorders , provision of housing was associated with decreased substance use , relapses from periods of substance abstinence , and health services utilization , and increased housing tenure .
Abstinent dependent housing was more effective in supporting housing status , substance abstinence , and improved psychiatric outcomes than non-abstinence dependent housing or no housing .
Provision of housing also improved health outcomes among homeless population s with HIV .
Health promotion programs can decrease risk behaviours among homeless population s. Conclusions These studies provide important new evidence regarding interventions to improve health , housing status , and access to healthcare for homeless population s. The additional studies included in this current review provide further support for earlier evidence which found that coordinated treatment programs for homeless persons with concurrent mental illness and substance misuse issues usually result in better health and access to healthcare than usual care .
This review also provides a synthesis of existing evidence regarding interventions that specifically support homeless population s with HIV | Background Research on interventions to positively impact health and housing status of people who are homeless has received substantially increased attention over the past 5 years .
This rapid review examines recent evidence regarding interventions that have been shown to improve the health of homeless people , with particular focus on the effect of these interventions on housing status . | We illustrate Fairweather 's approach to Experimental Social Innovation and Dissemination with two experimental studies of programs to reduce homelessness for 168 and 225 people with mental illness and often substance abuse . Literally homeless participants were r and omly assigned to programs that emphasized consumer choice or to the usual continuum of care , in which housing and services are contingent on sobriety and progress in treatment . A drop-in center that eliminated barriers to access to services was more successful than control programs in reducing homelessness , but after 24 months only 38 % of participants had moved to community housing . A subsequent apartment program , in which individuals in the experimental condition moved to subsidized apartments directly from the street , with services under their control , had 79 % in stable housing ( compared to 27 % in the control group ) at the end of 6 months . Groups in this study did not differ on substance abuse or psychosocial outcomes Investigators examined the 6-month impact of three cognitive-behavioral HIV risk-reduction programs on behavioral factors ( substance use and sexual risk behaviors ) and cognitive and psychological re sources of 325 women who resided in emergency or sober-living shelters and their 308 intimate sexual partners . Participants were r and omized by shelter to a peer-mentored , a nurse case-managed , or a st and ard care HIV risk-reduction program . Significant improvements were observed in all groups in all behavioral factors and cognitive and psychological re sources except for self-esteem . Participants in the peer-mentored and nurse case-managed groups did not differ significantly from the st and ard group in self-esteem , life satisfaction , psychological well-being , use of noninjection drugs , sex with multiple partners , and unprotected sex at 6 months ( n = 633 ) . It was concluded that a st and ard approach by health care professionals appears to effectively modify HIV risk behaviors for a majority of homeless participants and may have important economic and policy implication s. Further , the impact of short-term programs that address psychological vulnerabilities of impoverished population s needs to be studied further PURPOSE This exploratory study examined the feasibility of homeless parents ' participation in an intervention to increase use of facilitating language strategies during interactions with their preschool children while residing in family homeless shelters . This study also examined the intervention 's impact on the parents ' use of facilitating language strategies , regardless of parent performance on a single-word receptive vocabulary test . METHOD Using a prospect i ve , pretest/posttest comparison group design , 12 parents were r and omly assigned to a 4-session experimental group training emphasizing use of facilitating language utterances with children following vocabulary testing . Four parents were r and omly assigned to a control group intervention . RESULTS It was feasible for parents to participate in the intervention . Before the intervention , individual experimental group parents with poor test performance demonstrated relatively high use of facilitating language utterances . After the intervention , the experimental group increased use of facilitating language utterances during interactions with their children . CONCLUSIONS This exploratory study provides initial evidence that it is feasible for parents to participate in , and benefit from , a brief language -based group intervention while residing in family homeless shelters . Further study of language -based interventions for these at-risk families and of the possible impact of parent language functioning on intervention benefit is needed A women 's therapeutic community ( TC ) design ed to prevent homelessness was evaluated using a quasi-experimental process . Propensity analysis selected comparable experimental ( E ) and comparison ( C ) participants . Significant improvements were found for the E group at the domain level , both in “ psychological ” dysfunction on symptoms ( e.g. , depression ) , and in “ health , ” including ratings of health and adherence to medication regimens . No significant difference was found at the domain level for “ parenting ” or “ housing stabilization , ” but specific outcomes did differ . For example , a greater number of children resided with the E group mothers who also assumed financial responsibility for more of their children OBJECTIVES This study tested a psychiatric rehabilitation approach for organizing and delivering services to street-dwelling persons with severe mental illness . METHODS Street-dwelling persons with severe mental illness were r and omly assigned to the experimental program ( called Choices ) or to st and ard treatment in New York City . We assessed study participants at baseline and at 6-month intervals over 24 months , using measures of service use , quality of life , health , mental health , and social psychological status . The average deviation from baseline summary statistic was employed to assess change . RESULTS Compared with persons in st and ard treatment ( n = 77 ) , members of the experimental group ( n = 91 ) were more likely to attend a day program ( 53 % vs 27 % ) , had less difficulty in meeting their basic needs , spent less time on the streets ( 55 % vs 28 % reduction ) , and spent more time in community housing ( 21 % vs 9 % increase ) . They showed greater improvement in life satisfaction and experienced a greater reduction in psychiatric symptoms . CONCLUSIONS With an appropriate service model , it is possible to engage disaffiliated population s , exp and their use of human services , and improve their housing conditions , quality of life , and mental health status Housing First is an effective intervention that ends and prevents homelessness for individuals with severe mental illness and co-occurring addictions . By providing permanent , independent housing without prerequisites for sobriety and treatment , and by offering support services through consumer-driven Assertive Community Treatment teams , Housing First removes some of the major obstacles to obtaining and maintaining housing for consumers who are chronically homeless . In this study , consumers diagnosed with severe mental illness and who had the longest histories of shelter use in a suburban county were r and omly assigned to either one of two Housing First programs or to a treatment-as-usual control group . Participants assigned to Housing First were placed in permanent housing at higher rates than the treatment-as-usual group and , over the course of four years , the majority of consumers placed by both Housing First agencies were able to maintain permanent , independent housing . Results also highlight that providers new to Housing First must be aware of ways in which their practice s may deviate from the essential features of Housing First , particularly with respect to enrolling eligible consumers on a first-come , first-served basis and separating clinical issues from tenant or housing responsibilities . Finally , other aspects of successfully implementing a Housing First program are discussed BACKGROUND Supported housing , integrating clinical and housing services , is a widely advocated intervention for homeless people with mental illness . In 1992 , the US Department of Housing and Urban Development ( HUD ) and the US Department of Veterans Affairs ( VA ) established the HUD-VA Supported Housing ( HUD-VASH ) program . METHODS Homeless veterans with psychiatric and /or substance abuse disorders or both ( N = 460 ) were r and omly assigned to 1 of 3 groups : ( 1 ) HUD-VASH , with Section 8 vouchers ( rent subsidies ) and intensive case management ( n = 182 ) ; ( 2 ) case management only , without special access to Section 8 vouchers ( n = 90 ) ; and ( 3 ) st and ard VA care ( n = 188 ) Primary outcomes were days housed and days homeless . Secondary outcomes were mental health status , community adjustment , and costs from 4 perspectives . RESULTS During a 3-year follow-up , HUD-VASH veterans had 16 % more days housed than the case management-only group and 25 % more days housed than the st and ard care group ( P<.001 for both ) . The case management-only group had only 7 % more days housed than the st and ard care group ( P = .29 ) . The HUD-VASH group also experienced 35 % and 36 % fewer days homeless than each of the control groups ( P<.005 for both ) . There were no significant differences on any measures of psychiatric or substance abuse status or community adjustment , although HUD-VASH clients had larger social networks . From the societal perspective , HUD-VASH was 6200 US dollars ( 15 % ) more costly than st and ard care . Incremental cost-effectiveness ratios suggest that HUD-VASH cost 45 US dollars more than st and ard care for each additional day housed ( 95 % confidence interval , -19 US dollars to 108 US dollars ) . CONCLUSIONS Supported housing for homeless people with mental illness results in superior housing outcomes than intensive case management alone or st and ard care and modestly increases societal costs Homelessness and unstable housing have been associated with HIV risk behavior and poorer health among persons living with HIV/AIDS ( PLWHA ) , yet prior research has not tested causal associations . This paper describes the challenges , methods , and baseline sample of the Housing and Health Study , a longitudinal , multi-site , r and omized controlled trial investigating the effects of providing immediate rental housing assistance to PLWHA who were homeless or at severe risk of homelessness . Primary outcomes included HIV disease progression , medical care access and utilization , treatment adherence , mental and physical health , and risks of transmitting HIV . Across three study sites , 630 participants completed baseline sessions and were r and omized to receive either immediate rental housing assistance ( treatment group ) or assistance finding housing according to local st and ard practice ( comparison group ) . Baseline sessions included a question naire , a two-session HIV risk-reduction counseling intervention , and blood sample collection to measure CD4 counts and viral load levels . Three follow-up visits occurred at 6 , 12 , and 18 months after baseline . Participants were mostly male , Black , unmarried , low-income , and nearly half were between 40 and 49 years old . At 18 months , 84 % of the baseline sample was retained . The retention rates demonstrate the feasibility of conducting scientifically rigorous housing research , and the baseline results provide important information regarding characteristics of this understudied population that can inform future HIV prevention and treatment efforts OBJECTIVE Reductions in runaways ' sexual risk behaviors were evaluated in response to an intensive program to prevent human immunodeficiency virus ( HIV ) infection and the acquired immunodeficiency syndrome ( AIDS ) . DESIGN In a nonr and omized control trial , sexual risk behaviors among 78 runaways at one residential shelter who received up to 30 HIV/AIDS intervention sessions were compared with 67 runaways at a nonintervention shelter with sexual behaviors assessed at baseline and 3 and 6 months . SETTING Runaways were recruited from the only two publicly funded shelters in New York , NY . PARTICIPANTS The runaways were aged 11 to 18 years , 64 % female , and predominantly black or Hispanic . INTERVENTION The intervention addressed general knowledge about HIV/AIDS , coping skills , access to health care and other re sources , and individual barriers to safer sex . MAIN OUTCOME MEASURES Consistent condom use , a high-risk pattern of sexual behavior , and sexual abstinence over a 3-month time frame were assessed . MAIN RESULTS As the number of intervention sessions increased , runaways ' reports of consistent condom use increased significantly ( at 3 months , unique R2 = .06 , P less than .05 ; at 6 months , unique R2 = .09 , P less than .05 ) , and their reports of engaging in a high-risk pattern of sexual behavior decreased significantly ( at 3 months , unique R2 = .03 , P = .06 ; at 6 months , unique R2 = .04 , P less than .05 ) . Abstinence did not change . CONCLUSIONS The demonstrated effectiveness of the intensive HIV/AIDS program highlights the importance of enlarging the scope of most current HIV/AIDS prevention programs Background : People who are homeless and chronically alcoholic have increased health problems , use of emergency services and police contact , with a low likelihood of rehabilitation . Harm reduction is a policy to decrease the adverse consequences of substance use without requiring abstinence . The shelter-based Managed Alcohol Project ( MAP ) was created to deliver health care to homeless adults with alcoholism and to minimize harm ; its effect upon consumption of alcohol and use of crisis services is described as proof of principle . Methods : Subjects enrolled in MAP were dispensed alcohol on an hourly basis . Hospital charts were review ed for all emergency department ( ED ) visits and admissions during the 3 years before and up to 2 years after program enrolment , and the police data base was accessed for all encounters during the same periods . The results of blood tests were analyzed for trends . A question naire was administered to MAP participants and staff about alcohol use , health and activities of daily living before and during the program . Direct program costs were also recorded . Results : Seventeen adults with an average age of 51 years and a mean duration of alcoholism of 35 years were enrolled in MAP for an average of 16 months . Their monthly mean group total of ED visits decreased from 13.5 to 8 ( p = 0.004 ) ; police encounters , from 18.1 to 8.8 ( p = 0.018 ) . Changes in blood test findings were nonsignificant . All program participants reported less alcohol consumption during MAP , and subjects and staff alike reported improved hygiene , compliance with medical care and health . Interpretation : A managed alcohol program for homeless people with chronic alcoholism can stabilize alcohol intake and significantly decrease ED visits and police encounters This study tests components of Wong and Solomon ’s ( 2002 , Mental Health Services Research , 4(2 ) , 13–28 ) model of community integration , identifying both the dimensions and predictors of integration . It evaluates community integration among adults with psychiatric disabilities assigned r and omly to receive either independent scatter-site apartments with the Housing First approach ( experimental ) or services as usual ( control ) . Factor analysis supported a definition of community integration that includes psychological , physical , and social domains , but also suggested the existence of another factor , independence/self-actualization . Regression analysis suggested that choice and independent scatter-site housing were predictors of psychological and social integration respectively . Psychiatric hospitalization , symptomatology and participation in substance use treatment were also found to influence aspects of integration . We discuss several issues that future studies should explore including the possibility that the same factor can differentially influence discrete aspects of integration , the role of person – environment fit , integration that is not based in the neighborhood , and , finally , conceptions of community integration from the perspective of consumers themselves SETTING Few studies have examined strategies for optimizing adherence to latent tuberculosis infection ( LTBI ) treatment programs in homeless population s. OBJECTIVES 1 ) To compare the effectiveness of an intervention program employing nurse case management and incentives ( NCMI ) vs. a control program with st and ard care and incentives on completion of LTBI treatment ; and 2 ) to compare the impact of the two programs on tuberculosis ( TB ) knowledge among participants . DESIGN A prospect i ve , two-group site-r and omized design conducted among 520 homeless adults residing in the Skid Row region of Los Angeles from 1998 to 2003 , assessing completion rates of a 6-month isoniazid ( INH ) treatment program and change in TB knowledge . RESULTS Using intent-to-treat analysis , 62 % of participants in the intervention program , compared with 39 % of controls , completed the full 6-month course of LTBI treatment with INH . Logistic regression modeling revealed that intervention participants had three times greater odds of completing INH treatment than controls . TB knowledge improved in both programs , but the increase was greater among the intervention participants ( P < 0.001 ) . CONCLUSIONS Nurse case management combined with education , incentives , and tracking dramatically improves both adherence to LTBI treatment and TB knowledge in homeless persons compared to a st and ard approach of outreach and incentives OBJECTIVES To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults . We compared ( 1 ) biweekly directly observed preventive therapy using a $ 5 monetary incentive and ( 2 ) biweekly directly observed preventive therapy using a peer health adviser , with ( 3 ) usual care at the tuberculosis clinic . METHODS R and omized controlled trial in tuberculosis-infected homeless adults . Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed . RESULTS A total of 118 subjects were r and omized to the 3 arms of the study . Completion in the monetary incentive arm was significantly better than in the peer health adviser arm ( P = .01 ) and the usual care arm ( P = .04 ) , by log-rank test . Overall , 19 subjects ( 44 % ) in the monetary incentive arm completed preventive therapy compared with 7 ( 19 % ) in the peer health adviser arm ( P = .02 ) and 10 ( 26 % ) in the usual care arm ( P = .11 ) . The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm ( P = .005 ) and 2 months in the usual care arm ( P = .04 ) . In multivariate analysis , independent predictors of completion were being in the monetary incentive arm ( odds ratio , 2.57 ; 95 % CI , 1.11 - 5.94 ) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry ( odds ratio , 2.33 ; 95 % CI , 1.00 - 5.47 ) . CONCLUSIONS A $ 5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care . Living in a hotel or apartment at the start of treatment also predicted the completion of therapy This study evaluated the psychiatric symptoms , psychosocial problems , and treatment response of personality-disordered substance abusers receiving services within a homeless drop-in center . Fifty-two homeless clients were assessed after program admission and r and omly assigned to receive either individual psychotherapy focused on personality disorder and substance abuse relapse prevention ( dual-focus schema therapy [ DFST ] ) or st and ard group substance abuse counseling ( SAC ) . Client functioning was assessed using measures of personality disorder , psychiatric symptoms , early maladaptive schemas , interpersonal problems , and addiction-related psychosocial impairment . Therapy retention ( total weeks in treatment ) and utilization ( number of weeks in which sessions were attended ) were the primary outcomes . Although rates of cluster B personality disorders were comparable to other substance dependent sample s , clusters A and C disorders were disproportionately more common . Clients reported significant psychiatric symptoms , criminality , and psychosocial impairment , yet made limited lifetime use of mental health services . Overall , there was greater utilization of individual DFST than group SAC . However , clients with more severe personality disorder symptoms demonstrated better utilization of SAC than DFST OBJECTIVE The effectiveness of two types of service programs in ameliorating homelessness among individuals with severe mental illness was compared . METHODS Homeless persons with severe mental illness were recruited into the study on their entry into one of two types of homeless service programs . The first was a comprehensive housing program , in which consumers received guaranteed access to housing , housing support services , and case management . The second was a program of case management only , in which consumers received specialized case management services . In a quasi-experimental or nonr and om-assignment design , participants responded to instruments measuring housing status , mental health symptoms , substance use , physical health , and quality of life at baseline ( program entry ) and at six months and 12 months after entry . The baseline interview was completed by 152 participants and at least one of the two follow-up interviews by 108 participants . High- , medium- , and low-impairment subgroups , based on psychiatric symptoms and degree of alcohol and illegal drug use , were formed by means of a propensity score subclassification . RESULTS Persons with high psychiatric symptom severity and high substance use achieved better housing outcomes with the comprehensive housing program than with case management alone . However , persons with low and medium symptom severity and low levels of alcohol and drug use did just as well with case management alone . CONCLUSIONS The results suggest that the effectiveness , and ultimately the cost , of homeless services can be improved by matching the type of service to the consumer 's level of psychiatric impairment and substance use rather than by treating mentally ill homeless persons as a homogeneous group OBJECTIVES We examined the longitudinal effects of a Housing First program for homeless , mentally ill individuals ' on those individuals ' consumer choice , housing stability , substance use , treatment utilization , and psychiatric symptoms . METHODS Two hundred twenty-five participants were r and omly assigned to receive housing contingent on treatment and sobriety ( control ) or to receive immediate housing without treatment prerequisites ( experimental ) . Interviews were conducted every 6 months for 24 months . RESULTS The experimental group obtained housing earlier , remained stably housed , and reported higher perceived choice . Utilization of substance abuse treatment was significantly higher for the control group , but no differences were found in substance use or psychiatric symptoms . CONCLUSIONS Participants in the Housing First program were able to obtain and maintain independent housing without compromising psychiatric or substance abuse symptoms OBJECTIVES We examined the efficacy of the Healthy Living Program in reducing risky sexual behavior and substance use among adults with HIV infection who were marginally housed ( i.e. , homeless at some point over a 37-month period ) . METHODS We had previously conducted a r and omized controlled trial with 936 adults living with HIV infection . In that study , 3 intervention modules of 5 sessions each addressed different goals : reducing risky sexual acts and drug use , improving the quality of life , and adhering to healthful behaviors . Participants were interviewed at baseline and at 5 , 10 , 15 , 20 , and 25 months ; 746 completed 4 or more assessment s. In this study , we analyzed sexual behavior and drug use outcomes for the 35 % ( n = 270 of 767 ) of participants who were considered marginally housed . RESULTS Among the marginally housed participants , there were significantly greater reductions in unprotected risky sexual acts , the number of sexual partners of HIV negative or unknown serostatus , alcohol or marijuana use , and hard drug use among the intervention group than among the control group . CONCLUSIONS Intensive , skill-focused intervention programs may improve the lives of marginally housed adults living with HIV infection Homeless youth face various health challenges . The effectiveness of a short intervention to promote sexual health in 572 homeless 16—23-year-olds ( M = 19.467 + 1.89 ) was conducted using a quasi-experimental repeated measures design . Data collected at three time points ( pre-intervention , immediately post-intervention and follow-up ) via laptop computers were analyzed using multivariate general linear mixed models . A significant condition by time interaction was found for self-reported AIDS/STD knowledge ; intervention participants had higher scores at first post-test . Females scored significantly higher on cognitive and behavioral outcomes while males reported significantly more sexual risk-taking behaviors . Findings support gender-specific interventions OBJECTIVE Clients with co-occurring severe mental and substance use disorders are at high risk of institutionalization and other adverse outcomes . Although integrated mental health and substance abuse treatment is becoming a st and ard clinical approach for such clients , the optimal method for delivering integrated treatment remains unclear . METHOD This study compared integrated treatment delivered within two different models of community-based case management ( assertive community treatment and st and ard clinical case management ) . A total of 198 clients in two urban sites who had co-occurring disorders and were homeless or unstably housed were r and omly assigned to one of two treatment conditions and were followed for three years . RESULTS Participants in both treatment conditions improved over time in multiple outcome domains , and few differences were found between the two models . Decreases in substance use were greater than would be expected given time alone . At the site that had higher rates of institutionalization , clients who received st and ard case management were more likely to be institutionalized . However , in the site that had lower rates of institutionalization , no differences in the rate of institutionalization were found between the two treatment conditions . CONCLUSIONS Integrated treatment can be successfully delivered either by assertive community treatment or by st and ard clinical case management CONTEXT Homeless adults , especially those with chronic medical illnesses , are frequent users of costly medical services , especially emergency department and hospital services . OBJECTIVE To assess the effectiveness of a case management and housing program in reducing use of urgent medical services among homeless adults with chronic medical illnesses . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted at a public teaching hospital and a private , nonprofit hospital in Chicago , Illinois . Participants were 407 social worker-referred homeless adults with chronic medical illnesses ( 89 % of referrals ) from September 2003 until May 2006 , with follow-up through December 2007 . Analysis was by intention-to-treat . INTERVENTION Housing offered as transitional housing after hospitalization discharge , followed by placement in long-term housing ; case management offered on-site at primary study sites , transitional housing , and stable housing sites . Usual care participants received st and ard discharge planning from hospital social workers . MAIN OUTCOME MEASURES Hospitalizations , hospital days , and emergency department visits measured using electronic surveillance , medical records , and interviews . Models were adjusted for baseline differences in demographics , insurance status , prior hospitalization or emergency department visit , human immunodeficiency virus infection , current use of alcohol or other drugs , mental health symptoms , and other factors . RESULTS The analytic sample ( n = 405 [ n = 201 for the intervention group , n = 204 for the usual care group ] ) was 78 % men and 78 % African American , with a median duration of homelessness of 30 months . After 18 months , 73 % of participants had at least 1 hospitalization or emergency department visit . Compared with the usual care group , the intervention group had unadjusted annualized mean reductions of 0.5 hospitalizations ( 95 % confidence interval [ CI ] , -1.2 to 0.2 ) , 2.7 fewer hospital days ( 95 % CI , -5.6 to 0.2 ) , and 1.2 fewer emergency department visits ( 95 % CI , -2.4 to 0.03 ) . Adjusting for baseline covariates , compared with the usual care group , the intervention group had a relative reduction of 29 % in hospitalizations ( 95 % CI , 10 % to 44 % ) , 29 % in hospital days ( 95 % CI , 8 % to 45 % ) , and 24 % in emergency department visits ( 95 % CI , 3 % to 40 % ) . CONCLUSION After adjustment , offering housing and case management to a population of homeless adults with chronic medical illnesses result ed in fewer hospital days and emergency department visits , compared with usual care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00490581 Data are reported on drug use among cocaine-dependent homeless persons who participated in a clinical trial that compared day treatment only ( DT , n = 69 ) with day treatment plus abstinent-contingent housing and work ( DT+ , n = 72 ) . Drug use was measured with multiple weekly urine toxicologies . Compared with DT participants , more DT+ participants established abstinence , maintained abstinence for longer duration s , were marginally significantly more likely to lapse , and significantly less likely to relapse . Of all participants who established abstinence and then relapsed , DT+ participants relapsed later and were more likely to reestablish abstinence . These analyses yield information on the processes involved in the manner in which drug use changes as a result of abstinent-contingent housing and work Runaway youth are 6–12 times more likely to become infected with HIV than other youth . Using a quasi-experimental design , the efficacy of an HIV prevention program was evaluated over 2 years among 2 groups of runaways : ( 1 ) those at 2 shelters who received Street Smart , an intensive HIV intervention program , and ( 2 ) youth at 2 control shelters . Street Smart provided youth with access to health care and condoms and delivered a 10-session skill-focused prevention program based on social learning theory to youth . Prior to analysis of the intervention 's outcomes , propensity scores were used to identify comparable subgroups of youth in the intervention ( n = 101 ) and control conditions ( n = 86 ) . Compared to females in the control condition , females in the intervention condition significantly reduced their unprotected sexual acts at 2 years and alcohol use , marijuana use , and the number of drugs used over 12 months . Male adolescents in the intervention condition showed significant reductions in marijuana use over 6 months compared to control youth . Adolescent HIV prevention programs must proactively identify mechanisms for maintaining behavior change over the long-term , and innovative research design s are needed to allow examination of agency-level interventions This study measured effectiveness of behavioral day treatment plus abstinence contingent housing and work therapy ( DT+ ) versus behavioral day treatment alone ( DT ) . A r and omized controlled trial assessed participants at baseline , 2 and 6 months . Participants ( N=110 ) met criteria for cocaine abuse or dependence , non-psychotic mental disorders , and homelessness . DT+ achieved greater abstinence at 2 and 6 months and more days housed at 6 months than DT . Effectiveness of DT+ was demonstrated , with greatest impacts on abstinence outcomes . Results replicated earlier work demonstrating effectiveness of behavioral day treatment and contingency management as an effective combination for cocaine abusing homeless persons OBJECTIVE To test the effect of living in group housing rather than independent apartments on executive functioning , verbal memory and sustained attention among formerly homeless persons with serious mental illness and to determine whether substance abuse modifies this effect . METHOD In metropolitan Boston , 112 persons in Department of Mental Health shelters were r and omly assigned to group homes ( " Evolving Consumer Households " , with project facilitator , group meetings , resident decision-making ) or independent apartments . All were case managed . A neuropsychological test battery was administered at baseline , at 18 months ( Time 2 ) , with an 81 % follow-up rate , and at 48 months ( Time 3 ) , with a 59 % follow-up rate . Hierarchical Linear Modeling was applied to executive functioning -- assessed with the Wisconsin Card Sorting Test (Perseverations)-Logical Memory story recall , and an auditory Continuous Performance Test ( CPT ) for sustained attention . Subject characteristics were controlled . RESULTS When moved to group homes , subjects without a lifetime substance abuse history improved on Perseverations , while those who moved to independent apartments deteriorated on Perseverations . Across the two housing conditions , subjects showed no change in Perseverations , but improved on Logical Memory story recall and the CPT . CONCLUSIONS Type of housing placement can influence cognitive functioning ; notably , socially isolating housing is associated with weakened executive functioning . Substance abuse significantly diminishes environmental effects . These are important factors to consider in housing placement and subsequent treatment While many studies provide useful information on the risk behaviors in which homeless youth engage , few prior studies evaluate Human Immunodeficiency Virus ( HIV ) risk related reduction strategies . In this study , homeless youth ( n = 180 ) were recruited from a drop-in center and r and omly assigned to one of two conditions , either an integrated individual cognitive-behavioral treatment and HIV prevention intervention that focused on skills building and education or to treatment as usual . All youth were assessed at entry into the program and at 3 and 6 month follow-up points . Findings showed an interaction between treatment condition , age and time . In the interaction , youth assigned to the integrated treatment reported greater condom usage than youth assigned to treatment as usual , with younger youth assigned to treatment as usual showing no change in condom use . The number of sexual partners reported by youth in both treatment conditions was also reduced over time . However , youth in both conditions continued to engage in other high-risk behaviors . The integrated treatment findings are promising and suggest that interventions which target both HIV risk behavior in addition to other life areas ( substance use , mental health and housing ) among homeless youth may be necessary in order to significantly impact high-risk behaviors among this unique group Shelter data in a recent study revealed discharges from psychiatric facilities to shelters or the street occurred at least 194 times in 2002 in London , Ontario , Canada . This problem must be addressed to reduce the disastrous effects of such discharge , including re-hospitalization and prolonged homelessness . An intervention was developed and tested to prevent homelessness associated with discharge directly to no fixed address . A total of 14 participants at-risk of being discharged without housing were enrolled , with half r and omized into the intervention group . The intervention group was provided with immediate assistance in accessing housing and assistance in paying their first and last month 's rent . The control group received usual care . Data was collected from participants prior to discharge , at 31 and 6-months post-discharge . All the individuals in the intervention group maintained housing after 3 and 6 months . All but one individual in the control group remained homeless after 3 and 6 months . The exception joined the sex trade to avoid homelessness . The results of this pilot were so dramatic that r and omizing to the control group was discontinued . Discussion s are underway to routinely implement the intervention . Systemic improvements can prevent homelessness for individuals being discharged from psychiatric wards Background : Hepatitis B virus ( HBV ) infection constitutes a major health problem for homeless persons . Ability to complete an HBV vaccination series is complicated by the need to prioritize competing needs , such as addiction issues , safe places to sleep , and food , over health concerns . Objectives : The objectives of this study were to evaluate the effectiveness of a nurse-case-managed intervention compared with that of two st and ard programs on completion of the combined hepatitis A virus ( HAV ) and HBV vaccine series among homeless adults and to assess sociodemographic factors and risk behaviors related to the vaccine completion . Methods : A r and omized , three-group , prospect i ve , quasi-experimental design was conducted with 865 homeless adults residing in homeless shelters , drug rehabilitation sites , and outdoor areas in the Skid Row area of Los Angeles . The programs included ( a ) nurse-case-managed sessions plus targeted hepatitis education , incentives , and tracking ( NCMIT ) ; ( b ) st and ard targeted hepatitis education plus incentives and tracking ( SIT ) ; and ( c ) st and ard targeted hepatitis education and incentives only ( SI ) . Results : Sixty-eight percent of the NCMIT participants completed the three-series vaccine at 6 months , compared with 61 % of SIT participants and 54 % of SI participants . NCMIT participants had almost 2 times greater odds of completing vaccination than those of participants in the SI program . Completers were more likely to be older , to be female , to report fair or poor health , and not to have participated in a self-help drug treatment program . Newly homeless White adults were significantly less likely than were African Americans to complete the vaccine series . Discussion : The use of vaccination programs incorporating nurse case management and tracking is critical in supporting adherence to completion of a 6-month HAV/HBV vaccine . The finding that White homeless persons were the least likely to complete the vaccine series suggests that programs tailored to address their unique cultural issues are needed The main purpose of the study was to determine whether a peer-support community programme would reduce relapse rates among clients recovering from substance addictions and homelessness and result in increased perceived community affiliation , supportive behaviours , self-determination and quality of life . Mixed methods were utilized including semi-structured interviews , participant observation and a pretest/post-test to evaluate changes on the quality of life rating , the Medical Outcomes Study -Social Support Survey , and the Volitional Question naire . Data from the prior year 's permanent supportive housing programme were used for comparison of relapse rates . Significant reduction of risk of relapse was found in clients who participated in the programme . Significant differences were found on three subscales of the Medical Outcomes Study -Social Support Survey . Improvement that did not reach statistical significance was seen on the quality of life rating . Qualitative evidence supported improvements in perceived community affiliation and supportive behaviours . Evidence suggests that a peer-supported community programme focused on self-determination can have a significant positive impact on recovery from substance addictions and homelessness . Limitations include a small sample size and lack of a r and omized control group The authors tested the hypotheses that neuropsychological functioning would improve after homeless persons with severe and persistent mental illness were provided with housing and that executive functioning would improve more among those placed in group homes than among those placed in independent apartments . A total of 114 persons with serious and persistent mental illness who were stable residents of homeless shelters completed neuropsychological testing and were r and omly assigned to group homes or independent apartments ; 91 participants ( 52 assigned to group homes and 39 assigned to independent apartments ) were retested after 18 months . Overall neuropsychological functioning improved significantly across the full study sample . Executive performance , measured by the Wisconsin Card Sorting Test , decreased significantly among persons assigned to independent apartments and increased , but not significantly , among those assigned to group homes . The findings suggest that providing housing for persons who have severe and persistent mental illness improves cognitive functioning but that independent living may diminish executive functioning Homelessness affects HIV risk and health , but little is known about the longitudinal effects of rental assistance on the housing status and health of homeless and unstably housed people living with HIV/AIDS . Homeless/unstably housed people living with HIV/AIDS ( N = 630 ) were r and omly assigned to immediate Housing Opportunities for People with AIDS ( HOPWA ) rental assistance or customary care . Self-reported data , CD4 , and HIV viral load were collected at baseline , 6 , 12 , and 18 months . Results showed that housing status improved in both groups , with greater improvement occurring in the treatment group . At 18 months , 51 % of the comparison group had their own housing , limiting statistical power . Intent-to-treat analyses demonstrated significant reductions in medical care utilization and improvements in self-reported physical and mental health ; significant differential change benefiting the treatment group was observed for depression and perceived stress . Significant differences between homeless and stably housed participants were found in as-treated analyses for health care utilization , mental health , and physical health . HOPWA rental assistance improves housing status and , in some cases , health outcomes of homeless and unstably housed people living with HIV/AIDS OBJECTIVE This study examined whether outcomes in housing , clinical status , and well-being of persons with severe mental illness and a history of homelessness differ between those in supported housing and those in community residences , two housing arrangements that substantially differ in the level of independence that is offered to its tenants . METHODS A quasi-experimental 18-month follow-up study was conducted with 157 persons newly entering supported housing and community residences . The housing models accepted persons with similar illness characteristics and homelessness histories , so that the inability to r and omly assign tenants to housing types could be compensated for by propensity scoring methods . Tenure in housing was examined by using survival models . Analyses of other outcomes used hierarchical linear and regression models in both intent-to-treat ( N=139 ) and true-stayer ( N=80 ) analyses . RESULTS Tenure in housing did not differ by housing type . Substantial proportions of tenants in both models remained housed during the follow-up period . Tenants in supported housing reported greater housing satisfaction in terms of autonomy and economic viability . Over time some tenants in supported housing reported greater feelings of isolation . Independent of housing type , symptoms of depression or anxiety at housing entry increased the risk of poorer outcomes . CONCLUSIONS The models of supported housing were viable portals of entry into community housing for homeless persons , even for consumers with characteristics indicating that they would have been more likely to be placed in community residences . The results suggest that greater clinical attention should be paid to persons who exhibit depression or anxiety when entering housing BACKGROUND Case management ( CM ) coordinates care for persons with complex health care needs . It is not known whether CM is effective at improving biological outcomes among homeless and marginally housed persons with human immunodeficiency virus ( HIV ) infection . Our goal was to determine whether CM is associated with reduced acute medical care use and improved biological outcomes in homeless and marginally housed persons with HIV infection . METHODS We conducted a prospect i ve observational cohort study in a probability-based community sample of HIV-infected homeless and marginally housed adults in San Francisco , California . The primary independent variable was CM , defined as none or rare ( any CM in < or=25 % of quarters in the study ) , moderate ( > 25 % but < or=75 % ) , or consistent ( > 75 % ) . The dependent variables were 3 self-reported health service use measures ( receipt of primary care , emergency department visits and hospitalizations , and antiretroviral therapy adherence ) and 2 biological measures ( increase in CD4(+ ) cell count of > or=50 % and geometric mean HIV load of < or=400 copies/mL ) . RESULTS In multivariate models , CM was not associated with increased primary care , emergency department use , or hospitalization . Moderate CM , compared with no or rare CM , was associated with an adjusted beta coefficient of 0.13 ( 95 % confidence interval [ CI ] , 0.02 - 0.25 ) for improved antiretroviral adherence . Consistent CM ( adjusted odds ratio [ AOR ] , 10.7 ; 95 % CI , 2.3 - 49.6 ) and moderate CM ( AOR , 6.5 ; 95 % CI , 1.3 - 33.0 ) were both associated with > or=50 % improvements in CD4(+ ) cell count . CM was not associated with geometric HIV load < 400 copies/mL when antiretroviral therapy adherence was included in the model . Study limitations include a lack of r and omization . CONCLUSION CM may be a successful method to improve adherence to antiretroviral therapy and biological outcomes among HIV-infected homeless and marginally housed adults OBJECTIVES Housing typically is not provided to homeless persons during drug abuse treatment . We examined how treatment outcomes were affected under 3 different housing provision conditions . METHODS We studied 196 cocaine-dependent participants who received day treatment and no housing ( NH ) , housing contingent on drug abstinence ( ACH ) , or housing not contingent on abstinence ( NACH ) . Drug use was monitored with urine testing . RESULTS The ACH group had a higher prevalence of drug abstinence than the NACH group ( after control for treatment attendance ) , which in turn had a higher prevalence than the NH group . All 3 groups showed significant improvement in maintaining employment and housing . CONCLUSIONS The results of this and previous trials indicate that providing abstinence-contingent housing to homeless substance abusers in treatment is an efficacious , effective , and practical intervention . Programs to provide such housing should be considered in policy initiatives Despite the increase in consumer-driven interventions for homeless and mentally ill individuals , there is little evidence that these programs enhance psychological outcomes . This study followed 197 homeless and mentally ill adults who were r and omized into one of two conditions : a consumer-driven “ Housing First ” program or “ treatment as usual ” requiring psychiatric treatment and sobriety before housing . Proportion of time homeless , perceived choice , mastery , and psychiatric symptoms were measured at six time points . Results indicate a direct relationship between Housing First and decreased homelessness and increased perceived choice ; the effect of choice on psychiatric symptoms was partially mediated by mastery . The strong and inverse relationship between perceived choice and psychiatric symptoms supports expansion of programs that increase consumer choice , thereby enhancing mastery and decreasing psychiatric symptoms Background : Research on addiction treatment utilization in indigent sample s mainly has been retrospective , without measures of addictive consequences , social network influences , and motivation . Prospect i ve assessment of factors influencing utilization could inform policy and clinical care . Objective : We sought to identify factors associated with utilization of addiction treatment and mutual help groups among substance-dependent persons with high rates of homelessness . Research and Methods : This was a prospect i ve cohort of patients detoxified from alcohol or drugs at baseline who were followed for 2 years in a r and omized clinical trial of linkage to primary care ( n = 274 ) . Outcomes included utilization of Inpatient/Residential , Outpatient , Any Treatment , and Mutual Help Groups . Predictor variables in longitudinal regression analyses came from the literature and clinical experience , organized according to theoretical categories of Need , and non-Need ( eg , Predisposing and Enabling ) . Results : Many subjects used Inpatient/Residential ( 72 % ) , Outpatient ( 62 % ) , Any Treatment ( 88 % ) or Mutual Help Groups ( 93 % ) at least once . In multivariable analyses , addictive consequences ( odds ratio [ OR ] 1.38 , 95 % confidence interval [ CI ] 1.12–1.71 ) , motivation ( OR 1.32 , 95 % CI 1.09–1.60 ) , and female gender ( OR 1.80 , 95 % CI 1.13–2.86 ) were associated with most treatment types ( ORs are for Any Treatment ) . Homelessness was associated with Residential/Inpatient ( for Chronically Homeless vs. Housed , OR 1.75 , 95 % CI 1.04–2.94 ) . Living with one 's children ( OR 0.51 , 95 % CI 0.31–0.84 ) and substance-abusing social environment ( OR 0.65 , 95 % CI 0.43–0.98 ) were negatively associated with Any Treatment . Conclusions : In this cohort of substance-dependent persons , addictive consequences , social network variables , and motivation were associated with treatment utilization . Non-need factors , including living with one 's children and gender , also were significant There is a paucity of literature on direct treatment outcomes for impoverished minority population s. The current study supports the feasibility of successfully treating women for depressive symptoms in community setting s where they typically seek care , adding to the small but growing direct knowledge base in this area . The sample of the 2-site study consisted of 91 women seeking treatment for depressive complaints at a homeless shelter program and a municipal hospital psychiatric clinic for Latino patients . Participants were r and omly assigned to either a 16-week cognitive-behavioral group or a 16-week supportive/exploratory group for depression . Best- practice features with this population were integrated throughout . Findings showed that both treatment conditions were equally effective in decreasing depressive symptoms ( BDI , CES-D ) up to 4 months after treatment termination . These changes were paralleled by improvements in self-reported physical health ( Duke Physical Profile ) . No significant differences between treatment conditions were found . Directives for next steps in the current research agenda are offered in efforts to broaden the direct evidence base for treating vulnerable urban women at high risk for depression and other forms of mental illness Objective The authors pilot a smoking-cessation outreach for the homeless that extends medical students ’ tobacco cessation education . Method In this prospect i ve study , second-year medical students administered cognitive behavior therapy or unstructured support to homeless subjects to help them quit smoking . Self-report and biological measures ( carbon monoxide ) of smoking taken at baseline and follow-up were analyzed using t tests to determine intervention efficacy . Results Out of 11 enrolled subjects , six completed the protocol and all decreased their smoking frequency . The mean rate of smoking dropped significantly from 19 to nine cigarettes per day when pooling all subjects , and carbon monoxide mean level decreased from 28.0 to 20.2 . Conclusions The homeless subjects who received counseling from medical students significantly reduced their smoking frequency . Subject recruitment and retention were challenges , but a close partnership with local homeless shelters and the addition of pharmacotherapy could improve outcomes and are recommended for future efforts ABSTRACT This study compared the costs and outcomes associated with three treatment programs that served 149 individuals with dual disorders ( i.e. , individuals with co-occurring severe mental illness and substance use disorders ) who were homeless at baseline . The three treatment programs were : Integrated Assertive Community Treatment ( IACT ) , Assertive Community Treatment only ( ACTO ) , and st and ard care ( Control ) . Participants were r and omly assigned to treatment and followed for a period of 24 months . Clients in the IACT and ACTO programs were more satisfied with their treatment program and reported more days in stable housing than clients in the Control condition . There were no significant differences between treatment groups on psychiatric symptoms and substance use . The average total costs associated with the IACT and Control conditions were significantly less than the average total costs for the ACTO condition This study investigated Behavioral Day Treatment attendance in relation to treatment outcome among homeless persons dependent on crack-cocaine . Participants ( N = 141 ) were 72.3 % male and 82.7 % African American . Days attended , activities attended , and follow-up rates over a 12-month period were positively affected by the more attractive treatment of providing immediate , rent-free , abstinent-contingent housing during a 2-month Behavioral Day Treatment program . Results replicated previous findings that abstinence is a function of treatment attendance and more treatment is associated with greater abstinence . The loss of predictive power at long-term follow-up , limitations of a retrospective design , need to identify most predictive therapeutic activity types , and potential influence of mental disorders were discussed . Analytical techniques used in this study allows for the planning , predictability , and measurement of drug abuse treatment success as a function of service utilization OBJECTIVES We assessed the health impact of a housing and case management program , the Chicago Housing for Health Partnership , for homeless people with HIV . METHODS HIV-positive homeless in patients at a public hospital ( n = 105 ) were r and omized to usual care or permanent housing with intensive case management . The primary outcome was survival with intact immunity , defined as CD4 count > or = 200 and viral load < 100,000 . Secondary outcomes were viral loads , undetectable viral loads , and CD4 counts . RESULTS Outcomes were available for 94 of 105 enrollees ( 90 % ) . Of 54 intervention participants , 35 ( 65 % ) reached permanent housing in program housing agencies . After 1 year , 55 % of the intervention and 34 % of the usual care groups were alive and had intact immunity ( P = .04 ) . Seventeen intervention ( 36 % ) and 9 usual care ( 19 % ) participants had undetectable viral loads ( P = .051 ) . Median viral loads were 0.89 log lower in the intervention group ( P = .03 ) . There were no statistical differences in CD4 counts . CONCLUSIONS Homelessness is a strong predictor of poor health outcomes and complicates the medical management of HIV . This housing intervention improved the health of HIV-positive homeless people This study examined whether homelessness predicted earlier resumption of substance use after detoxification , and sought evidence concerning the impact of post-detoxification stabilization programs among homeless and nonhomeless individuals . Kaplan-Meier plots and proportional hazards models were used to determine the association between homelessness , stabilization program use , and recurrent substance use in a prospect i ve cohort of persons entering inpatient detoxification ( n=470 ) . Among 254 persons available at 6 months , 76 % reported recurrent substance use . Homeless persons not using stabilization programs experienced the highest hazard of return to substance use after detoxification , Hazard Ratio ( HR ) 1.26 , 95 % CI ( 0.88 , 1.80 ) . Homeless persons using these programs had the lowest rate of return to substance use : HR 0.61 , 95 % CI ( 0.40 , 0.94 ) . A similar impact of stabilization programs was not seen among nonhomeless subjects . Post-detoxification stabilization programs were associated with improved outcomes for homeless addicted persons . This treatment modality may slow the " revolving door " phenomenon of relapse after detoxification among homeless persons Homeless youth are at increased risk for hepatitis B virus ( HBV ) infection and HBV vaccine coverage is poor in this group . The purpose of our study was to determine if a shelter-based HBV vaccine program in children and adolescents 2–18 years of age with a r and omized controlled trial using a culturally appropriate HBV video could increase HBV vaccine coverage rates . Subjects were r and omized to an 8 min HBV video or a control , smoking prevention video . Before exposure to the videos , HBV knowledge , and demographics were assessed in caregivers and adolescents . HBV vaccine no. 1 was offered to all subjects who did not produce a vaccine record ; subsequently , an accurate HBV vaccine history was obtained from medical providers . Subjects were asked to return 1 and 3 months after visit 1 , HBV vaccine was offered to all with incomplete coverage , and HBV knowledge was reassessed . There were 328 children and adolescents cared for by 170 caregivers enrolled in the study . One hundred and four had incomplete HBV vaccine coverage . Data are reported for all family units with at least one subject needing vaccine . There were 53 children and adolescents r and omized to the HBV video vs. 51 to the smoking video . HBV knowledge scores of caregivers improved at Visit no. 2 vs. no. 1 in the HBV video group ( p = 0.01 ) but not in the smoking group ( p = 0.82 ) . Similar results were observed for adolescents in the HBV video group ( p = 0.05 ) but not in the smoking group ( p = 0.40 ) . Exposure to the HBV video vs the smoking video had a significant effect on return rates for vaccine at Visit no. 2 ( 59 vs. 31 % ; p = 0.05 ) but not at Visit no. 3 ( 47 vs. 18 % , p = 0.06 ) . The shelter-based vaccine program was very effective in increasing HBV coverage rates in the entire group of 328 children and adolescents enrolled in the study , from 68 % coverage at baseline to 85 % at the conclusion of the study . We conclude that shelter-based HBV vaccine programs can be highly effective in increasing vaccine coverage rates in older children and adolescents . A brief exposure to a culturally appropriate HBV video improves HBV knowledge and may improve return rates for vaccine Treatment efficacy for homeless substance abusers ( primarily crack cocaine ) was studied in a r and omized control design with subjects ( n = 176 ) assigned to usual care ( UC ) or an enhanced day treatment program plus abstinent contingent work therapy and housing ( EC ) . Subjects met DSM-III-R criteria for Substance Use Disorder and McKinny Act criteria for homelessness . UC involved weekly individual and group counseling . EC involved a day treatment program consisting of daily attendance , transportation , lunch , manualized psychoeducational groups , and individual counseling . A total of 131 ( 74.4 % ) subjects ( 62 UC and 69 EC ) were treated and followed . UC subjects attended 28.5 % and EC attended 48.4 % of expected treatment during the first 2 months . After 2 months , EC subjects experienced up to 4 months of abstinent contingent work therapy ( 44.9 % of EC subjects ) and housing ( 37.7 % of EC subjects ) , with day treatment available two afternoons per week . Longitudinal Wei-Lachin analyses of medians ( reported alcohol use , days homeless and employed ) and proportions ( cocaine toxicologies ) were conducted across 2- , 6- , and 12-month follow-up points . EC had 36 % fewer positive cocaine toxicologies at 2-months and 18 % fewer at 6-months than UC with regression toward baseline at 12-months . EC had 8 days fewer days of reported alcohol use in the past 30 days , 52 fewer days homeless in the past 60 days , and 10 more days employed in the past 30 days from baseline to the 12-months . UC showed no changes except a temporary increase in employment at 6-months . This is one of the first demonstrations that homeless cocaine abusers can be retained and effectively treated PURPOSE Current Centers for Disease Control ( CDC ) guidelines recommend that sexually transmitted disease ( STD ) screening measures for high-risk population s such as homeless youth prioritize testing in out-of-clinic setting s and incorporate new approaches to STD eradication , such as field-delivered testing and treatment and patient-delivered partner therapy ( PDPT ) . Our non-medically trained research staff offered field-based STI testing , field-delivered therapy , and PDPT to homeless youth in the context of a longitudinal study . METHODS A total of 218 ethnically diverse ( 34 % female ) 15 - 24-year-old homeless youth recruited from street sites in San Francisco completed an audio computer-administered self-interview survey and provided a first-void urine sample for testing for chlamydia ( CT ) and gonorrhea ( GC ) . Youth testing positive were offered field-delivered therapy and PDPT . A r and om subset of 157 youth was followed prospect ively , of whom 110 ( 70 % ) were interviewed and 87 ( 55 % ) retested at six months . RESULTS At baseline , 99 % of youth in the study consented to STI testing , of whom 6.9 % and .9 % tested positive for CT and GC , respectively . Ninety-four percent of positive youth were treated , 50 % within one week . The incidence rate for CT was 6.3 per 100 person-years ( 95 % confidence interval [ CI ] : 1.3 - 18.4 ) and for GC was 4.2 per 100 person-years ( 95 % CI : .5 - 15.2 ) . None of the youth treated by study staff and tested six months later ( n = 6 ) had CT or GC on follow-up testing ( 95 % CI : 0 - 131.3 ) . CONCLUSIONS Field-delivered testing and field-delivered therapy are feasible , acceptable and effective interventions for the diagnosis and treatment of STDs in homeless youth . These measures along with PDPT may decrease rates of subsequent reinfection In an attempt to reduce homelessness and substance abuse , Chicago graduates of short-term inpatient substance abuse programs who lacked domiciles were placed into one of three conditions : ( 1 ) a case management only intervention ( n = 96 ) , ( 2 ) a case management with supported housing intervention ( n = 136 ) , or ( 3 ) a control condition ( n = 187 ) that allowed access to normal aftercare in the community . The two treatment interventions used a " progressive independence " approach , which focuses on simultaneously ameliorating tangible needs and clinical problems . Multivariate analyses suggest that subjects in both treatment interventions experienced lower levels of substance abuse and higher levels of residential stability than subjects in the control condition , as measured over the course of a year . Further analysis suggests that retention was improved by the focus on immediate tangible re sources , substance abuse was reduced by both the support of outpatient substance abuse treatment and the promulgation of changes in coping styles , and residential stability was increased by both the focus on access to income maintenance benefits and help with location of housing This research examined the impact of including a supportive person on the outcomes of two culturally sensitive AIDS education programs , an education-only ( traditional ) program and a program combining education with self-esteem and coping enhancement ( specialized ) . Research participants in this quasi-experimental study included 241 homeless women , who were r and omly assigned by residence ( drug treatment program or shelter ) to one of four treatment groups . The outcomes measured at baseline , 6 , and 12 months were risk behaviors , cognitive factors , and psychological functioning . Study results demonstrated significant improvements at both 6 and 12 months for the entire sample in all psychological , behavioral and cognitive outcome variables except active coping . Women in the specialized program improved more on AIDS knowledge and reduction in non-injection drug use than did those in the traditional program , but their active coping scores declined . Participation of a supportive person did not appear to have any effect on outcome This study , which tested two motivational interviewing treatment approaches , assessed the feasibility of conducting a community-based smoking cessation intervention among homeless smokers . Participants ( N = 46 ) were recruited from multiple facilities in the Kansas City area and were r and omized to two counseling conditions in which they received five individual motivational interviewing sessions , six group meetings , and their choice of 8 weeks of 21-mg nicotine patch or 4-mg nicotine lozenge . The two counseling conditions consisted of motivational interviewing targeted either to smoking behaviors exclusively ( smoking only ) or to smoking and other addictions or life events that could affect ability to quit ( smoking plus ) . Group meetings were design ed to provide educational information and social support . Measures of feasibility assessed included the proportion of participants who returned for r and omization among those eligible , adherence to prescribed nicotine replacement therapies , retention rates at the week 26 final study visit , and biochemically verified 7-day abstinence at week 26 . Most participants ( 69.6 % ) chose nicotine patches , and 32 % of those participants reported using at least four patches per week . Carbon monoxide verified 7-day abstinence rates in the smoking-only and smoking-plus groups were 13.04 % and 17.39 % ( ns ) , respectively , at week 8 and 8.70 % and 17.39 % ( ns ) , respectively , at week 26 . Participants who used at least four patches per week were more likely to have quit at 8 weeks than were those who used fewer patches ( 33.3 % vs. 10.5 % , p = .30 ) . Results support the feasibility of conducting a smoking cessation intervention among homeless smokers . Findings also show promising effects for nicotine replacement therapy and counseling in this population . Developing programs to improve smoking cessation outcomes in underserved population s is an essential step toward achieving national health objectives and for ultimately reducing tobacco-related health disparities Comprehensive intervention for homeless , street living youth that addresses substance use , social stability , physical and mental health issues has received very little attention . In this study , street living youth aged 14 - 22 were recruited from a drop-in center and r and omly assigned to the Community Reinforcement Approach ( CRA ) or treatment as usual ( TAU ) through a drop-in center . Findings showed that youth assigned to CRA , compared to TAU , reported significantly reduced substance use ( 37 % vs. 17 % reduction ) , depression ( 40 % vs. 23 % ) and increased social stability ( 58 % vs. 13 % ) . Youth in both conditions improved in many other behavioral domains including substance use , internalizing and externalizing problems , and emotion and task oriented coping . This study indicates that homeless youth can be engaged into treatment and respond favorably to intervention efforts . However , more treatment development research is needed to address the barriers associated with serving these youth Communities across the United States have initiated plans to end chronic homelessness . In many of these communities , addiction treatment programs remain the default point of entry to housing and services . This study examined the percentage of cocaine-using homeless persons ( all with psychiatric distress ) attaining stable housing and employment 12 months after entering a r and omized trial of intensive behavioral day treatment , plus one of the following for 6 months : no housing ; housing contingent on drug abstinence ; housing not contingent on abstinence . Of 138 participants , the percentages with stable housing and employment at 12 months were 34.1 and 33.3 % , respectively . Analyses suggested superior outcomes in trial arms that offered housing as part of the behavioral treatment . The majority of participants , however , did not achieve housing or employment , in part because of the limited capacity of the local housing programs to accommo date persons who had not achieved perfect abstinence . The findings demonstrate a helpful role for addiction treatment and suggest the need for services to support housing of persons who reduce but do not eliminate all substance use OBJECTIVES This r and omized clinical trial assessed whether a community-based representative payee program that was coordinated with psychiatric care from the Department of Veterans Affairs was more effective than customary treatment . METHODS In the experimental condition representative payeeship was provided by a community agency that worked to enroll clients and coordinate payeeship with clinical care through communication with clinical staff . The control condition consisted of customary clinical care that included the typical availability of representative payeeship . Hypotheses were that , compared with the control group , the experimental group would experience greater enrollment in a representative payee program ; improved residential status ; improved quality of life , including fewer symptoms of mental illness ; less substance abuse ; and improved money management . Participants were interviewed at baseline and at six and 12 months . Outcomes were analyzed with analysis of covariance by using covariates from the baseline . RESULTS A total of 184 participants were enrolled at baseline ( 94 in the experimental group and 90 in the control group ) . A total of 152 interviews were completed at six months , and 149 were completed at 12 months . At 12 months , 31 percent of patients in the experimental group and 14 percent of those in the control group were receiving representative payee services . At 12 months , significant positive effects were observed for the experimental group on enrollment in a representative payeeship , alcohol and drug use , quality of life , and money management . Residential status approached significance . CONCLUSIONS Use of a coordinated representative payee program was found to be effective in improving outcomes at 12 months . Although this evidence supports the wider implementation of a coordinated representative payee program , only 31 percent of the experimental group had their money banked with a representative payee . Therefore , future studies should focus on achieving a better underst and ing of the causal components of the intervention Abstract The purpose of the present study was to obtain preliminary data on the effectiveness of a faith-based treatment adjunct for cocaine-using homeless mothers in residential treatment . The Bridges intervention utilizes various Black church communities to provide culturally-relevant group activities and individual mentoring from volunteers . Eighteen women who were recent treatment admissions were r and omly assigned to receive St and ard Treatment plus Bridges or St and ard Treatment with an Attention Control . Participants were assessed at intake and three and six months after intake . Bridges treatment result ed in significantly better treatment retention ( 75 % vs. 20 % at six months ) than st and ard residential treatment alone . In addition , Bridges produced superior outcomes at the six month followup assessment on a secondary measure of cocaine abstinence . Creating a community of social support through Black churches appears feasible and promising , and may be a cost-effective means of providing longer-term post-treatment support for cocaine-addicted women OBJECTIVE The objective of this study was to test whether an intensive case management intervention would be effective with a group of homeless chronic public inebriate clients . The primary goals of the case management were to improve the financial and residential stability of the clients and to reduce their use of alcohol . METHOD Subjects ( N = 298 , 81 % male ) were interviewed at baseline , r and omly assigned to treatment and control conditions and given follow-up interviews at 6-month intervals for 2 years . Case management services were provided for the duration of the project . Follow-up rates for the first three interviews averaged 82 % . RESULTS Repeated measures MANCOVAs showed significant group differences favoring the case-managed group in all three areas targeted by the intervention : total income from public sources , nights spent in " own place " out of the previous 60 nights and days drinking out of the previous 30 days . The results held whether the three variables were analyzed jointly or separately and for alternative measures of drinking and homelessness . Although statistically significant , the group differences are generally not large . CONCLUSIONS The results indicate that case management had a beneficial effect on the clients receiving it . This effect may have been the result of an increase in services received by the case-managed clients This study compared two contemporary approaches to linking housing and mental health services . In the integrated housing program , case management and housing services were provided by teams within a single agency and were closely coordinated . In the parallel housing condition , case management services were provided by mobile assertive community treatment teams and housing by routine community-based l and lords . Adults with severe mental illness who were at high risk for homelessness ( n = 121 ; 72.7 % schizophrenia spectrum ) were assigned r and omly to integrated or parallel housing services and followed for 18 months . Integrated housing services led to more days of stable housing and greater life satisfaction than parallel housing services , especially for male participants . Integrated housing services were also associated with greater reductions in psychiatric symptoms . Closer integration between clinical and housing services , and greater use of supervised living setting s , led to more time in stable housing for participants in the integrated housing services condition and was associated with greater gains in several outcome domains |
2,315 | 21,943,365 | Conclusion NBI does not improve detection of colorectal polyps when compared to conventional colonoscopy ( Australian New Zeal and Clinical Trials Registry ACTRN12610000456055 ) | Background A colonoscopy may frequently miss polyps and cancers .
A number of techniques have emerged to improve visualization and to reduce the rate of adenoma miss . | Context How often does colonoscopy miss adenomas ? Contribution During a multicenter screening trial , experienced colonoscopists performed same-day optical ( OC ) and virtual colonoscopy ( VC ) on 1233 asymptomatic adults . Optical colonoscopy performed without knowledge of the VC findings missed 55 of 511 polyps ; 21 of these polyps were adenomas measuring 6 mm or greater . Adenomas missed by OC were usually on the proximal side of a fold or near the anal verge . Virtual colonoscopy missed 14 % of the adenomas that measured 6 mm or greater that were de-tected by OC . Implication s Neither OC nor VC is a perfect test : Each misses 10 % to 14 % of adenomas that measure 6 mm or greater . The Editors Optical colonoscopy ( OC ) is widely accepted as the gold st and ard for detecting colorectal neoplasia ( 1 , 2 ) . However , even in the most experienced h and s , this skilled examination is underst and ably not infallible . Retrospective analysis has suggested that the OC miss rate for adenomas 10 mm or greater is approximately 10 % ( 3 ) . More recently , prospect i ve back-to-back or t and em colonoscopy studies have reported miss rates for 10-mm adenomas ranging from 0 % to 6 % ( 4 , 5 ) . However , in addition to evaluating relatively small population s of patients with a high prevalence of polyps , a notable weakness common to these studies was that they used OC as its own reference st and ard . In a large , prospect i ve , multicenter trial that was primarily intended to evaluate the performance of virtual colonoscopy ( VC ) in asymptomatic adults ( 6 ) , we also had a unique opportunity to evaluate the adenoma miss rate on OC by segmentally unblinding the results from same-day VC . By using a reference st and ard other than OC itself for comparison , we could uncover lesions that may be systematic ally missed on repeated colonoscopies . These data not only provide novel insight into OC miss rates but also indicate the relative blind spots where more attention could be focused . Methods Study Design The institutional review boards at all 3 participating medical centers approved the study protocol for same-day VC and OC , and all patients provided written informed consent . We recruited asymptomatic adults who were referred for colorectal cancer screening . Exclusion criteria were a positive stool guiaic test result or iron deficiency anemia within the past 6 months ; rectal bleeding , hematochezia , or unintentional weight loss of more than 10 pounds within the past 12 months ; OC within the past 10 years or barium enema within the past 5 years ; personal history of adenomatous polyps , colorectal cancer , or inflammatory bowel disease ; and family history of familial adenomatous polyposis or nonpolyposis cancer syndromes . Between May 2002 and June 2003 , 1253 asymptomatic adults enrolled in the study . Eight patients were excluded because of failure to reach the cecum at OC , 6 patients were excluded because of inadequate colonic preparation , and another 6 patients were excluded because of computed tomography ( CT ) system failure . The final study group comprised 1233 asymptomatic adults ( 728 men and 505 women ; mean age , 57.8 years ) who successfully completed same-day VC and OC . Study participants underwent colonic preparation with oral intake of 90 mL of phospho-soda and 10 mg of bisacodyl . To opacify residual colonic fluid and stool for VC examination , patients also consumed dilute oral contrast as previously described ( 7 ) . Our CT protocol and VC technique have also been detailed previously ( 6 ) . To briefly summarize , we obtained supine and prone CT acquisitions on multidetector scanners after patient-controlled rectal insufflation of room air . One of 6 trained radiologists interpreted VC studies by using a commercially available CT colonography system ( Viatronix V3D-Colon , version 1.2 , Viatronix , Inc. , Stony Brook , New York ) . We used the 3-dimensional endoluminal fly-through view primarily for detecting polyps and 2-dimensional images for confirmation and problem solving . We measured polyps on the 3-dimensional view and recorded them by segment ( cecum , ascending colon , hepatic flexure , transverse colon , splenic flexure , descending colon , sigmoid colon , or rectum ) . We defined the proximal colon as including the cecum to the splenic flexure . We prospect ively rated diagnostic confidence for each detected lesion on a 3-point scale ( most certain , intermediate , and least certain ) . One of 17 experienced colonoscopists performed OC immediately after VC interpretation by using st and ard commercial video colonoscopes ( Olympus , Inc. , Melville , New York ) . The colonoscope was advanced to the cecum and then sequentially withdrawn into more distal segments for polyp detection . The colonoscopist measured polyps by using a calibrated linear probe , which is more accurate than either visual or biopsy forceps estimation ( 8) . Our polyp-matching algorithm requires VC and OC agreement according to size ( within a 50 % margin of error ) and location ( within the same or adjacent segment ) . After the colonoscopist evaluated a given segment , a study nurse unblinded the VC results for the previous segment . For any suspected polyp seen on VC that measured 5 mm or greater but was not seen on the initial blinded OC , the colonoscopist closely reexamined that segment and could review the VC images for guidance . We sent all retrieved polyps for histologic examination . For all cases in which a colorectal neoplasm measuring 6 mm or greater was found on second-look OC , we retrospectively review ed both the VC and OC images . We recorded polyp characteristics , such as size , morphologic characteristic ( sessile , pedunculated , or flat ) , and location on VC . If the polyp was situated on a colonic fold on VC , we further subcategorized it as being located on the back ( proximal ) side , front ( distal ) side , or edge of the fold . We analyzed both supine and prone VC sets for all cases . The primary reason that diminutive polyps measuring 5 mm at VC were included for potential unblinding at OC was that , given the relative error in polyp measurement , such polyps found on second-look OC might , in fact , measure 6 mm or greater . This allows for more accurate assessment of the OC miss rate at the 6-mm threshold . We did not include unblinded polyps that measured 5 mm or less on both VC and OC examinations in the final analysis . All study participants completed a detailed question naire on their personal and family medical history . For the purpose s of this study , particular attention was given to the question about previous abdominal or pelvic surgery , since adhesions could conceivably result in a more difficult colonoscopic examination . Statistical Analysis Prospect i ve OC performance was compared against the enhanced reference st and ard of second-look OC after segmental unblinding of VC results . We estimated exact binomial 95 % CIs for OC miss rates . We used the chi-square test to compare the frequency of previous abdominal surgery among patients with and without polyps missed at OC and also to compare the OC miss rates among the 3 medical centers . We calculated the 95 % CIs by using Stata software , version 7.0 for Windows ( Stata Corp. , College Station , Texas ) , and performed the chi-square tests by using SAS software , version 8.0 for Windows ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The funding source had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results The performance characteristics of VC from this prospect i ve , multicenter screening trial , using OC as the reference st and ard , have been previously reported ( 6 ) . Our technique of segmental unblinding also allows for a separate assessment of OC by using the blinded VC results for comparison , which is the focus of this study . We identified 1310 polyps at OC in the 1233 asymptomatic adults ; 511 ( 39.0 % ) of these polyps measured 5 mm or greater ( Figure 1).Of these 511 polyps , 55 ( 10.8 % ) were found only on second-look OC after segmental unblinding of VC results . Twenty-four ( 43.6 % ) of the 55 unblinded lesions were nonadenomatous , including 16 hyperplastic polyps . Of the 31 missed neoplasms , 10 adenomas that measured only 5 mm were excluded from further analysis because of their diminutive size ( 9 ) . Including unblinded lesions , 554 adenomas were detected on OC in this screening sample ; 210 of these measured 6 mm or greater and 51 measured 10 mm or greater . Figure 1 . Polyp flowchart . In 20 patients ( 17 men and 3 women ; mean age , 58.2 years ) , 21 adenomas measuring 6 mm or greater ( range , 6 mm to 17 mm ; mean , 8.1 mm ) were found on OC only after the VC results were unblinded , which represent the lesions of primary interest for this study ( Table ) . The corresponding adenoma miss rate on prospect i ve OC examination was 10.0 % ( 95 % CI , 6.3 % to 14.9 % ) ( 21 of 210 adenomas ) at a 6-mm cutoff . The 20 patients with missed adenomas that measured 6 mm or greater represented only 1.6 % of the study sample ( 20 of 1233 patients ) but 11.9 % of patients with adenomas 6 mm or greater ( 20 of 168 patients ) . At 8-mm and 10-mm thresholds , the OC adenoma miss rates by polyp were 10.5 % ( CI , 5.2 % to 18.5 % ) ( 10 of 95 adenomas ) and 11.8 % ( CI , 4.4 % to 23.9 % ) ( 6 of 51 adenomas ) , respectively . The 10 patients with missed adenomas 8 mm or greater represented 12.2 % ( 10 of 82 patients ) of all patients with neoplasms of this size or greater ; the 6 patients with missed adenomas 8 mm or greater represented 12.5 % of all patients with neoplasms 10 mm or greater . Table . Characteristics of Neoplasms Missed at Prospect i ve Colonoscopic Evaluation Seventeen ( 81.0 % ) of the 21 unblinded neoplasms 6 mm or greater were tubular adenomas , 3 ( 14.3 % ) were tubulovillous adenomas , and 1 ( 4.8 % ) was an adenocarcinoma . Seven ( 33.3 % ) of the 21 unblinded polyps were classified as advanced lesions ( that is , size 10 mm or high- grade dysplasia , prominent villous component , or focus of malignancy ) . There were 15 sessile lesions , 4 pedunculated lesions , and 2 flat BACKGROUND & AIMS Colonoscopic polypectomy is considered effective for preventing colorectal cancer ( CRC ) , but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated . We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high- grade dysplasia . METHODS Patients were drawn from 3 adenoma chemoprevention trials . All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions . We identified patients subsequently diagnosed with invasive cancer or adenoma with high- grade dysplasia . The timing , location , and outcome of all cases of cancer and high- grade dysplasia identified are described and risks associated with their development explored . RESULTS CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years ( incidence , 1.74 cancers/1000 person-years ) . The cancers were located in all regions of the colon ; 10 were at or proximal to the hepatic flexure . Although most of the cancers ( 84 % ) were of early stage , 2 participants died of CRC . Seven patients were diagnosed with adenoma with high- grade dysplasia during follow-up . Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high- grade dysplasia . CONCLUSIONS CRC is diagnosed in a clinical ly important proportion of patients following complete colonoscopy and polypectomy . More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed Background and aims : Colonoscopy is an established method of colorectal cancer screening , but has an adenoma miss rate of 10–20 % . Detection rates are expected to improve with optimised visualisation methods . This prospect i ve r and omised study evaluated narrow-b and imaging ( NBI ) , a new technique that may enhance image contrast in colon adenoma detection . Methods : Eligible patients presenting for diagnostic colonoscopy were r and omly assigned to undergo wide-angle colonoscopy using either conventional high-resolution imaging or NBI during instrument withdrawal . The primary outcome parameter was the difference in the adenoma detection rate between the two techniques . Results : A total of 401 patients were included ( mean age 59.4 years , 52.6 % men ) . Adenomas were detected more frequently in the NBI group ( 23 % ) than in the control group ( 17 % ) with a number of 17 colonoscopies needed to find one additional adenoma patient ; however , the difference was not statistically significant ( p = 0.129 ) . When the two techniques were compared in consecutive subgroups of 100 study patients , adenoma rates in the NBI group remained fairly stable , whereas these rates steadily increased in the control group ( 8 % , 15 % , 17 % , and 26.5 % , respectively ) . Significant differences in the first 100 cases ( 26.5 % versus 8 % ; p = 0.02 ) could not be maintained in the last 100 cases ( 25.5 % versus 26.5 % , p = 0.91 ) . Conclusions : The increased adenoma detection rate means of NBI colonoscopy were statistically not significant . It remains speculative as to whether the increasing adenoma rate in the conventional group may have been caused by a training effect of better polyp recognition on NBI BACKGROUND AND STUDY AIM Patients with longst and ing ulcerative colitis are at increased risk of developing colorectal cancer . Colonoscopic surveillance is advised , but the detection of neoplasia by conventional colonoscopy is difficult . The aim of this study was to compare the accuracy of narrow-b and imaging ( NBI ) , a new imaging technique , with st and ard colonoscopy for the detection of neoplasia in patients with longst and ing ulcerative colitis . PATIENTS AND METHODS This was a prospect i ve , r and omized , crossover study of 42 patients with longst and ing ulcerative colitis . All participants underwent NBI and conventional colonoscopy with at least 3 weeks between the procedures . R and omization determined the order of the examinations . Targeted biopsies were taken during both procedures ; additional r and om biopsies were taken at conventional colonoscopy only . The number of patients with neoplasia detected by targeted biopsies was used to assess the sensitivity for each technique . RESULTS With NBI , 52 suspicious lesions were detected in 17 patients , compared with 28 suspicious lesions in 13 patients detected during conventional colonoscopy . Histopathological evaluation of targeted biopsies revealed 11 patients with neoplasia : in four patients the neoplasia was detected by both techniques , in four patients neoplasia was detected only by NBI , and in three patients neoplasia was detected only by conventional colonoscopy ( P = 0.705 ) . Aside from targeted biopsies , 1522 r and om biopsies were taken . These revealed one additional patient with dysplasia that was not detected by either technique . CONCLUSIONS The sensitivity of the studied first-generation NBI system for the detection of patients with neoplasia seems to be comparable to conventional colonoscopy , although more suspicious lesions were found during NBI . We believe that it is still too early to stop taking additional r and om biopsies at surveillance colonoscopy in patients with ulcerative colitis BACKGROUND AND AIM Flat and depressed colorectal neoplastic lesions can be difficult to identify using conventional colonoscopy techniques . Narrow-b and imaging ( NBI ) provides unique views especially of mucosal vascular network and helps in visualization of neoplasia by improving contrast . The aim of this study was to assess the feasibility of using NBI for colorectal neoplasia screening . METHODS Forty-seven consecutive patients , who underwent high definition colonoscopy ( HDC ) screening examinations revealing neoplastic lesions , were enrolled in our prospect i ve study . No biopsies or resections were performed during the initial HDC , but patients in whom lesions were detected underwent further colonoscopies using NBI , with the results of the first examination blinded from the colonoscopist . They then received appropriate treatment . We compared diagnostic detection rates of neoplastic lesions for HDC and NBI procedures using total number of all identified neoplastic lesions as reference st and ard . RESULTS Altogether , 153 lesions were detected and analyzed in 43 patients . Mean diagnostic extubation times were not significantly different ( P = 0.18 ) , but the total number of lesions detected by NBI was higher ( 134 vs 116 ; P = 0.02 ) . Based on macroscopic type , flat lesions were identified more often by NBI ( P = 0.04 ) . As for lesion size , only flat lesions < 5 mm were detected more frequently ( P = 0.046 ) . Lesions in the right colon were identified more often by NBI ( P = 0.02 ) , but NBI missed two flat lesions > or= 10 mm located there . CONCLUSIONS Narrow b and imaging colonoscopy may represent a significant improvement in the detection of flat and diminutive lesions , but a future multi-center controlled trial should be conducted to fully evaluate efficacy for screening colonoscopies Background and aims Issues on colonoscopy quality are crucial to reduce the advanced neoplasia miss rate of colonoscopy . Recently , a > 6-min withdrawal time has been recommended . However , the relative prevalence of polyp detected during insertion and withdrawal phases of colonoscopy is unknown . Therefore , we design ed this prospect i ve , endoscopic study . Material s and methods Three hundred and sixty-eight patients with 396 adenomas were selected from a consecutive colonoscopic series of 1,205 cases . Detection rates of adenomas , advanced adenomas , and cancer according to withdrawal and insertion phases of colonoscopy , also subgrouping polyps for size and location , were compared . Results Thirty-two ( 74 % ) advanced adenomas and 21 ( 95 % ) cancers were detected during the insertion , being only 11 ( 26 % ) and one ( 5 % ) identified during withdrawal , respectively . This was mainly due to a higher detection of > 10 mm polyps during insertion than during withdrawal ( 75 % versus 25 % ) . Conclusions Most advanced neoplasia are detected during the insertion . Although withdrawal time has been shown to be important , the scope insertion phase related to polyp detection should be specifically addressed BACKGROUND & AIMS Colonoscopy , using either a transparent retractable extension device or narrow b and imaging , is thought to improve colon adenoma detection . We compared the abilities of a transparent retractable extension device and narrow b and imaging to detect colorectal adenomas . METHODS One hundred and seven patients with colonic adenomas that were detected by traditional colonoscopy were r and omly assigned to groups that underwent a second colonoscopy that used either a transparent retractable extension or narrow b and imaging ; adenomas were removed . The principal outcome parameters were the number , size , shape , and location of adenomas detected . The patients ' demographic characteristics , indications for colonoscopy , and cecal intubation times were similar between groups . RESULTS Use of the transparent retractable extension result ed in detection of 31 % more adenomas than the initial procedure ( P < .0001 ) . The majority of newly discovered adenomas were sessile ( 79 % ; 26/33 ) and less than 5 mm in size ( 73 % ; 24/33 ) . There was no significant increase in adenoma detection ( 5 % ) between first colonoscopy and second colonoscopy using narrow b and imaging . Additional adenomas were found in 40.7 % of patients that were examined using the transparent hood ( 22/54 ) versus 13.2 % of those examined using narrow b and imaging ( 7/53 ) ( P = .0028 ) . CONCLUSIONS Colonoscopy with a transparent retractable extension significantly improved the adenoma detection rate compared with repeat colonoscopy using narrow b and imaging BACKGROUND & AIMS Narrow b and imaging ( NBI ) is an imaging technique that allows a better definition of capillary pattern and improves the contrast between adenomas and the surrounding mucosa . Conflicting data exist on the ability of NBI to improve detection of colonic neoplasm ; the impact of NBI is being tested in several screening scenarios . We evaluated whether the routine use of NBI , compared with white light ( WL ) , during the withdrawal phase of screening colonoscopy improved adenoma detection . METHODS This r and omized controlled study included consecutive 50- to 69-year-old patients with positive immunologic fecal occult blood tests . They were r and omly assigned to groups that were examined with WL ( n = 108 ) or NBI ( n = 103 ) during the withdrawal phase of their colonoscopies . The primary end point was the adenoma detection rate . The prevalence of non-polypoid and the total number of adenomas were also evaluated . RESULTS The number of total and mean per-patient adenomas were 201 ( 1.95 + /- 2.3 ) and 198 ( 1.83 + /- 2.1 ) in the NBI and WL groups , respectively ( P = .69 ) . The adenoma detection rates were 57.3 % for patients examined by NBI and 58.3 % for those examined by WL ( P = .88 ) . A total of 41 non-polypoid adenomas were identified ( 26 in the NBI and 15 in the WL groups , P = .16 ) . The flat adenoma detection rates were 21.4 % and 9.3 % in the NBI and WL groups , respectively ( P = .019 ) . CONCLUSIONS The routine use of NBI in screening colonoscopy did not increase the adenoma detection rate . NBI seems to improve the detection of flat adenomas , although additional studies are necessary BACKGROUND Colorectal neoplasm is rapidly increasing in Asia , but a guideline for screening is not available . OBJECTIVE To evaluate the characteristics of colorectal neoplasm in asymptomatic Asian subjects . DESIGN Prospect i ve cohort study . SETTING Multinational multicenters , including both primary and referral centers in Asia . PATIENTS A total of 860 consecutive asymptomatic adults undergoing screening colonoscopy in 11 Asian cities from July 2004 to December 2004 . Patients under 16 years old ; those patients with a colorectal resection history , colonoscopies , or barium enema within 5 years ; symptoms suggestive of colorectal diseases ; and those who had undergone surveillance colonoscopy were excluded . MAIN OUTCOME MEASUREMENTS The incidence and distribution of colorectal neoplasm and advanced neoplasm . RESULTS The mean age ( + /-SD ) was 54.4+/-11.6 years ; 471 were men ( 54.8 % ) . The prevalence of colorectal neoplasm and advanced neoplasm was 18.5 % and 4.5 % , respectively . Male sex , advancing age , and a family history of colorectal cancer were risk factors for advanced neoplasm . Of the 168 patients with colorectal neoplasm , 76 had distal neoplasm only ( 45.2 % ) , 66 had proximal neoplasm only ( 39.3 % ) , and 26 had both proximal and distal neoplasms ( 15.5 % ) . Although the presence of distal advanced neoplasm was a significant risk factor for proximal advanced neoplasm , 14 of the 758 subjects without distal neoplasm had proximal advanced neoplasm ( 1.8 % ) . LIMITATIONS The small number of enrolled subjects , especially from certain ethnic groups . CONCLUSIONS The overall prevalence of advanced colorectal neoplasm in asymptomatic Asians is comparable with the West . Male sex , advancing age , and a family history of colorectal cancer were associated with a higher risk of advanced neoplasm Objective : Colonoscopy , the “ gold st and ard ” screening test for colorectal cancer ( CRC ) , has known diagnostic limitations . Advances in endoscope technology have focused on improving mucosal visualisation . In addition to increased angle of view and resolution features , recent colonoscopes have non-white-light optics , such as narrow b and imaging ( NBI ) , to enhance image contrast . We aim ed to study the neoplasia diagnostic characteristics of NBI , by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light ( WL ) . Design : R and omised controlled trial . Setting : US Veterans hospital . Patients : Elective colonoscopy adults . Intervention : We r and omly assigned patients to undergo a colonoscopic examination using NBI or WL . All patients underwent a second examination using WL , as the reference st and ard . Main outcome measures : The primary end point was the difference in the neoplasm miss rate , and secondary outcome was the neoplasm detection rate . Results : In 276 t and em colonoscopy patients , there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques . Of the 135 patients in the NBI group , 17 patients ( 12.6 % ; 95 % confidence interval ( CI ) 7.5 to 19.4 % ) had a missed neoplasm , as compared with 17 of the 141 patients ( 12.1 % ; 95 % CI 7.2 to 18.6 % ) in the WL group , with a miss rate risk difference of 0.5 % ( 95 % CI −7.2 to 8.3 ) . 130 patients ( 47 % ) had at least one neoplasm . Missed lesions with NBI showed similar characteristics to those missed with WL . All missed neoplasms were tubular adenomas , the majority ( 78 % ) was ⩽5 mm and none were larger than 1 cm ( one-sided 95 % CI up to 1 % ) . Nonpolypoid lesions represented 35 % ( 13/37 ) of missed neoplasms . Interpretation : NBI did not improve the colorectal neoplasm miss rate compared to WL ; the miss rate for advanced adenomas was less than 1 % and for all adenomas was 12 % . The neoplasm detection rates were similar high using NBI or WL ; almost a half the study patients had at least one adenoma . Clinical trials.gov identifier : BACKGROUND Colonoscopy is the preferred screening method for colorectal cancer . However , it has a substantial miss rate for colon polyps , and several techniques have been attempted to improve this limitation . Narrow-b and imaging ( NBI ) is a novel technology that enhances the visualization of surface mucosal and vascular patterns . OBJECTIVE The aim of this study was to determine the detection rate of additional polyps by NBI after removal of polyps visualized by st and ard white light colonoscopy ( WLC ) and to correlate the surface mucosal and vascular patterns with polyp histologic diagnosis . DESIGN This was a prospect i ve pilot feasibility study . SETTING Kansas City Veterans Affairs Medical Center . PATIENTS Subjects referred for screening colonoscopy were prospect ively enrolled . METHODS Subjects underwent colonoscopy after enrollment . After intubation of the cecum , colonic segments were sequentially examined , initially with WLC with removal of polyps followed by re-examination of the same segment with NBI . Additional polyps seen with NBI were photographed for their surface patterns and then removed . The total number of polyps visualized by WLC and NBI was calculated and the surface patterns were then correlated with polyp histologic features . RESULTS Forty patients were enrolled in the study , all men , 32 white . The mean age was 62 years . A total of 72 polyps were detected by WLC ( 43 tubular adenoma , 28 hyperplastic polyps ) , whereas NBI detected an additional 51 polyps , of which 29 were tubular adenomas and 22 were hyperplastic . Five different surface/vascular patterns were observed : fine capillary network with absent mucosal pattern , circular pattern with dots , round/oval pattern , tubular pattern , and gyrus pattern . The sensitivity , specificity , and overall accuracy of the first two patterns for hyperplastic polyps were 86 % , 96 % , and 92 % , respectively , and of the latter three patterns for tubular adenomas were 96 % , 86 % , and 92 % , respectively . CONCLUSIONS This pilot study demonstrates the feasibility of polyp detection and histologic correlation with NBI . These findings need to be confirmed in future r and omized controlled trials Purpose The introduction of reimbursement for screening colonoscopy in Germany more than one year ago raised concerns that the consequent workload might lead to underuse of diagnostic colonoscopy for symptomatic patients . Available appropriateness criteria for diagnostic colonoscopy have been rarely tested in a realistic outpatient setting . This study was design ed to test current appropriateness criteria for diagnostic colonoscopy to better select patients and potentially provide more capacity for screening cases . Secondary goals were yield and quality control in both the diagnostic and screening cases . Methods A prospect i ve study was initiated in 39 private- practice offices to collect data on consecutive colonoscopies conducted during a 6-day study period . A detailed question naire was developed to define indications and symptoms , and all findings at colonoscopy were recorded . Colonoscopies were further analyzed and stratified into a screening and a diagnostic group . In the diagnostic group , indications were assessed according to the current guidelines for appropriateness ( American Society for Gastrointestinal Endoscopy , European Panel for the Appropriateness of Gastrointestinal Endoscopy ) , and the results were correlated with the percentage of relevant findings ( tumors , inflammatory conditions ) . Results During the study period , 1,397 colonoscopies ( 57 percent screening , 43 percent diagnostic ) were analyzed ( male/female ratio = 39/61 percent ; mean age , 61 years ) . Fourteen percent and 37 percent , respectively , of the 605 diagnostic colonoscopies were regarded as inappropriate relative to the criteria of the American Society for Gastrointestinal Endoscopy and the European Panel for the Appropriateness of Gastrointestinal Endoscopy . However , the percentage of relevant inflammatory and neoplastic findings ( polyps , cancer , inflammatory bowel disease , benign strictures ) was only 5 to 10 percent higher in the appropriate group than in the inappropriate group . On the basis of these data , a hypothetical model for selecting appropriate indications was developed : if patients older than aged 50 years with pain , bleeding , and diarrhea , but not constipation , are regarded as having an appropriate indication , such an approach would save 20 percent of colonoscopies in these main indication groups ( bleeding , pain , diarrhea , constipation ) , with a hypothetical miss rate for relevant findings ( as defined above ) of 5 percent . Conclusions Currently used appropriateness criteria for diagnostic colonoscopy increase the yield of relevant findings but lead to a miss rate for relevant findings in the range of 10 to 15 percent . Simple selection criteria based on age and symptoms could be more suitable and should be tested in a larger group of patients BACKGROUND AND STUDY AIM Polyp miss rates during colonoscopy have been calculated in a few t and em or back-to-back colonoscopy studies . Our objective was to assess the adenoma miss rate while limiting technique or operator expertise biases , i. e. by performing a large multicenter study , with same-day back-to-back video colonoscopy , done by two different operators in r and omized order and blinded to the other examination . PATIENTS AND METHODS 294 patients at 11 centers were included . Among the 286 analyzable t and em colonoscopies , miss rates were calculated in both a lesion- and patient-based analysis . Each of these rates was determined for polyps overall , for adenomas , and then for lesions larger than 5 mm , and for advanced adenomas . Univariate and logistic regression analysis were performed to define independent variables associated with missed polyps or adenomas . RESULTS The miss rates for polyps , adenomas , polyps > or = 5 mm , adenomas > or = 5 mm , and advanced adenomas were , respectively , 28 % , 20 % , 12 % , 9 % and 11 % . None of the masses with a carcinomatous ( n = 3 ) or carcinoid component ( n = 1 ) was missed . The specific lesion miss rates for patients with polyps and adenomas were respectively 36 % and 26 % but the corresponding rates were 23 % and 9.4 % when calculated for all 286 patients . The diameter ( 1-mm increments ) and number of polyps ( > or = 3 ) were independently associated with a lower polyp miss rate , whereas sessile or flat shape and left location were significantly associated with a higher miss rate . Adequacy of cleansing , presence of diverticula , and duration of withdrawal for the first procedure were not associated with adenoma miss rate . CONCLUSIONS We confirm a significant miss rate for polyps or adenoma during colonoscopy . Detection of flat polyps is an issue that must be focused on to improve the quality of colonoscopy BACKGROUND AND STUDY AIMS Narrow b and imaging ( NBI ) with optical magnification is useful in predicting colon polyp histology . As magnifying endoscopes are not routinely available , we investigated the use of NBI and high definition white light imaging in determining polyp histology , using images obtained with colonoscopes without optical magnification . PATIENTS AND METHODS Images ( white light and NBI ) of colon polyps less than 10 mm in diameter were collected prospect ively from patients undergoing screening colonoscopy and digitally stored . Two endoscopists later review ed all images and predicted polyp histology as neoplastic or non-neoplastic using a modified Kudo classification . Comparison was made with histopathology . RESULTS Separate white light and NBI images of 80 polyps ( 49 neoplastic , 31 non-neoplastic ) from 63 patients were recorded . Mean polyp size was 5.1 + /- 2.1 mm ( 5.4 + /- 2.2 neoplastic ; 4.4 + /- 1.8 non-neoplastic ; P = 0.02 ) . In a pooled analysis , NBI correctly predicted neoplastic histology in 93 of 98 images ( sensitivity 95 % , positive predictive value [ PPV ] 94 % ) whereas white light did so in 58 of 98 images ( sensitivity 59 % , PPV 79 % ) . NBI correctly predicted non-neoplastic histology in 56 of 62 images ( specificity 90 % , negative predictive value [ NPV ] 92 % ) whereas white light did so in 47 of 62 images ( specificity 76 % , NPV 54 % ) . CONCLUSIONS NBI without optical magnification was more accurate in predicting colon polyp histology compared with white light imaging . Image quality and confidence in histology were significantly higher in the NBI group . NBI without optical magnification may be useful in predicting colon polyp histology Background . Detection and removal of adenomas by colonoscopy is an important means for preventing cancer ; however , small adenomas may be missed during colonoscopy . The narrow-b and imaging ( NBI ) system clearly enhances the microvasculature in neoplastic lesions , making it appear as a dark complex . Therefore , the NBI system may improve the detection of colonic neoplasias . However , no r and omized , controlled trials have evaluated the efficacy of a pan-colonic NBI system in adenoma detection . We conducted a r and omized , controlled trial to determine the efficacy of the pancolonic NBI system in adenoma detection . Methods . Two hundred forty-three patients were r and omized , 121 to conventional colonoscopy and 122 to pan-colonic NBI system . Demographics , indication for colonoscopy , and quality of preparation were similar between groups . Results . Extubation time was not significantly different between the conventional colonoscopy and pan-colonic NBI system . The proportions of patients with at least one adenoma and those with multiple adenomas were not significantly different between groups . However , the pan-colonic NBI system significantly increased the total number of adenomas detected ( P < 0.05 ) and the number of diminutive ( < 5 mm ) adenomas detected ( P < 0.05 ) . The pan-colonic NBI system allowed detection of more diminutive adenomas in the distal colon than did conventional colonoscopy ( P < 0.01 ) , and more patients in the NBI group had at least one diminutive adenoma than in the control group ( P < 0.05 ) . Conclusions . The pan-colonic NBI system improves the total number of adenomas detected , including significantly more diminutive adenomas , without prolongation of extubation time . These results indicate that routine use of the NBI system for surveillance of diminutive adenomas may be recommended BACKGROUND AND STUDY AIMS Narrow b and imaging ( NBI ) can accurately characterize colonic polyps using microvascular appearances . We aim ed to assess whether the Kudo pit pattern classification is accurate when used with NBI ( without dye-spray ) , and if microvascular appearances or NBI pit patterns maintain accuracy for polyp characterization at sizes < 10 mm . PATIENTS AND METHODS 116 polyps < 10 mm in size were detected in 62 patients undergoing surveillance colonoscopy . The polyps were prospect ively assessed using NBI and magnification for Kudo pit pattern ( III-V neoplastic , I-II non-neoplastic ) and vascular pattern intensity ( VPI ) , a measure of microvascular density ( strong VPI , neoplastic ; normal or weak VPI , non-neoplastic ) . Sensitivity , specificity , and accuracy were calculated and compared with results from histopathology . RESULTS The mean polyp size was 3.4 mm ( range 1 - 9 mm ) . Overall , NBI pit pattern sensitivity , specificity , and accuracy were 0.88 , 0.91 , and 89.6 % , respectively . Equivalent values for VPI were 0.94 , 0.89 , and 91.4 % . Results were similar when polyps were subdivided into diminutive polyps ( size < or= 5 mm ) and flat polyps . Combining both pit pattern and VPI improved the sensitivity ( 0.98 , P = 0.06 versus NBI pit pattern alone ) . There was very good agreement between NBI pit pattern and VPI for prediction of dysplasia ( kappa = 0.83 ) . No evidence of a learning curve for VPI was found . The NBI pit pattern was better than the VPI at subclassifying hyperplastic from other non-neoplastic polyps ( sensitivity 0.79 versus 0.56 , respectively , P = 0.02 ) , but accuracy was poor . CONCLUSION The NBI pit pattern and VPI are both highly accurate in characterizing neoplastic colonic polyps of < 10 mm , with VPI appearing to be simple to learn . NBI has the potential to replace conventional histology for small polyps |
2,316 | 24,403,259 | Manypre clinical studies demonstrated that everolimus had antitumor effects such as antiproliferation and antiangiogenesis .
However , some differences in the effects were observed among in vivo animal studies for HCC treatment .
Meanwhile , clinical studies demonstrated that the response rate of single-agent everolimus was low , though survival benefits could be expected .
Everolimus at the dose of 10 mg/day significantly increased the risk of the adverse events . | Everolimus is an orally administrated mammalian target of rapamycin ( mTOR ) inhibitor .
Several large-scale r and omized controlled trials ( RCTs ) have demonstrated the survival benefits of everolimus at the dose of 10 mg/day for solid cancers .
Furthermore , mTOR-inhibitor-based immunosuppression is associated with survival benefits for patients with hepatocellular carcinoma ( HCC ) who have received liver transplantation .
However , a low rate of tumor reduction and some adverse events have been pointed out .
This review summarizes the antitumor effects and adverse events of everolimus and evaluates its possible application in advanced HCC . | AIM Transcatheter arterial chemoembolization ( TACE ) is an established treatment for unresectable hepatocellular carcinoma ( HCC ) . However , it is unclear which chemotherapeutic agent should be selected for TACE . The aim of this study was to compare the efficacy of cisplatin ( CDDP ) with that of epirubicin ( EPI ) in TACE for patients with unresectable or relapsed HCC . METHODS We performed a historical cohort study involving 131 patients treated with a first TACE , defined as either an initial treatment for previously untreated HCC or a first treatment for relapsed HCC after curative resections or ablations . Efficacy was estimated as the response rate ( RR ) and it was adjusted for the confounding factors that were defined in this study . RESULTS The RR were 62.5 % ( 20/32 ) for the first TACE with CDDP and 51.5 % ( 51/99 ) for that with EPI . In the adjusted analysis for a history of hepatectomy , percutaneous treatment combined with TACE and tumor factors , the odds ratio was 1.72 ( 95 % confidence interval [ CI ] = 0.70 - 4.48 ) . However , a test for interaction between the number of tumors and the chemotherapeutic agent was statistically significant ( P = 0.016 ) . In multiple HCC , the RR were 66.7 % ( 10/17 ) for CDDP and 39.6 % ( 30/46 ) for EPI . The odds ratio was 4.11 ( 95 % CI = 1.14 - 17.2 ) . CONCLUSION CDDP may be more effective than EPI in TACE for multiple HCC . A r and omized controlled study is needed to clarify the efficacy of CDDP in TACE in patients with multiple HCC The prognosis of patients with hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) is extremely poor . The aim of this study was to eluci date the efficacy of hepatic arterial infusion chemotherapy ( HAIC ) for patients with advanced HCCs Sorafenib targets the Raf/mitogen-activated protein kinase , VEGF , and platelet-derived growth factor pathways and prolongs survival patients in advanced hepatocellular carcinoma ( HCC ) . Everolimus inhibits the mammalian target of rapamycin , a kinase overactive in HCC . To investigate whether the antitumor effects of these agents are additive , we compared a combined and sequential treatment regimen of everolimus and sorafenib with monotherapy . After hepatic implantation of Morris Hepatoma ( MH ) cells , rats were r and omly allocated to everolimus ( 5 mg/kg , 2 × /week ) , sorafenib ( 7.5 mg/kg/d ) , combined everolimus and sorafenib , sequential sorafenib ( 2 weeks ) then everolimus ( 3 weeks ) , or control groups . MRI quantified tumor volumes . Erk1/2 , 4E-BP1 , and their phosphorylated forms were quantified by immunoblotting . Angiogenesis was assessed in vitro by aortic ring and tube formation assays , and in vivo with Vegf-a mRNA and vascular casts . After 35 days , tumor volumes were reduced by 60 % , 85 % , and 55 % , relative to controls , in everolimus , the combination , and sequential groups , respectively ( P < 0.01 ) . Survival was longest in the combination group ( P < 0.001 ) . Phosphorylation of 4E-BP1 and Erk1/2 decreased after everolimus and sorafenib , respectively . Angiogenesis decreased after all treatments ( P < 0.05 ) , although sorafenib increased Vegf-a mRNA in liver tumors . Vessel sprouting was abundant in control tumors , lower after sorafenib , and absent after the combination . Intussusceptive angiogenic transluminal pillars failed to coalesce after the combination . Combined treatment with everolimus and sorafenib exerts a stronger antitumoral effect on MH tumors than monotherapy . Everolimus retains antitumoral properties when administered sequentially after sorafenib . This supports the clinical use of everolimus in HCC , both in combination with sorafenib or after sorafenib . Mol Cancer Ther ; 10(6 ) ; 1007–17 . © 2011 AACR In a prospect i ve , multicenter , open‐label study , de novo liver transplant patients were r and omized at day 30±5 to ( i ) everolimus initiation with tacrolimus elimination ( TAC Elimination ) ( ii ) everolimus initiation with reduced‐exposure tacrolimus ( EVR+Reduced TAC ) or ( iii ) st and ard‐exposure tacrolimus ( TAC Control ) . R and omization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection ( tBPAR ) . EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint ( tBPAR , graft loss or death at 12 months posttransplantation ) : 6.7 % versus 9.7 % ( −3.0 % ; 95 % CI −8.7 , 2.6 % ; p<0.001 for noninferiority [ 12 % margin ] ) . tBPAR occurred in 2.9 % of EVR+Reduced TAC patients versus 7.0 % of TAC Controls ( p = 0.035 ) . The change in adjusted estimated GFR from r and omization to month 12 was superior with EVR+Reduced TAC versus TAC Control ( difference 8.50 mL/min/1.73 m2 , 97.5 % CI 3.74 , 13.27 mL/min/1.73 m2 , p<0.001 for superiority ) . Drug discontinuation for adverse events occurred in 25.7 % of EVR+Reduced TAC and 14.1 % of TAC Controls ( relative risk 1.82 , 95 % CI 1.25 , 2.66 ) . Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 ( 95 % CI 1.03 , 3.00 ) . Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function , compared to a st and ard tacrolimus exposure regimen 12 months after liver transplantation Hepatocellular carcinoma ( HCC ) st and s as a major health problem worldwide . The management of advanced HCC , limited for a longtime by the disappointing results of conventional cytotoxic chemotherapies , has recently changed with the publication of the results of the Sorafenib Hepatocellular Carcinoma Assessment R and omized Protocol ( SHARP ) trial , which demonstrated an overall survival benefit over placebo in patients with advanced HCC . This study was further confirmed by the Asian-Pacific trial using sorafenib in Eastern patients . Those trials demonstrated that therapeutic benefits may derive from improving our knowledge of deregulated signaling pathways involved in HCC carcinogenesis . This review summarizes the results of clinical trials in which targeted therapies are currently evaluated aim ing to enlarge the therapeutic armamentarium for HCC in a near future We present the 12-month results of a prospect i ve trial of conversion from calcineurin inhibitors ( CNI ) to everolimus ( EVL ) in maintenance liver transplant ( LT ) recipients . Forty ( M : F = 28:12 ; 54.9 + /- 11 years ) patients were enrolled at a mean interval of 45.5 + /- 31.2 months from transplantation . Conversion was with EVL at a dosage of 0.75 mg b.i.d . , withdrawal of antimetabolites , and a 50%-per-week reduction of CNI to a complete stop within 4 weeks . The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI , death , and graft loss . Indication to conversion was deteriorating renal function in 36 ( 90 % ) . At 12 months , patient- and graft survival were 100 % and the success rate was 75 % ( 30/40 ) . Ten patients ( 25 % ) were failures : four ( 10 % ) for acute rejection ; three hepatitis C virus-RNA positive patients ( 7.5 % ) for hypertransaminasemia ; one ( 2.5 % ) for acute cholangitis ; and two ( 5 % ) due to persistent pruritus and oral ulcers . In patients on EVL monotherapy , at 12 months the mean change of calculated creatinine clearance ( cCrCl ) was 4.03 + /- 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl ( P < 0.0001 ) . Conversion from CNI to EVL is feasible in 75 % of the cases and associated with improvement in renal function for patients with higher baseline cCrCl Data on the conversion of patients to everolimus after liver transplantation are sparse . A multicenter , retrospective study followed 240 maintenance liver transplant patients to analyze the current indications for everolimus conversion , the employed regimens and exposure levels , and the impact on efficacy and safety . The mean time from transplantation to the introduction of everolimus was 4.9 ± 5.2 years . The mean everolimus trough level was 7.3 ± 4.1 ng/mL at month 1 and 8.1 ± 4.7 ng/mL at month 12 . At 12 months , 61.6 % of the patients were no longer receiving calcineurin inhibitor ( CNI ) therapy . The mean estimated glomerular filtration rate ( eGFR ) according to the Cockcroft-Gault formula was 64.2 ± 30.0 mL/minute on day 0 and 68.4 ± 32.5 mL/minute at month 12 ( P = 0.007 ) . Among patients with baseline serum creatinine levels ≥ 130 μmol/L , the eGFR values were 44.3 ± 15.7 mL/minute on day 0 and 53.7 ± 26.0 mL/minute at month 12 ( P = 0.003 ) . Four patients ( 1.6 % ) developed mild or moderate biopsy-proven acute rejection . Adverse events led to everolimus discontinuation in 12.9 % of the patients . After the initiation of everolimus , the mean white blood cell count decreased significantly , and the total cholesterol and triglyceride levels increased significantly . In this retrospective analysis of the largest cohort of maintenance liver transplant patients analyzed after their conversion to everolimus , more than 60 % of the patients were kept free of CNIs with a very low risk of acute rejection and with an acceptable safety profile . R and omized trials in which maintenance liver transplant patients are switched to everolimus in response to clinical indications or preemptively are warranted BACKGROUND Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin ( mTOR ) intracellular signaling pathway . In early studies , the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity . METHODS In this phase 3 , r and omized trial , we compared everolimus and exemestane versus exemestane and placebo ( r and omly assigned in a 2:1 ratio ) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease ( or both ) . The primary end point was progression-free survival . Secondary end points included survival , response rate , and safety . A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed . RESULTS Baseline characteristics were well balanced between the two study groups . The median age was 62 years , 56 % had visceral involvement , and 84 % had hormone-sensitive disease . Previous therapy included letrozole or anastrozole ( 100 % ) , tamoxifen ( 48 % ) , fulvestrant ( 16 % ) , and chemotherapy ( 68 % ) . The most common grade 3 or 4 adverse events were stomatitis ( 8 % in the everolimus-plus-exemestane group vs. 1 % in the placebo-plus-exemestane group ) , anemia ( 6 % vs. < 1 % ) , dyspnea ( 4 % vs. 1 % ) , hyperglycemia ( 4 % vs. < 1 % ) , fatigue ( 4 % vs. 1 % ) , and pneumonitis ( 3 % vs. 0 % ) . At the interim analysis , median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane , according to assessment s by local investigators ( hazard ratio for progression or death , 0.43 ; 95 % confidence interval [ CI ] , 0.35 to 0.54 ; P<0.001 ) . Median progression-free survival was 10.6 months and 4.1 months , respectively , according to central assessment ( hazard ratio , 0.36 ; 95 % CI , 0.27 to 0.47 ; P<0.001 ) . CONCLUSIONS Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors . ( Funded by Novartis ; BOLERO-2 Clinical Trials.gov number , NCT00863655 . ) Purpose Pre clinical studies demonstrate synergistic anti-tumor activity with the combination of everolimus and cisplatin . We conducted a phase I study to establish the recommended phase II of oral everolimus to be given with low-dose weekly intravenous cisplatin . Methods Part A used a st and ard 3 + 3 dose escalation scheme . There were 4 planned dose levels of everolimus : 2.5 , 5 , 7.5 , and 10 mg/day . Subjects received oral everolimus during days 1–21 and cisplatin 20 mg/m2 intravenously ( fixed dose ) on days 1 , 8 , and 15 of a 28-day cycle . Pharmacokinetic ( PK ) blood sample s were collected on day 1 and day 8 of cycle 1 in Part A. After the phase II recommended dose was established ( Part A ) , 6 additional subjects were enrolled in an expansion cohort ( Part B ) . Response was assessed by RECIST q 2 cycles for all subjects . Results Thirty patients were enrolled ( 18 male , 12 female ) and 29 were treated . Median age was 61 years ( 31–79 ) and the median number of prior cytotoxic chemotherapy regimens was 2 ( 0–3 ) . Eighty-three percent of subjects had received prior RT . DLTs occurred at dose level 1 ( sudden death of unclear cause in a patient with melanoma metastatic to liver ) and dose level 2 ( bowel obstruction ) . No DLTs occurred at dose levels 3 and 4 . The most common adverse events ( ≥ grade 3 ) among 28 patients evaluable for toxicity were lymphopenia ( 36 % ) , hyperglycemia ( 11 % ) , fatigue ( 11 % ) , and venous thrombosis ( 11 % ) . PK analysis of everolimus demonstrated dose-proportional increases in Cmax ( mean 91.9 ng/ml ) and AUC0-INF ( mean 680.5 h*ng/ml ) at dose level 4 . Three partial responses were seen ( metastatic pulmonary carcinoid , n = 2 ; metastatic sinus carcinoma , n = 1 ) . Prolonged stable disease ≥6 cycles occurred in subjects with pulmonary carcinoid , oropharyngeal squamous cell carcinoma , basal cell carcinoma , papillary thyroid carcinoma , and esthesioneuroblastoma ( n = 1 each ) . Conclusion The phase II recommended dose is everolimus 10 mg/day ( days 1–21 ) + cisplatin 20 mg/m2 ( days 1 , 8 , and 15 ) of a 28-day cycle . PK data demonstrate dose-proportional increases in exposure , as previously described for everolimus monotherapy . Anti-tumor activity was observed in several tumor types BACKGROUND Everolimus ( RAD001 ) is an orally administered inhibitor of the mammalian target of rapamycin ( mTOR ) , a therapeutic target for metastatic renal cell carcinoma . We did a phase III , r and omised , double-blind , placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy . METHODS Patients with metastatic renal cell carcinoma which had progressed on sunitinib , sorafenib , or both , were r and omly assigned in a two to one ratio to receive everolimus 10 mg once daily ( n=272 ) or placebo ( n=138 ) , in conjunction with best supportive care . R and omisation was done central ly via an interactive voice response system using a vali date d computer system , and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy , with a permuted block size of six . The primary endpoint was progression-free survival , assessed via a blinded , independent central review . The study was design ed to be terminated after 290 events of progression . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00410124 . FINDINGS All r and omised patients were included in efficacy analyses . The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed ( 101 [ 37 % ] events in the everolimus group , 90 [ 65 % ] in the placebo group ; hazard ratio 0.30 , 95 % CI 0.22 - 0.40 , p<0.0001 ; median progression-free survival 4.0 [ 95 % CI 3.7 - 5.5 ] vs 1.9 [ 1.8 - 1.9 ] months ) . Stomatitis ( 107 [ 40 % ] patients in the everolimus group vs 11 [ 8 % ] in the placebo group ) , rash ( 66 [ 25 % ] vs six [ 4 % ] ) , and fatigue ( 53 [ 20 % ] vs 22 [ 16 % ] ) were the most commonly reported adverse events , but were mostly mild or moderate in severity . Pneumonitis ( any grade ) was detected in 22 ( 8 % ) patients in the everolimus group , of whom eight had pneumonitis of grade 3 severity . INTERPRETATION Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies BACKGROUND Everolimus , an oral inhibitor of the mammalian target of rapamycin ( mTOR ) , has shown antitumour activity in patients with advanced pancreatic neuroendocrine tumours . We aim ed to assess the combination of everolimus plus octreotide long-acting repeatable ( LAR ) in patients with low- grade or intermediate- grade neuroendocrine tumours ( carcinoid ) . METHODS We did a r and omised , double-blind , placebo-controlled , phase 3 study comparing 10 mg per day oral everolimus with placebo , both in conjunction with 30 mg intramuscular octreotide LAR every 28 days . R and omisation was by interactive voice response systems . Participants were aged 18 years or older , with low- grade or intermediate- grade advanced ( unresectable locally advanced or distant metastatic ) neuroendocrine tumours , and disease progression established by radiological assessment within the past 12 months . Our primary endpoint was progression-free survival . Adjusted for two interim analyses , the prespecified boundary at final analysis was p≤0·0246 . This study is registered at Clinical Trials.gov , number NCT00412061 . FINDINGS 429 individuals were r and omly assigned to study groups ; 357 participants discontinued study treatment and one was lost to follow-up . Median progression-free survival by central review was 16·4 ( 95 % CI 13·7 - 21·2 ) months in the everolimus plus octreotide LAR group and 11·3 ( 8·4 - 14·6 ) months in the placebo plus octreotide LAR group ( hazard ratio 0·77 , 95 % CI 0·59 - 1·00 ; one-sided log-rank test p=0·026 ) . Drug-related adverse events ( everolimus plus octreotide LAR vs placebo plus octreotide LAR ) were mostly grade 1 or 2 , and adverse events of all grade s included stomatitis ( 62%vs 14 % ) , rash ( 37%vs 12 % ) , fatigue ( 31%vs 23 % ) , and diarrhoea ( 27%vs 16 % ) . INTERPRETATION Everolimus plus octreotide LAR , compared with placebo plus octreotide LAR , improved progression-free survival in patients with advanced neuroendocrine tumours associated with carcinoid syndrome . FUNDING Novartis Pharmaceuticals Everolimus downregulates glucose metabolism – associated genes in pre clinical models . Inhibition of glucose metabolism measured by 18F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non – small cell lung cancer ( NSCLC ) patients . Methods : In 8 NSCLC patients treated with everolimus , the percentage change in 18F-FDG PET uptake ( days 8 and 28 relative to baseline ) was determined using a variety of summed st and ardized uptake value ( SUV ) measures . Both maximum and mean SUVs were used , with normalizations to body surface area and body weight and with and without correcting for plasma glucose levels . Results : In 5 patients , a reduction of 18F-FDG PET uptake on day 8 was observed with all methods , ranging from −12.8 % to −72.2 % . Conclusion : These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using 18F-FDG PET There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma ( HCC ) after liver transplantation . This open , multicenter , retrospective , uncontrolled cohort study was design ed to evaluate the safety and preliminary efficacy of the combined use of a mammalian target of rapamycin ( mTOR ) inhibitor and sorafenib in this setting . In 31 patients who suffered from HCC recurrence after liver transplantation , the immunosuppressive therapy was changed to mTOR inhibitors , and systemic treatment with sorafenib was initiated . This combination was maintained until symptomatic tumor progression , death , hepatic decompensation , or unacceptable toxicity occurred . Primary treatment efficacy was determined by overall survival and progression-free survival , and secondary efficacy was determined by the overall response rate . Toxicity parameters associated with the use of sorafenib and mTOR inhibitors were also analyzed . The overall response rate according to the Response Evaluation Criteria in Solid Tumors was 3.8 % ( 1/26 ) , and there was sustained stabilization of the disease in 13 additional cases ( 50.0 % ) . The median overall survival was 19.3 months [ 95 % confidence interval ( CI ) = 13.4 - 25.1 months ] , and the median time to progression was 6.77 months ( 95 % CI = 2.3 - 11.1 months ) . Only 2 grade 3/4 cases of hyperglycemia and 1 case of grade 3/4 mucositis were reported , and they were possibly related to mTOR inhibitors . The most common severe adverse event probably related to sorafenib was diarrhea ( 12.9 % ) . In conclusion , the coadministration of sorafenib and an mTOR inhibitor could be effective despite notable toxicity in patients with post-liver transplant HCC recurrence not suitable for radical therapy . The toxicity and efficacy need to be further evaluated in r and omized controlled studies for this combination to be considered a valid option Background . Because mammalian target of rapamycin ( mTOR ) inhibitors combine anticancer and immunosuppressive properties we investigated : 1 ) the activation status and prognostic significance of the mTOR pathway in hepatocellular carcinoma ( HCC ) tissues of patients undergoing orthotopic liver transplantation ( OLT ) for HCC , and 2 ) the single and combinatorial efficacy of RAD001 in HCC cells . Methods . PTEN , p-AKT , p-mTOR , p-p70S6 K , and p-4EBP-1 were analyzed by immunohistochemistry in explanted HCCs of 166 patients undergoing OLT . Efficacy of RAD001 as mono- and combination therapy with doxorubicin was tested in Hep3B and SNU398 cells . Results . The mTOR pathway is activated in about 40 % of patients undergoing OLT for HCC but no direct correlation between up- and downstream proteins was observed . We found no influence of mTOR pathway protein expression on disease free survival ( DFS ) or overall survival ( OS ) . There was a marked single agent and chemo-sensitizing effect of RAD001 against HCC cells in vitro . Conclusion . The mTOR pathway is active in 40 % of patients with HCC undergoing OLT , but has no influence of DFS or OS . No direct correlation was observed between up- and downstream proteins limiting the use of upstream proteins to predict mTOR activity . Prospect i ve clinical trials are needed to test whether the activation status of the mTOR pathway in HCCs predicts the antitumor effect of rapamycin derivative in the posttransplantation course PURPOSE Positron emission tomography ( PET ) with [(18)F]fluorodeoxyglucose ( FDG-PET ) has increasingly been used to evaluate the efficacy of anticancer agents . We investigated the role of FDG-PET as a predictive marker for response to mammalian target of rapamycin ( mTOR ) inhibition in advanced solid tumor patients and in murine xenograft models . PATIENTS AND METHODS Thirty-four rapamycin-treated patients with assessable baseline and treatment FDG-PET and computed tomography scans were analyzed from two clinical trials . Clinical response was evaluated according to Response Evaluation Criteria in Solid Tumors , and FDG-PET response was evaluated by quantitative changes and European Organisation for Research and Treatment of Cancer ( EORTC ) criteria . Six murine xenograft tumor models were treated with temsirolimus . Small animal FDG-PET scans were performed at baseline and during treatment . The tumors were analyzed for the expression of pAkt and GLUT1 . RESULTS Fifty percent of patients with increased FDG-PET uptake and 46 % with decreased uptake had progressive disease ( PD ) . No objective response was observed . By EORTC criteria , the sensitivity of progressive metabolic disease on FDG-PET in predicting PD was 19 % . Pre clinical studies demonstrated similar findings , and FDG-PET response correlated with pAkt activation and plasma membrane GLUT1 expression . CONCLUSION FDG-PET is not predictive of proliferative response to mTOR inhibitor therapy in both clinical and pre clinical studies . Our findings suggest that mTOR inhibitors suppress the formation of mTORC2 complex , result ing in the inhibition of Akt and glycolysis independent of proliferation in a subset of tumors . Changes in FDG-PET may be a pharmacodynamic marker for Akt activation during mTOR inhibitor therapy . FDG-PET may be used to identify patients with persistent Akt activation following mTOR inhibitor therapy BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma PURPOSE To identify the optimal regimen and dosage of the oral mammalian target of rapamycin inhibitor everolimus ( RAD001 ) . METHODS We performed a dose-escalation study in advanced cancer patients administering oral everolimus 5 to 30 mg/wk , with pharmacokinetic ( PK ) and pharmacodynamic ( PD ) studies . PD data prompted investigation of 50 and 70 mg weekly and daily dosing at 5 and 10 mg . RESULTS Ninety-two patients were treated . Dose-limiting toxicity was seen in one patient each at 50 mg/wk ( stomatitis and fatigue ) and 10 mg/d ( hyperglycemia ) ; hence , the maximum-tolerated dose was not reached . S6 kinase 1 activity in peripheral-blood mononuclear cells was inhibited for at least 7 days at doses > or= 20 mg/wk . Area under the curve increased proportional to dose , but maximum serum concentration increased less than proportionally at doses > or= 20 mg/wk . Terminal half-life was 30 hours ( range , 26 to 38 hours ) . Partial responses were observed in four patients , and 12 patients remained progression free for > or= 6 months , including five of 10 patients with renal cell carcinoma . CONCLUSION Everolimus was satisfactorily tolerated at dosages up to 70 mg/wk and 10 mg/d with predictable PK . Antitumor activity and PD in tumors require further clinical investigation . Doses of 20 mg/wk and 5 mg/d are recommended as appropriate starting doses for these studies The phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin pathway plays a critical role in the pathogenesis of hepatocellular carcinoma ( HCC ) . We performed a single‐arm , phase 1/2 study of everolimus in patients with advanced HCC Posttransplant immunosuppression with calcineurin inhibitors ( CNIs ) is associated with impaired renal function , while mTor inhibitors such as everolimus may provide a renal‐sparing alternative . In this r and omized 1‐year study in patients with liver transplantation ( LTx ) , we sought to assess the effects of everolimus on glomerular filtration rate ( GFR ) after conversion from CNIs compared to continued CNI treatment . Eligible study patients received basiliximab induction , CNI with/without corticosteroids for 4 weeks post‐LTx , and were then r and omized ( if GFR > 50 mL/min ) to continued CNIs ( N = 102 ) or subsequent conversion to EVR ( N = 101 ) . Mean calculated GFR 11 months postr and omization ( ITT population ) revealed no significant difference between treatments using the Cockcroft‐Gault formula ( −2.9 mL/min in favor of EVR , 95%‐CI : [ −10.659 ; 4.814 ] , p = 0.46 ) , whereas use of the MDRD formula showed superiority for EVR ( −7.8 mL/min , 95%‐CI : [ −14.366 ; −1.191 ] , p = 0.021 ) . Rates of mortality ( EVR : 4.2 % vs. CNI : 4.1 % ) , biopsy‐proven acute rejection ( 17.7 % vs. 15.3 % ) , and efficacy failure ( 20.8 % vs. 20.4 % ) were similar . Infections , leukocytopenia , hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group . No hepatic artery thrombosis and no excess of wound healing impairment were noted . Conversion from CNI‐based to EVR‐based immunosuppression proved to be a safe alternative post‐LTx that deserves further investigation in terms of nephroprotection UNLABELLED Management of patients with hepatocellular carcinoma ( HCC ) recurrence after liver transplantation ( OLT ) is not well established . We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients . The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria , had an average follow-up of 60 months . RESULTS The median time to recurrence was 23.4 months . Surgical resection of the recurrence was possible in 11 patients , but an R-0 resection was obtained in 8 patients . Four of these 8 patients developed another recurrence , with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence . The other 4 patients without recurrences , include 3 who are alive at 19 , 31 , and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence . The 3 patients with palliative resections developed recurrences . Twelve patients were rejected for surgery : 8 were treated symptomatically , 2 with systemic chemotherapy , and 2 with everolimus and sorafenib . This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months . Of 15 patients who died , 13 succumbed to HCC recurrence . The average survival from transplantation was 61.7 + /- 37.5 and 48 + /- 34.3 months for patients without and with recurrence , respectively ( P < .001 ) . The survival from the recurrence was significantly higher among patients with R-0 surgery : 32.3 + /- 21.5 versus 11.9 + /- 6.9 months ( P = .006 ) . CONCLUSIONS HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival . Few cases are amenable to R-0 resection , but when possible it was associated with a significantly increased survival , although with an high incidence of a new recurrence . There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression , which warrants r and omized studies PURPOSE Everolimus is a selective mammalian target of rapamycin ( mTOR ) inhibitor with promising anticancer activity . In order to identify a rationally based dose and schedule for cancer treatment , we have conducted a tumor pharmacodynamic phase I study in patients with advanced solid tumors . PATIENTS AND METHODS Fifty-five patients were treated with everolimus in cohorts of 20 , 50 , and 70 mg weekly or 5 and 10 mg daily . Dose escalation depended on dose limiting toxicity ( DLT ) rate during the first 4-week period . Pre- and on-treatment steady-state tumor and skin biopsies were evaluated for total and phosphorylated ( p ) protein S6 kinase 1 , eukaryotic initiation factor 4E ( elF-4E ) binding protein 1 ( 4E-BP1 ) , eukaryotic initiation factor 4 G ( eIF-4 G ) , AKT , and Ki-67 expression . Plasma trough levels of everolimus were determined on a weekly basis before dosing during the first 4 weeks . RESULTS We observed a dose- and schedule-dependent inhibition of the mTOR pathway with a near complete inhibition of pS6 and peIF-4 G at 10 mg/d and > or= 50 mg/wk . In addition , pAKT was upregulated in 50 % of the treated tumors . In the daily schedule , there was a correlation between everolimus plasma trough concentrations and inhibition of peIF4 G and p4E-BP1 . There was good concordance of mTOR pathway inhibition between skin and tumor . Clinical benefit was observed in four patients including one patient with advanced colorectal cancer achieving a partial response . DLTs occurred in five patients : one patient at 10 mg/d ( grade 3 stomatitis ) and four patients at 70 mg/wk ( two with grade 3 stomatitis , one with grade 3 neutropenia , and one with grade 3 hyperglycemia ) . CONCLUSION Everolimus achieved mTOR signaling inhibition at doses below the DLT . A dosage of 10 mg/d or 50 mg/wk is recommended for further development |
2,317 | 25,887,973 | Although some economic modeling studies included the costs of ' asthma prevented ' , the collective literature of AIT economics provides very little to no information about the cost benefits of the preventive aspect of AIT .
SUMMARY Overall , individual studies and systematic review s provide strong evidence for the cost-effectiveness of AIT over SDT .
The magnitude of cost-efficacy is likely underestimated in that few studies consider the cost-savings due to AIT 's long-term benefits or preventive effect | PURPOSE OF REVIEW To evaluate the cost-effectiveness of allergen immunotherapy ( AIT ) in the treatment of allergic rhinitis and asthma . | BACKGROUND Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis ( ARC ) , but a lack of robust evidence has deterred its use in North America . OBJECTIVE To determine the efficacy and tolerability of st and ardized glycerinated short ragweed sublingual allergen immunotherapy liquid ( RW-SAIL ) extract in subjects with ragweed-related ARC . METHODS This phase 3 , r and omized , placebo-controlled trial was conducted in North America . Subjects ( age range , 18 - 55 years ) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed . Subjects self-administered the maximum tolerated dose of RW-SAIL ( n = 218 ) or placebo ( n = 211 ) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season . The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores ( TCS ) . RESULTS During the entire season , there was a 43 % decrease in TCS in subjects treated with RW-SAIL compared with placebo . Similar decreases were observed in TCS between the 2 groups during peak season ( 42 % ) and in daily symptom scores during the entire ( 42 % ) and peak ( 41 % ) seasons . The occurrence of adverse events was similar between the treatment groups ; most were mild in severity . Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited . No anaphylaxis occurred . CONCLUSIONS This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual st and ardized ragweed allergen immunotherapy liquid extract for the treatment of ARC BACKGROUND Data on the long-term effects of sublingual immunotherapy ( SLIT ) are sparse , and the optimal duration of treatment is a matter of debate . OBJECTIVE We sought to prospect ively evaluate the long-term effect of SLIT given for 3 , 4 , or 5 years and to compare the effect of those different duration s. METHODS In this prospect i ve open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years . The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3 , 4 , or 5 years . Clinical scores , skin sensitizations , methacholine reactivity , and nasal eosinophil counts were evaluated every year during the winter months . The clinical effect was considered to persist until clinical scores remained at less than 50 % of the baseline value , and then patients underwent another course of SLIT . RESULTS Seventy-eight patients were enrolled , and 59 completed the study . In the 12 control subjects no relevant change in clinical scores was seen throughout the study . In the patients receiving SLIT for 3 years , the clinical benefit persisted for 7 years . In those receiving immunotherapy for 4 or 5 years , the clinical benefit persisted for 8 years . New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT ( 21 % , 12 % , and 11 % , respectively ) . The second course of vaccination induced a benefit more rapidly than the first course . The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score . CONCLUSION Under the present conditions , it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination ABSTRACT Background : Concomitant allergic rhinitis ( AR ) adds to the symptomatic burden of asthma . Scope : To determine the proportion of adults with concomitant asthma and AR whose AR is diagnosed and /or treated , data were derived from a cross-sectional , stratified , r and om sample of 26,468 adults from France , Germany and the UK , participants in the 2004 web-based National Health and Wellness Survey . Patients were drawn from the data base if they reported ( 1 ) experiencing asthma in the prior 12 months , ( 2 ) a physician diagnosis of asthma , and ( 3 ) ever experiencing ‘ nasal allergies/hay fever ’ ( physician diagnosed or self-reported symptoms ) . Findings : Of 1139 patients with asthma who reported AR , 203 ( 18 % ) did not have a diagnosis of AR . Of these , 86 ( 42 % ) pursued over-the-counter self-treatment for AR , and 117 ( 58 % ) remained untreated . Of 936 patients who reported diagnosed AR , 471 ( 50 % ) received AR prescriptions , 200 ( 21 % ) pursued over-the-counter self-treatment , and 265 ( 28 % ) remained untreated . Overall , 34 % of patients with asthma and diagnosed or self-reported AR were not treated for AR . There were no significant differences in QoL over the prior 4 weeks , nor healthcare re source use over the prior 6 months between patients treated and those not treated for AR . Conclusion : Based on self-reported data , despite global treatment guidelines recommending evaluation and treatment of AR among patients with asthma , AR was not diagnosed for 1 in 5 patients , and AR was not treated for 1 in 3 patients with asthma OBJECTIVES To determine whether long-term , continuous use of inhaled anti-inflammatory medications affects asthma outcomes in children with mild to moderate asthma after use is discontinued . STUDY DESIGN Of the 1041 participants in the Childhood Asthma Management Program r and omized clinical trial , 941 ( 90 % ) were followed to determine whether 4.3 years of twice-daily budesonide or nedocromil administration ( each compared with placebo ) affected subsequent asthma outcomes during a 4.8-year posttrial period in which treatment was managed by the participants ' physicians . RESULTS The groups treated continuously during the trial with either budesonide or nedocromil did not differ from the group given placebo in terms of lung function , control of asthma , or psychological status at the end of 4.8 years of posttrial follow-up . However , the decreased mean height in the budesonide group relative to the placebo group at the end of the trial ( 1.1 cm ; P = .005 ) remained statistically significant ( 0.9 cm ; P = .01 ) after an additional 4.8 years and was more pronounced in girls ( 1.7 cm ; P = .001 ) than in boys ( 0.3 cm ; P = .49 ) . Participants in all groups used inhaled corticosteroids during 30 % of the posttrial period . CONCLUSIONS Clinical ly meaningful improvements in the control of asthma and in airway responsiveness achieved during continuous treatment with inhaled corticosteroids do not persist after continuous treatment is discontinued BACKGROUND Allergic rhinoconjunctivitis is a global health problem . Around 14 million people in Spain , France , Italy , and Austria suffer from grass pollen induced allergic rhinitis . St and ard care only provides symptoms relief , while allergen specific immunotherapy ( SIT ) treats the underlying cause of the disease . Grazax from ALK-Abelló is a new , tablet-based , effective route of SIT for home treatment . The objective was to assess the cost-effectiveness of Grazax in four Southern European countries . METHODS A prospect i ve pharmacoeconomic analyses was carried out alongside a multinational , clinical trial measuring the efficacy of Grazax . Pooled data on re source use and health outcomes were collected . A societal perspective was adopted , and the analysis had a nine-year time horizon . The primary outcome measure was quality adjusted life years ( QALYs ) . RESULTS Grazax was superior to st and ard care for all efficacy endpoints , including QALYs gained , and result ed in significantly less use of rescue medication and fewer hours missed from work . Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros . The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season . CONCLUSION The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe OBJECTIVE To investigate the health and monetary consequences of treating allergy with specific immunotherapy ( SIT ) compared with symptomatic treatment/st and ard care among patients with grass pollen or mite allergy . METHODS We performed an economic analysis based on 253 grass- and /or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit , Aarhus University Hospital and at a specialist practice in Aarhus . Relevant data were collected before , during and after SIT treatment from the national health service based on each patient 's personal identification number and medical records and from a specifically design ed question naire . A cost-benefit analysis including direct and indirect costs before , during and after SIT was performed . In addition direct costs were related to the clinical effect ( improvement in well-being ) in the form of a cost-effectiveness analysis . RESULTS The direct cost per patient/year before SIT ( equivalent to st and ard care ) was DKK 2,580 . The investment in SIT was DKK 27,545 ( in present values ) per patient over a 4-year period . After SIT the cost was reduced to DKK 1,072 per patient/year . In the long term , prospect i ve introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of improved well-being . However , when indirect costs were included in the economic evaluation SIT was shown to be net beneficial . CONCLUSION This study reveals that SIT is associated with initial re source investments and subsequent re source savings in the long term compared with st and ard care . When all consequences are measured in monetary terms , and assuming that sick days are associated with a loss of productivity , this analysis suggests that SIT increases societal welfare . This conclusion also holds if there is no loss of productivity BACKGROUND It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma . METHODS We r and omly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate ( at a dose of 88 mug twice daily ) or masked placebo for two years , followed by a one-year period without study medication . The primary outcome was the proportion of episode-free days during the observation year . RESULTS During the observation year , no significant differences were seen between the two groups in the proportion of episode-free days , the number of exacerbations , or lung function . During the treatment period , as compared with placebo use , use of the inhaled corticosteroid was associated with a greater proportion of episode-free days ( P=0.006 ) and a lower rate of exacerbations ( P<0.001 ) and of supplementary use of controller medication ( P<0.001 ) . In the inhaled-corticosteroid group , as compared with the placebo group , the mean increase in height was 1.1 cm less at 24 months ( P<0.001 ) , but by the end of the trial , the height increase was 0.7 cm less ( P=0.008 ) . During treatment , the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth , albeit temporarily and not progressively . CONCLUSIONS In preschool children at high risk for asthma , two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third , treatment-free year . These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued . ( Clinical Trials.gov number , NCT00272441 . ) BACKGROUND The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials . OBJECTIVE To investigate sustained efficacy and disease modification in a 5-year double-blind , placebo-controlled trial , including 2 years of blinded follow-up after completion of a 3-year period of treatment , with the SQ-st and ardized grass allergy immunotherapy tablet , Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU,(∗ ) ALK , Denmark ) or placebo . METHODS A r and omized , double-blind , placebo-controlled , multinational , phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis , with or without asthma , inadequately controlled by symptomatic medications . Two hundred thirty-eight participants completed the trial . End points included rhinoconjunctivitis symptom and medication scores , combined scores , asthma symptom and medication scores , quality of life , days with severe symptoms , immunologic end points , and safety parameters . RESULTS The mean rhinoconjunctivitis daily symptom score was reduced by 25 % to 36 % ( P ≤ .004 ) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial . The rhinoconjunctivitis DMS was reduced by 20 % to 45 % ( P ≤ .022 for seasons 1 - 4 ; P = .114 for season 5 ) , and the weighted rhinoconjunctivitis combined score was reduced by 27 % to 41 % ( P ≤ .003 ) in favor of active treatment . The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group , with relative differences of 49 % to 63 % ( P ≤ .0001 ) . Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response . No safety issues were identified . CONCLUSION The results confirm disease modification by SQ-st and ardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis BACKGROUND Grass pollen immunotherapy is an effective treatment for seasonal allergic rhinitis that provides the opportunity to study the induction and maintenance of allergen-specific immune tolerance . OBJECTIVES We investigated the relationship between clinical responsiveness , regulatory cytokine production , and antibody responses to allergen during 1 year of immunotherapy . METHODS Eighteen subjects with severe seasonal allergic rhinitis were r and omized double-blind to receive active or placebo injections of an alum-adsorbed grass pollen vaccine ( Alutard SQ ) . Subjects underwent repeated testing of early- and late-phase skin responses to intradermal allergen , and cellular responses to grass pollen allergen were tested . Sera were tested for allergen-specific IgG4 , IgA , and inhibitory activity in biologic assays of IgE responses . RESULTS Grass pollen immunotherapy was effective in reducing overall symptom scores ( P < .05 ) and conjunctival reactivity ( P < .05 ) . In the active group significant IL-10 production occurred early at low allergen doses and at a similar time as inhibition of late skin responses at 2 to 4 weeks . Serum allergen-specific IgG4 , IgA , and inhibitory antibody activity for basophil histamine release and IgE-facilitated allergen binding to B cells occurred later , at 6 to 12 weeks , at higher allergen doses and preceded inhibition of early skin responses . CONCLUSION IL-10 responses occur early but at immunotherapy doses that are not clinical ly effective . Later induction of inhibitory antibodies , including IgG4 and IgA , might be required for efficacy through modulation of IgE-mediated events UNLABELLED The aim of this study was to determine the extent of unawareness and undertreatment of asthma and allergic rhinitis in an adolescent and adult population in Copenhagen , Denmark . METHODS Patients with asthma and rhinitis were recruited by a st and ardised asthma and rhinitis screening question naire . Out of a r and om sample of 10,877 subjects aged 14 - 44 years , 1149 subjects were treated or reported symptoms of asthma or rhinitis and agreed to participate . Those subjects were assessed on history , lung function tests , and skin prick tests . Disease severity and optimal treatment were decided according to the GINA and ARIA guidelines . RESULTS A total of 726 participants suffered from asthma and /or allergic rhinitis . Concomitant upper and lower airways disease was found in 47 % . Seventy-five per cent were allergic and 44 % with a known allergy had been tested previously . Asthma was undiagnosed and untreated in 50 % of all the asthmatics . According to the guideline recommendation , 76 % of asthmatics were undertreated . Rhinitis was undiagnosed in 32 % of patients and 83 % with moderate to severe rhinitis were undertreated . Patient knowledge about self-care and education was low . CONCLUSIONS In this population a large proportion of patients were unaware of having asthma or rhinitis . The pharmaceutical treatment and management practice were inadequate . Our study emphasises the need for additional intervention BACKGROUND The worldwide increased prevalence of allergic diseases , and especially of respiratory allergy , is paralleled by increased health costs . This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice . OBJECTIVE To compare the different economic relevance , over a long evaluation time , of symptomatic pharmacologic therapy and sublingual immunotherapy ( SLIT ) in patients with allergic asthma . METHODS Seventy patients with perennial allergic asthma , sensitized to dust mites , were enrolled ; 50 of these patients were treated with SLIT against house dust mites and 20 were treated with symptomatic drugs . The patients were evaluated for 2 years after discontinuing immunotherapy , which was performed for 3 years , to obtain a more complete follow-up . Symptom scores , medication scores , and all other direct medical costs were evaluated with a specific question naire . RESULTS Patients treated with SLIT plus drugs had a higher mean annual cost in the first year of SLIT treatment compared with patients only receiving drug treatment , but the mean annual cost became significantly lower since the end of SLIT both in the whole population and in the subgroups defined by disease severity . CONCLUSION The economic advantage measured alongside this prospect i ve observational study was long lasting and still present at the fifth year of the follow-up ( 2 years after discontinuing SLIT ) and could positively be related to the persistent good clinical control of patients BACKGROUND Sublingual allergen immunotherapy ( SLIT ) is a commonly used alternative route of administration to st and ard subcutaneous immunotherapy ( SCIT ) in Europe . Despite its wide use , the cost-effectiveness of SLIT vs SCIT has not been well established . OBJECTIVE To evaluate the cost and effectiveness of SLIT compared with SCIT in patients with allergic rhinoconjunctivitis during a 3-year specific allergen immunotherapy ( SIT ) from a third-party payer 's , a patient 's , and society 's perspectives . METHODS We performed an open-label r and omized clinical trial of patients receiving SLIT ( n = 19 ) , patients receiving SCIT ( n = 23 ) , and a control group ( n = 22 ) . The outcome measures were Rhinoconjunctivitis Quality of Life Question naire score , visual analog scale score , symptomatic medication reduction , and direct and indirect costs . RESULTS SLIT offered clinical benefits to patients comparable to those provided by SCIT . From the perspective of a third-party payer , the total average direct medical cost per patient of 3-year SIT was estimated at Euro 416 vs Euro 482 in the SLIT and SCIT groups , respectively . A patient who received SLIT paid less than a patient who received SCIT for all out-of-pocket costs ( Euro176 for SLIT vs Euro 255 for SCIT ) but more for sole allergen extracts ( Euro 72 for SLIT vs Euro 55 for SCIT ) . When both direct and indirect costs were considered , the 3-year SIT expenditures per patient reached Euro 684 vs Euro 1,004 in the SLIT and SCIT groups , respectively . CONCLUSIONS SLIT represents a less expensive alternative relative to subcutaneous administration from all perspectives . However , from a patient 's perspective , SCIT offers a less expensive alternative for patients who do not experience loss of income and travel costs associated with treatment BACKGROUND The perceptions of patients and physicians regarding the symptoms and impact of allergic rhinitis ( AR ) were assessed in a prospect i ve , cross-sectional , international survey . This paper presents the combined survey results from five European countries ( Germany , France , Italy , Spain and the UK ) . METHODS Data were recorded by 1,482 patients and matched with records from 415 primary care physicians and specialists . Diagnostic tests to confirm AR had been performed on 1,279 ( 86.3 % ) patients . Both physicians and patients recorded the presence , severity and impact of symptoms at the time of consultation in addition to those symptoms frequently , but not currently , present . Health-related quality of life ( HRQoL ) was assessed using the Mini Rhinoconjunctivitis Quality of Life Question naire . RESULTS A large proportion of patients had moderate-severe disease ( 67.2 % ; n = 996 ) , persistent disease ( 42.5 % ; n = 630 ) and comorbidities such as asthma ( 31.5 % ; n = 467 ) . Overall , patients rated their disease as more severe than did physicians ( P < 0.001 ) . At the time of the consultation , one-third of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature . According to the physicians ' assessment , good control of nasal and ocular symptoms was achieved in 45.4 % ( n = 673 ) and 51.3 % ( n = 760 ) of patients , respectively , and poor symptom control in 18.0 % ( n = 267 ) and 12.1 % ( n = 179 ) . Overall , 43.3 % ( n = 641 ) of those surveyed were using two or more medicines for their AR . Health-related quality of life was correlated with disease severity and with the number of days without symptoms in the previous 4 weeks . Allergic rhinitis had a significantly greater impact in patients with more persistent disease than in those with intermittent disease ( 2.3 + /- 1.3 vs 1.9 + /- 1.2 ; P < 0.001 ) . Nonetheless , 81.8 % ( n = 601 ) of patients with intermittent disease reported some impairment of their daily life as a result of their AR . CONCLUSIONS Allergic rhinitis remains a significant health problem because of the high burden of symptoms and its impact on general well being and HRQoL among patients consulting for this condition . Overall , there was a poor correlation between patients and physicians in the reporting of disease severity |
2,318 | 17,100,960 | No differences in survival were observed .
: In patients with unresectable pancreatic cancer , NCPB is associated with improved pain control , and reduced narcotic usage and constipation compared with st and ard treatment , albeit with minimal clinical significance | BACKGROUND : A major focus of palliation in patients with unresectable pancreatic cancer is pain control .
The aim of this systematic review was to examine the efficacy and safety of neurolytic celiac plexus blockade ( NCPB ) compared with st and ard treatment in r and omized controlled trials ( RCTs ) involving patients with unresectable pancreatic cancer . | OBJECTIVE This additional analysis of data from a previously reported prospect i ve trial comparing the effect of intraoperative alcohol or saline placebo neurolytic block in patients with pancreatic cancer was conducted in response to the development of a new theory , which explores the relationship of negative mood states to pain , pain-related behavior , and ultimately , longevity . METHODS The original study used a double-blind procedure to r and omly assign 139 patients with histologically proven , unresectable pancreatic cancer to receive either an alcohol or a saline block . Data on visual analog pain , mood , and interference with activity were collected preoperatively and every 2 months postoperatively until death . The current analysis was conducted on the complete data sets received from 130 patients . Demographic data were su bmi tted to chi-square analysis and to univariate and multivariate analysis of variance . Univariate and multivariate analyses of variance also compared 1 ) the effect of alcohol versus saline on pain , mood , interference of pain with activities , and longevity and 2 ) the impact of mood on pain with longevity as the dependent variable . Correlation and regression analyses examined the impact of mood on life expectancy . RESULTS The alcohol intervention had a significant positive effect on life duration and mood scores . High negative mood states correlated significantly with an increase in visual analog pain , the rating of pain intensity at its worse , and pain interference with patients ' activities . CONCLUSION In these subjects , the neurolytic block , as compared with medical management alone , improved pain , elevated mood , reduced pain interference with activity , and was associated with an increase in life expectancy Twenty-one patients with pancreatic cancer pain were studied to evaluate the effectiveness of celiac plexus block ( CPB ) on pain relief and quality of life ( QOL ) , compared to the traditional NSAID-morphine treatment . The criteria were morphine consumption , visual analogue pain scale ( VAS ) , performance status ( PS ) determined by medical and nursing staffs , and answers to QOL question naires . Morphine consumption , VAS , PS , and self-assessed QOL scores were taken when the administration of morphine was necessary for pain relief and those scores were used as control . Morphine consumption and the VAS score were recorded at regular weekly intervals and the PS and QOL scores were measured every 2 weeks thereafter . CPB was performed within 2 - 3 days after the control measurement . The VAS scores of the patients receiving CPB ( n = 10 ) were statistically lower for the first 4 weeks after the procedure than those of the patients receiving the st and ard NSAID-morphine treatment ( n = 11 ) during the same time period after the control measurement . Morphine consumption was significantly lower in weeks 4 - 7 ( inclusive ) following the procedure in the CPB group and continued to be lower thereafter , though not significantly so . Although the PS score slightly improved at the 2nd week after CPB , it was not improved by the start of the NSAID-morphine treatment . Self-assessed QOL scores did not ameliorate statistically after CPB ; however , they did deteriorate remarkably in the patients treated only with morphine-NSAID during their survival periods , while they deteriorated only slightly in the CPB group . There were fewer side effects after CPB . These results indicate CPB does not directly improve QOL in patients with pancreatic cancer pain , but it may prevent deterioration in QOL by the long-lasting analgesic effect , limitation of side effects and the reduction of morphine consumption , compared to treatment only with NSAID-morphine CONTEXT Pancreatic cancer is an aggressive tumor associated with high mortality . Optimal pain control may improve quality of life ( QOL ) for these patients . OBJECTIVE To test the hypothesis that neurolytic celiac plexus block ( NCPB ) vs opioids alone improves pain relief , QOL , and survival in patients with unresectable pancreatic cancer . DESIGN , SETTING , AND PATIENTS Double-blind , r and omized clinical trial conducted at Mayo Clinic , Rochester , Minn. Enrolled ( October 1997 and January 2001 ) were 100 eligible patients with unresectable pancreatic cancer experiencing pain . Patients were followed up for at least 1 year or until death . INTERVENTION Patients were r and omly assigned to receive either NCPB or systemic analgesic therapy alone with a sham injection . All patients could receive additional opioids managed by a clinician blinded to the treatment assignment . MAIN OUTCOME MEASURES Pain intensity ( 0 - 10 numerical rating scale ) , QOL , opioid consumption and related adverse effects , and survival time were assessed weekly by a blinded observer . RESULTS Mean ( SD ) baseline pain was 4.4 ( 1.7 ) for NCPB vs 4.1 ( 1.8 ) for opioids alone . The first week after r and omization , pain intensity and QOL scores were improved ( pain intensity , P < or = .01 for both groups ; QOL , P<.001 for both groups ) , with a larger decrease in pain for the NCPB group ( P = .005 ) . From repeated measures analysis , pain was also lower for NCPB over time ( P = .01 ) . However , opioid consumption ( P = .93 ) , frequency of opioid adverse effects ( all P>.10 ) , and QOL ( P = .46 ) were not significantly different between groups . In the first 6 weeks , fewer NCPB patients reported moderate or severe pain ( pain intensity rating of > or = 5/10 ) vs opioid-only patients ( 14 % vs 40 % , P = .005 ) . At 1 year , 16 % of NCPB patients and 6 % of opioid-only patients were alive . However , survival did not differ significantly between groups ( P = .26 , proportional hazards regression ) . CONCLUSION Although NCPB improves pain relief in patients with pancreatic cancer vs optimized systemic analgesic therapy alone , it does not affect QOL or survival OBJECTIVE : Computed tomography (CT)-guided celiac plexus neurolysis has been used for controlling the chronic abdominal pain associated with intra-abdominal malignancy and chronic pancreatitis . Endoscopic ultrasound (EUS)-guided celiac plexus neurolysis has been reported to have some success in controlling pain from pancreatic cancer . The aim of this study is to assess the efficacy of EUS-guided celiac plexus block versus CT-guided celiac plexus block for controlling the chronic abdominal pain associated with chronic pancreatitis . METHODS : Patients enrolled were r and omly assigned to EUS-guided or CT-guided celiac plexus block . Pain scores were determined pre- and postceliac block for both techniques . Follow-up was obtained by a nurse at 1 day postblock , then weekly thereafter for 24 wk . Patients also rated overall experience with these procedures . The EUS celiac block was performed with a 22-gauge sterile needle inserted into the celiac region with guidance of real-time linear array endosonography followed by injection of 10 ml of bupivacaine ( 0.75 % ) and 3 ml ( 40 mg ) of triamcinolone on both sides of the celiac area . RESULTS : Twenty-two consecutive patients ( 10 men , 12 women ) , were ultimately enrolled in this study between 7/1/95 and 12/30/95 ; four patients were excluded for protocol violations . We performed EUS-guided celiac block in 10 patients and CT-guided celiac block in eight . A significant improvement in pain scores with reduction in pain medication usage occurred in 50 % ( five of 10 ) of patients having the EUS block . The mean postprocedure follow-up was 15 weeks ( range : 8–24 wk ) . Persistent benefit was experienced by 40 % of patients at 8 wk and by 30 % at 24 wk . In the patients with CT block , however , only 25 % ( two of eight ) had relief . The mean follow-up was 4 wk ( range : 2–6 wk ) . Only 12 % ( one of eight ) had some relief at 12 wk of follow-up . There were no complications . EUS-guided celiac block was the preferred technique among patients who experienced both techniques . A cost comparison between both celiac block techniques shows EUS to be less costly than CT . CONCLUSIONS : EUS-guided celiac block provided more persistent pain relief than CT-guided block and was the preferred technique among the subjects studied . EUS-guided celiac block appears to be a safe , effective , and less costly method for controlling the abdominal pain that can accompany chronic pancreatitis in some patients This large-volume , single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head , neck , uncinate process , body , or tail of the pancreas . Between January 1984 and July 1999 inclusive , 616 patients with adenocarcinoma of the pancreas underwent surgical resection . A retrospective analysis of a prospect ively collected data base was performed . Both univariate and multivariate models were used to determine the factors influencing survival . Of the 616 patients , 526 ( 85 % ) underwent pancreaticoduodenectomy for adenocarcinoma of the head , neck , or uncinate process of the pancreas , 52 ( 9 % ) underwent distal pancreatectomy for adenocarcinoma of the body or tail , and 38 ( 6 % ) underwent total pancreatectomy for adenocarcinoma extensively involving the gl and . The mean age of the patients was 64.3 years , with 54 % being male and 91 % being white . The overall perioperative mortality rate was 2.3 % , whereas the incidence of postoperative complications was 30 % . The median postoperative length of stay was 11 days . The mean tumor diameter was 3.2 cm , with 72 % of patients having positive lymph nodes , 30 % having positive resection margins , and 36 % having poorly differentiated tumors . Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors ( 4.7 vs. 3.1 cm , P < 0.0001 ) , but fewer node-positive resections ( 59 % vs. 73 % , P = 0.03 ) and fewer poorly differentiated tumors ( 29 % vs. 36 % , P<0.001 ) , as compared to those undergoing pancreaticoduodenectomy for right-sided lesions . The overall survival of the entire cohort was 63 % at 1 year and 17 % at 5 years , with a median survival of 17 months . For right-sided lesions the 1- and 5-year survival rates were 64 % and 17 % , respectively , compared to 50 % and 15 % for left-sided lesions . Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins ( hazard ratio [ HR ] = 0.64 , confidence interval [ CI ] = 0.50 to 0.82 , P = 0.0004 ) , tumor diameter less than 3 cm ( HR = 0.72 , CI = 0.57 to 0.90 , P = 0.004 ) , estimated blood loss less than 750 ml ( HR = 0.75 , CI = 0.58 to 0.96 , P = 0.02 ) , well/moderate tumor differentiation ( HR = 0.71 , CI = 0.56 to 0.90 , P = 0.005 ) , and postoperative chemoradiation ( HR = 0.50 , CI = 0.39 to 0.64 , P } < 0.0001 ) . Tumor location in head , neck , or uncinate process approached significance in the final multivariate model ( HR = 0.60 , CI = 0.35 to 1.0 , P = 0.06 ) . Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas . Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators . Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status The purpose of this study was to evaluate the technical possibilities of placing a catheter near the celiac plexus for performance of a celiac plexus block , and to study the efficacy of repeated neurolytic celiac plexus blocks with alcohol in patients with advanced pancreatic cancer pain resistant to opioid treatment . In 12 patients , a neurolytic celiac plexus block with alcohol , administered via an indwelling celiac catheter , was performed . To evaluate the efficacy , visual analog scale scores were recorded every day . Quality of life scores were registered before and 4 weeks following the procedure . Alterations in opioid consumption , and the time between the diagnosis of pancreatic cancer and the performance of the block , were registered . All patients were followed until they died . Two patients remained without pain after the first neurolytic celiac plexus block . In all other patients a second block was administered which provided only temporary relief . Additional intermittent administration of bupivacaine through the catheter was necessary to provide adequate pain relief in these patients . Quality of life increased significantly during the treatment . Opioid consumption decreased significantly in all patients . Our study indicates that a neurolytic celiac plexus blockade with alcohol results in a significant but short-lasting analgesic effect . The use of a celiac catheter improves the long-term management of pancreatic cancer pain OBJECTIVE A prospect i ve , r and omized , double-blind study was completed comparing intraoperative chemical splanchnicectomy with 50 % alcohol versus a placebo injection of saline in patients with histologically proven unresectable pancreatic cancer . METHODS St and ardized assessment of pain , mood , and disability due to pain was completed preoperatively and at 2-month intervals until death . Chemical splanchnicectomy with alcohol was performed in 65 patients , whereas 72 patients received the placebo . The two groups were similar with respect to age , sex , location , and stage of tumor , operation performed , the use of postoperative chemo- and radiation therapy , and initial assessment scores for pain , mood , and disability . RESULTS No differences in hospital mortality or complications , return to oral intake , or length of hospital stay were observed . Mean pain scores were significantly lower in the alcohol group at 2- , 4- , and 6-month follow-up and at the final assessment ( p < 0.05 ) . To further determine the effect of chemical splanchnicectomy , patients were stratified into those with and without preoperative pain . In patients without preoperative pain , alcohol significantly reduced pain scores and delayed or prevented the subsequent onset of pain ( p < 0.05 ) . In patients with significant preoperative pain , alcohol significantly reduced existing pain ( p < 0.05 ) . Furthermore , patients with preexisting pain who received alcohol showed a significant improvement in survival when compared with controls ( p < 0.0001 ) . CONCLUSION The results suggest that intraoperative chemical splanchnicectomy with alcohol significantly reduces or prevents pain in patients with unresectable pancreatic cancer & NA ; Neurolytic sympathetic plexus block ( NSPB ) has been proposed to prevent the development of pain and improve the quality of life of patients with cancer , thus question ing the WHO protocol that proposes the use of invasive methods only as a final resort . This study evaluates the pain relief , opioid consumption and quality of life provided by the use of NSPB in two different phases of cancer pain and compares them with that provided by pharmacological therapy only . Sixty patients with abdominal or pelvic cancer pain were divided into three groups and observed for 8 weeks . In group I , neurolytic celiac ( NCPB ) or superior hypogastric plexus block ( SHPB ) , or lumbar sympathetic ganglion chain block ( LSGCB ) was performed with alcohol in patients using NSAID and a weak oral opioid or morphine ( dose≤90 mg/day ) and reporting VAS≥4 . In group II , NCPB , SHPB or LSGCB were performed on patients using NSAID and morphine ( dose≥90 mg/day ) and reporting VAS≥4 . The patients of group III received pharmacological therapy only . The patients of groups I and II had a significant reduction of pain ( P<0.004 ) , opioid consumption ( P<0.02 ) and a better quality of life ( P<0.006 ) than those of group III , but no significant differences between groups I and II were seen in these aspects . Opioid‐related adverse effects were significantly greater in group III ( P<0.05 ) . The occasional neurolysis‐related complications were transitory . The results suggest NSPB for the management of cancer pain should be considered earlier in the disease In a r and omized double‐blind study the efficacy of neurolytic coeliac plexus block ( NCPB ) was compared with pharmacological therapy in the treatment of pain from pancreatic cancer |
2,319 | 29,438,672 | A systematic review of iTBS studies revealed variability in reliability of effects though most were in the theorized direction .
TBS protocol s appear to be effective in modulating prefrontal cortical excitability in previously theorized directions .
HIGHLIGHTSPrefrontal cTBS has a significant attenuating effect on executive functions .
The cognitive effects of prefrontal iTBS are mostly in the theorized direction .
These data suggest that TBS is a reliable means of modulating prefrontal activity | ABSTRACT Theta burst stimulation ( TBS ) is a highly efficient repetitive transcranial magnetic stimulation ( rTMS ) variant employed in experimental and clinical treatment paradigms .
Despite widespread usage of TBS targeting the prefrontal cortex ( PFC ) , there has been no systematic review of the evidence linking TBS protocol s to changes in task performance on common measures of prefrontal function in general , and executive functions specifically . | The development of stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework . A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents compete . The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity . Assuming an appropriate nonlinear form for this dependence , development of selectivity is obtained under quite general conditions on the sensory environment . One does not require nonlinearity of the neuron 's integrative power nor does one need to assume any particular form for intracortical circuitry . This is first illustrated in simple cases , e.g. , when the environment consists of only two different stimuli presented alternately in a r and om manner . The following formal statement then holds : the state of the system converges with probability 1 to points of maximum selectivity in the state space . We next consider the problem of early development of orientation selectivity and binocular interaction in primary visual cortex . Giving the environment an appropriate form , we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys . Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data . Experiments are suggested that could test our theory further Young ( ages 18 - 22 years ) and older ( ages 61 - 87 years ) adults ( N = 106 ) played the Virtual Week board game , which involves simulating common prospect i ve memory ( PM ) tasks of everyday life ( e.g. , taking medication ) , and performed working memory ( WM ) and vigilance tasks . The Virtual Week game includes regular ( repeated ) and irregular ( nonrepeated ) PM tasks with cues that are either more or less focal to other ongoing activities . Age differences in PM were reduced for repeated tasks , and performance improved over the course of the week , suggesting retrieval was more spontaneous or habitual . Correlations with WM within each age group were reduced for PM tasks that had more regular or focal cues . WM ( but not vigilance ) ability was a strong predictor of irregular PM tasks with less focal cues . Taken together , these results support the hypothesis that habitual and focally cued PM tasks are less dem and ing of attentional re sources ( specifically , WM ) , whereas tasks that are more dem and ing of controlled attentional processes produce larger age differences , which may be attributable to individual differences in WM Background : Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex ( DLPFC ) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing . However , the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be eluci date d. Objective : In this sham-controlled study in healthy individuals , we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation ( iTBS ) on reward responsiveness , as well as the influence of trait hedonic capacity . Methods : We used a r and omized crossover single session iTBS design with an interval of 1 week . We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity ( the ability to experience pleasure ) with the temporal experience of pleasure scale question naire . Results : As expected , the participants developed a response bias toward the most rewarded stimulus ( rich stimulus ) . Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus ( lean stimulus ) . Active or sham stimulation did not seem to influence the outcome . However , when taking into account individual trait hedonic capacity , we found an early significant increase in the response bias only after active iTBS . The higher the individual 's trait hedonic capacity , the more the response bias toward the rich stimulus increased after the active stimulation . Conclusion : When taking into account trait hedonic capacity , one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity . This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system This individual differences study examined the separability of three often postulated executive functions-mental set shifting ( " Shifting " ) , information updating and monitoring ( " Updating " ) , and inhibition of prepotent responses ("Inhibition")- and their roles in complex " frontal lobe " or " executive " tasks . One hundred thirty-seven college students performed a set of relatively simple experimental tasks that are considered to predominantly tap each target executive function as well as a set of frequently used executive tasks : the Wisconsin Card Sorting Test ( WCST ) , Tower of Hanoi ( TOH ) , r and om number generation ( RNG ) , operation span , and dual tasking . Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another , but are clearly separable . Moreover , structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks . Specifically , WCST performance was related most strongly to Shifting , TOH to Inhibition , RNG to Inhibition and Updating , and operation span to Updating . Dual task performance was not related to any of the three target functions . These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to study ing the organization and roles of executive functions Prospect i ve memory ( PM ) refers to a complex cognitive ability that underpins the delayed execution of previously formulated intentions . PM performance declines early in normal aging and this process is accentuated in Alzheimer 's disease . The left frontopolar cortex ( BA10 ) has been consistently assigned a major role in PM functioning , but whether it can be noninvasively modulated to enhance PM performance in aged people has not been addressed so far . Here , we investigated the effects of modulating left BA10 by means of theta burst stimulation ( TBS ) , using either excitatory ( intermittent TBS ) , inhibitory ( continuous TBS ) or control ( vertex ) TBS in healthy aged subjects . The behavioral effects were assessed using a reliable and ecological virtual reality PM task that included both event- and time-based retrievals . As compared with vertex stimulation , event-based PM performance significantly improved after excitatory stimulation , whereas inhibitory stimulation had no significant effect . Additionally , and across the different types of stimulation , performance for congruent links between the event-based PM cue and the action to be performed was significantly better as compared with incongruent links . In conclusion , intermittent TBS might provide a relevant interventional strategy to counteract the decline of cognitive functions and memory abilities in normal aging Dopamine is implicated in movement , learning , and motivation , and in illnesses such as Parkinson 's disease , schizophrenia , and drug addiction . Little is known about the control of dopamine release in humans , but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures . Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex in healthy human subjects . Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal cau date nucleus compared with rTMS of the left occipital cortex . There were no changes in binding in the putamen , nucleus accumbens , or right cau date . This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral cau date nucleus . This finding has implication s for the therapeutic and research use of rTMS in neurological and psychiatric disorders It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 The present study aim ed to investigate the role of frontopolar cortex in prospect i ve memory ( PM ) by means of inhibitory theta-burst stimulation ( cTBS ) . " Experiment 1"-8 volunteers were evaluated after inhibitory cTBS over left Brodmann area ( BA ) 10 , right BA10 , and Cz . In the PM procedure , sequences of 4 words each were presented . During the intersequence delay , subjects had to repeat the sequence in the observed order ( ongoing task forward ) or in the reverse order ( backward ) . At the occurrence of a target word , subjects had to press a key on the keyboard ( PM task ) . Recall and recognition of the target words were also tested . PM accuracy was lower after cTBS over left BA10 compared with Cz ( P = 0.012 ) , whereas it was comparable in right BA10 and Cz conditions . No other significant differences between the 3 conditions were found . " Experiment 2"-8 subjects were administered the same experimental PM procedure as above after inhibitory cTBS over left BA46 and Cz . In this case , none of the tested effects were significant . Our findings corroborate the hypothesis that within the prefrontal cortex , the left BA10 is specifically involved in the mediation of processes related to the execution of delayed intentions The involvement of frontopolar cortex in mediating prospect i ve memory processes has been evidence d by various studies , mainly by means of neuroimaging techniques . Recently , one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area ( BA ) 10 impaired verbal prospect i ve memory . This result raises the issue of whether the BA 10 involvement in prospect i ve memory functioning may be modulated by the physical characteristics of the stimuli used . The present study aim ed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation . Twelve volunteers were evaluated after inhibitory theta-burst stimulation over left BA 10 , right BA10 and CZ ( control condition ) . In the prospect i ve memory procedure , sequences of four spatial positions ( black squares ) each were presented . During the inter-sequence delay , subjects had to reproduce the sequence in the observed order ( ongoing task forward ) or the reverse order ( backward ) . At the occurrence of a target position , subjects had to press a key on the keyboard ( prospect i ve memory score ) . Recall and recognition of the target positions were also tested . We found that prospect i ve memory accuracy was lower after theta-burst stimulation over right BA10 than CZ ( p<0.01 ) , whereas it was comparable in left BA10 and CZ conditions . No significant difference was found among the three conditions on recall and recognition of target positions and on ongoing task performance . Our findings provide a novel strong evidence for a specific involvement of right frontopolar cortex in visual-spatial prospect i ve memory . In the context of previous data providing evidence for left BA 10 involvement in verbal prospect i ve memory , our results also suggest material -specific lateralization of prospect i ve memory processes in BA 10 Although previous studies have shown that the rostral prefrontal cortex ( rPFC ) plays a crucial role in executive tasks , the various functions of the rPFC in the humans are still understudied . Here we used transcranial magnetic stimulation ( TMS ) with continuous theta burst stimulation ( cTBS ) to interfere with the executive control functions of the right rostrolateral PFC ( RLPFC ) or the right rostromedial PFC ( RMPFC ) . Subjects performed a task-switching paradigm , which included spatial detection ( SD ) , prospect i ve memory ( PM ) and working memory ( WM ) tasks , after cTBS . The performance of 18 healthy volunteers was evaluated on different days after cTBS over the right RLPFC , the right RMPFC , and the vertex ( serving as a control site ) . The application of cTBS over the RLPFC significantly increased the switching costs ( SCs ) of the error rates ( ERs ) when switching to the PM task , while RMPFC-cTBS decreased SCs of ERs when switching to the WM task , compared with the control vertex site . These findings provide evidence for a differential role of the RLPFC and the RMPFC in executive functions , with a specific involvement of the RLPFC and the RMPFC in PM , and WM , respectively The brain-derived neurotrophic factor gene ( BDNF ) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism ( BDNF Val66Met ) in the normal population that is associated with differences in hippocampal volume and episodic memory . It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task . Here we extend these studies by using new non-invasive transcranial magnetic stimulation ( TMS ) and transcranial direct current stimulation ( TDCS ) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest . We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism . Val66Met carriers were matched with Val66Val individuals and tested on the following protocol s : continuous and intermittent theta burst TMS ; median nerve paired associative stimulation ; and homeostatic plasticity in the TDCS/1 Hz rTMS model . The response of Met allele carriers differed significantly in all protocol s compared with the response of Val66Val individuals . We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD . The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke . Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence , presumably concurrent with anatomical brain maturational changes . The relatively scarce developmental functional imaging literature on cognitive control , however , has been inconsistent with respect to the neurofunctional substrates of this cognitive development , finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood . Such inconsistencies may be due to small subject numbers or confounds from age-related performance differences in block design functional MRI ( fMRI ) . In this study , rapid , r and omized , mixed-trial event-related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults . Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition ( Go/no-go task ) , cognitive interference inhibition ( Simon task ) , and attentional set shifting ( Switch task ) . Adults compared with children showed increased brain activation in task-specific frontostriatal networks , including right orbital and mesial prefrontal cortex and cau date during the Go/no-go task , right mesial and inferior prefrontal cortex , parietal lobe , and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task . Whole-brain regression analyses with age across all subjects showed progressive age-related changes in similar and extended clusters of task-specific frontostriatal , frontotemporal , and frontoparietal networks . The findings suggest progressive maturation of task-specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid-adulthood Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ( $ 11-$80 ) available immediately and larger rewards ( $ 25-$85 ) available after delays ranging from 1 week to 6 months . Participants had a 1-in-6 chance of winning a reward that they chose on one r and omly selected trial . Delay-discounting rates were estimated from the pattern of participants ' choices . The discounting model of impulsiveness ( Ainslie , 1975 ) implies that delay-discounting rates are positively correlated with impulsiveness . On average , heroin addicts ' discount rates were twice those of controls ( p = .004 ) , and discount rates were positively correlated with impulsivity as measured by self-report question naires ( p < .05 ) . The results lend external validity to the delay-discounting rate as a measure of impulsiveness , a characteristic associated with substance abuse This study investigated time-based prospect i ve memory ( PM ) performance in 76 younger and 76 older adults with a time-monitoring task in which participants were required to press a design ated key every 5 minutes while watching a movie . Participants were assigned to two conditions , free and fixed monitoring . In free monitoring participants could check a clock when they wanted , but in fixed monitoring they were restricted a maximum of six times every 5 minutes . We also investigated the involvement of time perception , inhibition , and updating in time-based PM performance . We hypothesised that participants with inefficiencies in those three cognitive functions would have less strategic monitoring behaviour and would also be less accurate at the target time . In the free-monitoring condition older adults checked the clock more frequently than younger participants , but presented with a similar pattern of monitoring behaviour and increased their frequency of clock checking closer to the target time . In the fixed-monitoring condition younger participants checked the clock more frequently than older adults and showed a strategic pattern of monitoring . Older adults did not show strategic use of clock checking and their monitoring function remained unchanged . Differences in PM accuracy and monitoring behaviour are discussed according to different involvement of cognitive abilities Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation ( rTMS ) exerts antidepressant effects , the neurobiological action of rTMS in patients with depression is poorly understood . Pre clinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions . We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [ 123I ] iodobenzamide ( IBZM ) single photon emission computed tomography ( SPECT ) approach . Five patients with a major depressive episode ( DSM-IV ) underwent an acute 10 Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [ 123I ] IBZM-SPECT bolus and constant infusion protocol . In four subjects the protocol was repeated after a three week rTMS st and ard treatment . Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest ( ROI ) technique . The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine . Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2 % in IBZM binding to striatal dopamine D2 receptors after rTMS challenge compared to baseline ( p=0.01 , Wilcoxon test ) . In this preliminary study , the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS . In future , this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission BACKGROUND Because st and ard repetitive transcranial magnetic stimulation ( rTMS ) protocol s exhibit post-stimulus effects of short duration , novel protocol s such as theta burst stimulation ( TBS ) , are promising approaches to enhance the effectiveness of rTMS . However , little is known about the side effect profile of such protocol s. Thus , the present study explores whether TBS is safe particularly in terms of effects on cognition , mood , and electroencephalogram ( EEG ) measures in healthy subjects . METHODS Twenty-four healthy volunteers participated in 2 r and omized , placebo-controlled , cross-over experiments and underwent continuous TBS ( cTBS ) , intermittent TBS ( iTBS ) , and shamTBS either over the left dorsolateral prefrontal cortex ( DLPFC , n = 12 ) or the medial prefrontal cortices ( mPFC , n = 12 ) . Clinical side effects , performance in a neuropsychological battery , mood changes , and resting EEG were recorded . RESULTS Neither a seizure nor epileptiform EEG activity was observed . The most prominent side effect was the occurrence of vagal reactions during TBS ; otherwise no serious side effects were found . St and ardized low-resolution brain electromagnetic tomography showed current density changes in the alpha2 b and after iTBS of the DLPFC , which remained detectable up to 50 min after stimulation . The few changes in neuropsychological performance were concordant with stimulation site . No impact on mood was detected . CONCLUSIONS Although TBS protocol s of the human prefrontal cortex seem to be safe in healthy subjects , future studies need to address the occurrence of vagal reactions . Excitatory and inhibitory properties of motor cortex TBS might not be transferable to prefrontal sites , and the action of specific TBS protocol s needs to be further investigated prior to clinical application Objectives Prior research has demonstrated that executive function ( EF ) strength is positively associated with dietary self-control . As such , the differential operation of the brain centers underlying EFs ( i.e. , dorsolateral prefrontal cortex [ DLPFC ] ) may explain controlled aspects of dietary self-control . The present study was design ed to examine the causal relationship between DLPFC function and two aspects of dietary self-control : visceral cravings and actual consumptive behaviors . Methods The research was conducted using a within-participant design . A sample of 21 healthy female young adults aged 19 to 26 years ( mean [ M ; st and ard deviation ] = 21.10 [ 1.86 ] years ) received both active and sham continuous theta burst stimulation ( cTBS ) to the left DLPFC . Before and after each session , subjective food cravings were assessed using the Food Craving Question naire — State . After each stimulation session , participants competed three measures of EF ( Stroop , Go/No-Go , and Stop-Signal ) and a bogus taste test . Results Participants reported larger increases in snack food cravings after active stimulation ( M = 9.98 % change , st and ard error [ SE ] = 0.45 ) than after sham stimulation ( M = −3.46 , SE = 0.39 , p = .012 ) on the reinforcement anticipation dimension of Food Craving Question naire — State . Likewise , participants consumed significantly more snack foods after active stimulation ( M = 70.62 grams , SE = 5.17 ) than after sham stimulation ( M = 61.33 , SE = 3.56 , p = .006 ) . Finally , performance on the Stroop task was reduced more after active ( M = 71.56 milliseconds , SE = 25.18 ) than after sham stimulation ( M = 20.16 , SE = 13.32 , p = .033 ) ; reduction in Stroop performance mediated the effect of active stimulation on increased appetitive food consumption . Conclusion These results support the contention that EF strength , as modulated by DLPFC activity , is causally associated with effective dietary self-control This study investigated the role of processing speed and working memory in prospect i ve and retrospective memory ( i.e. , free recall ) performance within old age . The aim was to examine age-related differences in both memory domains within the age range of 65 to 80 years . The sample consisted of 361 older adults from Wave 1 data of the Zurich Longitudinal Study on Cognitive Aging . Using structural equation modeling , prospect i ve memory , free recall , working memory , and processing speed were identified as latent constructs . Age effects were found to be larger for prospect i ve memory than for free recall . Furthermore , when controlling for individual differences in working memory and processing speed , unique age effects remained for prospect i ve , but not retrospective , memory performance . Results indicate that , within old age , prospect i ve memory represents a distinct memory construct that is partially independent of age-related individual differences in speed of processing , working memory , and retrospective memory |
2,320 | 29,967,603 | Conclusion PAI-1 is a significant predictor of disease severity and all-cause mortality in sepsis . | Objectives Plasminogen activator inhibitor-1 ( PAI-1 ) , a crucial regulator of fibrinolysis , is increased in sepsis , but its values in predicting disease severity or mortality outcomes have been controversial .
Therefore , we conducted a systematic review and meta- analysis of its predictive values in sepsis . | This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Objective To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinical ly defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient 's status . The following measurements were undertaken : Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , multiple organ failure ( MOF ) score , plasma levels of thrombin — antithrombin III complexes ( TAT ) , antithrombin III ( AT III ) , protein C antigen , factor XII , and plasminogen activator inhibitor type 1 antigen ( PAI-1 ) , neopterin , and interleukin 6 ( IL-6 ) . Design A prospect i ve case series study . Setting Intensive care unit ( ICU ) of the Department of Internal Medicine , Justus Liebig University , Giessen , Germany . Patients 28 consecutive patients ( 11 females , 17 males ; mean age 58 years ) with clinical ly defined sepsis . Eleven patients were admitted from the surgical ICU ( 9 after elective surgery , 2 after trauma surgery ) . The operations were done 1–26 days ( mean 14 days ) prior to the onset of sepsis . Main results At the onset of sepsis we found elevated plasma levels of TAT , PAI-1 , neopterin , and IL-6 , and lowered plasma levels of AT III , factor XII , and protein Cantigen . Neopterin , PAI-1 , IL-6 , and factor XII showed a statistically significant correlation with the APACHE II score . The MOF score is significantly correlated with IL-6 and neopterin . The extent of hemostatic abnormalities was related to increasing levels of IL-6 . Conclusions Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system , the vascular endothelium , and the monocyte/macrophage system . IL-6 may have a regulatory function for hemostasis in inflammation . Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis Variables of the fibrinolytic system were prospect ively studied in patients with haematologic malignancies in chemotherapy-induced leukocytopenia at onset and during the course of septicemia to evaluate their prognostic value . This group of patients was chosen because of their high risk of developing severe septic complications , thus allowing serial prospect i ve testing of fibrinolytic variables prior to and during evolving sepsis or septic shock . 62 patients with febrile infectious events were accrued to the study . Of these , 13 patients progressed to severe sepsis and an additional 13 patients to septic shock as defined according to st and ard diagnostic criteria . At onset of fever , plasminogen activator inhibitor ( PAI ) activity and PAI-1 antigen levels increased from normal baseline levels and were significantly higher in the group of patients who developed septic shock compared to those with severe sepsis ( medians : 10.6 versus 1.3 U/ml , p = 0.0001 ; 50.0 versus 5.0 ng/ml , p = 0.0002 ) . The increase in PAI activity and antigen in septic shock was accompanied by an increase in tissue-type plasminogen activator antigen and total fibrin(ogen ) degradation products and a decrease in alpha(2)-antiplasmin activity ( p < 0.006 ) . In contrast , in the group of patients that developed severe sepsis the variables of the fibrinolytic system remained unchanged at onset of fever . These differences between septic shock and severe sepsis were sustained throughout the septic episode for all variables ( p < 0.0001 ) . PAI activity of > 5 U/ml at onset of fever predicted a lethal outcome with a sensitivity of 92 % and a specificity of 100 % . Thus , septic shock in leukocytopenia is associated with significant activation of the fibrinolytic system presumably as a response of the vascular endothelium to inflammatory injury . Furthermore , PAI activity measurements are sensitive markers of an unfavourable prognosis Circulating levels of thrombin-antithrombin III complex ( TAT ) and plasmin-α2 plasmin inhibitor complex ( PIC ) in 49 septic patients ( 23 patients with organ dysfunction ( OD ) , 26 without OD ) and 11 postgastrectomy patients were measured to determine the significance of the coagulation-fibrinolytic systems in the development of OD . Tissue plasminogen activator ( t-PA ) , plasminogen activator inhibitor 1 ( PAI-1 ) , and thrombomodulin were also measured . The mean level of TAT on the day when OD occurred was significantly higher compared with the maximum level of TAT in septic patients without OD ( P < .01 ) or postoperative patients ( P < .01 ) . There was no difference in PIC levels between the three groups . The TAT/PIC ratio was significantly higher in septic patients with OD compared with the other groups ( P < .001 ) . Septic patients with OD showed higher levels of PAI-1 ( P < .001 ) but not of t-PA . Thrombomodulin levels were significantly higher in the septic patients with OD compared with the others ( P < .001 ) . We conclude that suppression of the fibrinolytic system contributes to the imbalance between coagulation and fibrinolysis , and that this hypercoagulabe millieu on the endothelial surface leads to the onset of OD Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome . Early identification of this condition could be of interest . The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality . Methods This single center observational prospect i ve pilot study was performed in an adult Intensive Care Unit ( ICU ) of a tertiary academic hospital . Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included . Forty healthy individuals served as controls . We modified conventional kaolin activated thromboelastography ( TEG ) adding urokinase to improve assessment of fibrinolysis in real time ( UK-TEG ) . TEG , UK-TEG , plasminogen activator inhibitor (PAI)-1 , thrombin-activatable fibrinolysis inhibitor ( TAFI ) , d-dimer , DIC scores and morbidity ( rated with the SOFA score ) were measured upon ICU admission . Logistic regression was used to calculate odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CIs ) of mortality at ICU discharge . Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1 . TAFI was not different between sepsis patients and healthy individuals . 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score ( 8 ( 6–13 ) vs 5 ( 4–7 ) , p = 0.03 ) , higher mortality ( 39 % vs 5 % , p = 0.01 ) and greater markers of cellular damage ( lactate levels , LDH and bilirubin ) . Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 ( % ) parameter ( OR 0.95 , 95 % CI 0.93–0.98 , p = 0.003 ) . Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage , morbidity and mortality Introduction Current criteria for early diagnosis of coagulopathy in sepsis are limited . We postulated that coagulopathy is already complicated with sepsis in the initial phase , and severe coagulopathy or disseminated intravascular coagulation ( DIC ) becomes overt after progressive consumption of platelet and coagulation factors . To determine early diagnostic markers for severe coagulopathy , we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis . Methods A single-center , prospect i ve observational study was conducted in an adult ICU at a university hospital . Plasma sample s were obtained from patients with sepsis at ICU admission . Fourteen biomarkers including global markers ( platelet count , prothrombin time , activated partial thromboplastin time , fibrinogen and fibrin degradation product ( FDP ) ) ; markers of thrombin generation ( thrombin-antithrombin complex ( TAT ) and soluble fibrin ) ; markers of anticoagulants ( protein C ( PC ) and antithrombin ) ; markers of fibrinolysis ( plasminogen , α2-plasmin inhibitor ( PI ) , plasmin-α2-PI complex , and plasminogen activator inhibitor (PAI)-1 ) ; and a marker of endothelial activation ( soluble E-selectin ) were assayed . Patients who had overt DIC at baseline were excluded , and the remaining patients were followed for development of overt DIC in 5 days , and for mortality in 28 days . Results A total of 77 patients were enrolled , and 37 developed overt DIC within the following 5 days . Most patients demonstrated hemostatic abnormalities at baseline with 98.7 % TAT , 97.4 % FDP and 88.3 % PC . Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC . Notably , TAT , PAI-1 and PC discriminated well between patients with and without developing overt DIC ( area under the receiver operating characteristic curve ( AUROC ) , 0.77 ( 95 % confidence interval , 0.64 to 0.86 ) ; 0.87 ( 0.78 to 0.92 ) ; 0.85 ( 0.76 to 0.91 ) , respectively ) , and using the three together , significantly improved the AUROC up to 0.95 ( vs. TAT , PAI-1 , and PC ) . Among the significant diagnostic markers for overt DIC , TAT and PAI-1 were also good predictors of 28-day mortality ( AUROC , 0.77 and 0.81 , respectively ) . Conclusions Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC . A single measurement of TAT , PAI-1 , and PC activity could identify patients with ongoing severe coagulopathy , early in the course of sepsis Introduction Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis . We investigated the association between biomarkers of endothelial cell activation and sepsis severity , organ dysfunction sequential organ failure assessment ( SOFA ) score , and death . Methods This is a prospect i ve , observational study including adult patients ( age 18 years or older ) presenting with clinical suspicion of infection to the emergency department ( ED ) of an urban , academic medical center between February 2005 and November 2008 . Blood was sample d during the ED visit and biomarkers of endothelial cell activation , namely soluble fms-like tyrosine kinase-1 ( sFlt-1 ) , plasminogen activator inhibitors -1 ( PAI-1 ) , sE-selectin , soluble intercellular adhesion molecule ( sICAM-1 ) , and soluble vascular cell adhesion molecule ( sVCAM-1 ) , were assayed . The association between biomarkers and the outcomes of sepsis severity , organ dysfunction , and in-hospital mortality were analyzed . Results A total of 221 patients were included : sepsis without organ dysfunction was present in 32 % , severe sepsis without shock in 30 % , septic shock in 32 % , and 6 % were non-infected control ED patients . There was a relationship between all target biomarkers ( sFlt-1 , PAI-1 , sE-selectin , sICAM-1 , and sVCAM-1 ) and sepsis severity , P < 0.05 . We found a significant inter-correlation between all biomarkers , including the strongest correlations between sFlt-1 and sE-selectin ( r = 0.55 , P < 0.001 ) , and between sFlt-1 and PAI-1 ( 0.56 , P < 0.001 ) . Among the endothelial cell activation biomarkers , sFlt-1 had the strongest association with SOFA score ( r = 0.66 , P < 0.001 ) , the highest area under the receiver operator characteristic curve for severe sepsis of 0.82 , and for mortality of 0.91 . Conclusions Markers of endothelial cell activation are associated with sepsis severity , organ dysfunction and mortality . An improved underst and ing of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis Genetic variants of hemostatic factors leading to prothrombotic phenotypes of hypercoagulability and hypofibrinolysis might affect prognosis of septic critically ill patients . Our aim was to evaluate the effect of four hemostatic genetic variants , namely fibrinogen-β-455G/A , factor XIII ( FXIII ) V34L , plasminogen activator inhibitor-1 ( PAI-1 ) 4G/5 G polymorphisms and factor V Leiden ( FVL ) mutation on survival of critically ill patients with severe sepsis or septic shock . A prospect i ve , observational study in an 18-bed general ICU included 73 patients with severe sepsis or septic shock . Epidemiological , laboratory data and comorbidities along with severity scores were recorded . Genotyping for fibrinogen-β-455G/A , FXIII V34L and PAI-1 4G/5 G polymorphism and FVL mutation was carried out in all patients . The primary outcomes were the 28-day and the 90-day survival . Age , septic shock , severity indexes , prior steroid use and arterial pH were identified as predictors of the 28-day and 90-day survival in both the univariate and the multivariate models . On the contrary , none of the examined polymorphisms was found to significantly affect either the 28-day or the 90-day survival . Our data suggest that the importance of these hemostatic polymorphisms as predictors of the prognosis of sepsis in critically ill patients is probably very small Purpose Pentraxin 3 ( PTX3 ) is an inflammatory mediator produced by neutrophils , macrophages , myeloid dendritic and endothelial cells . During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur . PTX3 , as a mediator of inflammation , may represent an early marker of severity and outcome in sepsis . Methods This study is based on a prospect i ve trial regarding the impact of glycemic control on coagulation in sepsis . Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed . At enrollment , we recorded sepsis signs , disease severity , coagulation activation [ prothrombin fragments 1 + 2 ( F1 + 2 ) ] and fibrinolysis inhibition [ plasminogen activator inhibitor-1 ( PAI-1 ) ] . We measured plasma PTX3 levels at enrollment , everyday until day 7 , then at days 9 , 11 , 13 , 18 , 23 and 28 . Mortality was recorded at day 90 . Results Although not different on day 1 , PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days ( p = 0.002 by general linear model ) . On day 1 , PTX3 levels were higher in septic shock than in severely septic patients ( p = 0.029 ) . Day 1 PTX3 was significantly correlated with platelet count ( p < 0.001 ) , SAPS II score ( p = 0.006 ) and SOFA score ( p < 0.001 ) . Day 1 PTX3 was correlated with F1 + 2 concentration and with PAI-1 activity and concentration ( p < 0.05 for all ) . Conclusions Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality . PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction Plasminogen activator inhibitor-1 ( PAI-1 ) is a member of the serine protease inhibitor ( serpin ) supergene family and a central regulatory protein in the blood coagulation system . PAI-1 is unique among serpins in exhibiting distinct active and inactive ( latent ) conformations in vivo . Though the structure of latent PAI-1 was recently solved , the structure of the short-lived , active form of PAI-1 is not known . In order to probe the structural basis for this unique conformational change , a r and omly mutated recombinant PAI-1 expression library was constructed in bacteriophage and screened for increased functional stability . Fourteen unique clones were selected , and shown to exhibit functional half-lives ( T1/2S ) exceeding that of wild-type PAI-1 by up to 72-fold . The most stable variant ( T1/2 = 145 h ) contained four mutations . Detailed analysis of these four mutations , individually and in combination , demonstrated that the markedly enhanced functional stability of the parent compound mutant required contributions from all four substitutions , with no individual T1/2 exceeding 6.6 h. The functional stability of at least eight of the remaining 13 compound mutants also required interactions between two or more amino acid substitutions , with no single variant increasing the T1/2 by > 10-fold . The nature of the identified mutations implies that the unique instability of the PAI-1 active conformation evolved through global changes in protein packing and suggest a selective advantage for transient inhibitor function Purpose SuPAR ( soluble urokinase plasminogen activator receptor ) and PAI-1 ( plasminogen activator inhibitor 1 ) are active in the coagulation-fibrinolysis pathway . Both have been suggested as biomarkers for disease severity . We evaluated them in prediction of mortality , acute lung injury (ALI)/acute respiratory distress syndrome ( ARDS ) , sepsis and renal replacement therapy ( RRT ) in operative and non-operative ventilated patients . Methods We conducted a prospect i ve , multicenter , observational study . Blood sample s and data of intensive care were collected . Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis , and healthy volunteers were analysed for comparison . Receiver operating characteristics ( ROC ) , logistic regression , likelihood ratios and Kaplan – Meier analysis were performed . Results Baseline suPAR was 11.6 ng/ml ( quartiles Q1–Q3 , 9.6–14.0 ) , compared to healthy volunteers with suPAR of 0.6 ng/ml ( 0.5–11.0 ) . PAI-1 concentrations were 2.67 ng/ml ( 1.53–4.69 ) and 0.3 ng/ml ( 0.3–0.4 ) , respectively . ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves ( AUC ) 0.61 ( 95 % confidence interval ( CI ) : 0.55–0.67 ) , sepsis 0.68 ( 0.61–0.76 ) , ALI/ARDS 0.64 ( 0.56–0.73 ) and RRT 0.65 ( 0.56–0.73 ) . Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 ( 1.37–4.64 , p = 0.003 ) for 90-day mortality and 3.16 ( 1.19–8.41 , p = 0.02 ) for ALI/ARDS . In non-operative patients , the AUC ’s for suPAR were 90-day mortality 0.61 ( 0.54–0.68 ) , RRT 0.73 ( 0.64–0.83 ) , sepsis 0.70 ( 0.60–0.80 ) , ALI/ARDS 0.61 ( 0.51–0.71 ) . Predictive value of PAI-1 was negligible . Conclusions In non-operative patients , low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality . SuPAR may be used for screening for patients with potentially good survival . The association with RRT may supply an early warning sign for acute renal failure Severe sepsis and septic shock are major causes of morbidity and mortality among children in pediatric intensive care units ( PICUs ) worldwide . Activated protein C ( PC ) is a critical endogenous regulator of coagulation and inflammation in patients with sepsis . However , the role of PC in pediatric sepsis is still obscure . We prospect ively recruited infants and children aged between 1 month and 15 years old who were admitted to PICU with a clinical diagnosis of systemic inflammatory response syndrome , sepsis , or septic shock . Clinical data were recorded and blood sample s kept for further analysis . We then measured the levels of PC activity . Of the approximately 1,100 pediatric patients admitted to PICU from January 1 , 2004 to December 31 , 2005 , 75 were diagnosed with septic shock ( 6.8 % ) , and 67 sample s were available for analysis . Out of these , 41 ( 61 % ) were survivors , and 26 ( 39 % ) were nonsurvivors . The average plasma PC activity ( % ) was at 37.8 ± 4.4 . Plasma PC activity ( % ) was significantly lower in the nonsurvivors compared with the survivors at 23.6 ± 4.3 and 46.8 ± 6.3 ( P = 0.002 ) , respectively . D-Dimer levels were not significantly different between the survivors ( 1,461 ± 266 ng/mL ) and the nonsurvivors ( 1,989 ± 489 ng/mL ) ( P = 0.68 ) . Also , there was no correlation between plasma PC activity and D-dimer levels ( r = −0.07 ; P = 0.6 ) . Importantly , the odds of dying were significantly higher in patients whose level of PC activity was less than 25 % ( odds ratio = 5.6 ; P = 0.02 ) . Pediatric patients with septic shock demonstrate very low levels of PC activity , and this may be associated with an increased risk of death . Abbreviations-PICU-pediatric intensive care unit ; rhAPC-Recombinant human activated protein C ; APC-Activated protein C ; PC-Protein C ; PRISM-score Pediatric risk of mortality score ; SIRS- Systematic inflammatory response syndrome ; PCR-Polymerase chain reaction ; PT-Prothrombin time ; PTT-Partial thromboplastin time ; iCa-ionized OBJECTIVE Disseminated intravascular coagulation ( DIC ) is often associated with infection and a poor outcome . In this study , useful markers for predicting poor outcomes were examined . METHODS The frequency of DIC and organ failure , outcomes and hemostatic markers were prospect ively evaluated in 242 patients with infections . RESULTS Seventy-seven patients were diagnosed with DIC , 36 of whom recovered from the condition . The rate of DIC or resolution of DIC was highest in the patients with sepsis and lowest in the patients with respiratory infections . Mortality tended to be high in the patients with respiratory infections . The DIC score , sepsis-related organ failure assessment ( SOFA ) score , prothrombin time ( PT ) ratio and thrombin-antithrombin complex level were significantly high in the patients who did not recover from DIC . The age , DIC score , SOFA score , PT ratio and levels of thrombomodulin and plasminogen activator inhibitor (PAI)-I were significantly high in the non-survivors . Factors related to a poor outcome included resolution of DIC , the SOFA score , age and the PT ratio . Factors related to resolution of DIC included the SOFA score and age , while factors related to the SOFA score included the levels of PAI-I , leukocytes , fibrinogen , D-dimer and platelets . CONCLUSION The outcomes of septic patients primarily depend on the SOFA score and the resolution of DIC , which are related to organ failure Previous studies found increased circulating levels of biomarkers related to endothelial cell activation in patients with sepsis , particularly in the most severe sepsis stages of sepsis shock . It remains unclear , however , whether this activation is mainly driven by sepsis-specific mechanisms or occurs as a generalized inflammatory response . The objective of this analysis was to compare patterns of biomarkers of endothelial cell activation in patients with hypotension due to sepsis and nonsepsis etiologies . This is a secondary analysis of a prospect i ve , observational cohort study including emergency department patients older than17 years with an episode of hypotension defined as any systolic blood pressure measurement less than 100 mmHg . Etiology of hypotension episodes was classified as sepsis or nonsepsis ( eg , cardiac or hemorrhagic ) . Endothelial activation biomarkers of cell adhesion ( E-selectin , vascular cell adhesion molecule 1 [ VCAM-1 ] , and intercellular adhesion molecule 1 [ ICAM-1 ] ) , coagulation ( plasminogen activator inhibitor 1 [ PAI-1 ] ) , and vascular endothelial growth factor ( VEGF ) signaling ( VEGF , soluble fms-like tyrosine kinase 1 [ sFLT-1 ] ) were assayed . A total of 161 patients were analyzed . Hypotension was classified as sepsis ( n = 69 ) , nonsepsis ( cardiac [ n = 35 ] , hemorrhagic [ n = 12 ] ) , or indeterminate ( n = 45 ) . With the exception of PAI-1 , median plasma levels of all endothelial markers were significantly higher in patients with sepsis compared with nonsepsis etiology ( P < 0.05 for all comparisons ) . Logistic regression analysis , adjusted for age , sex , mean blood pressure level , and mortality , confirmed a significant association of E-selectin ( odds ratio [ OR ] , 3.7 ; 95 % confidence interval [ CI ] , 1.7 - 7.8 , P < 0.001 ) and sFLT-1 ( OR , 2.0 ; CI , 1.1 - 3.8 ; P < 0.03 ) with sepsis etiology . Biomarkers VCAM-1 ( OR , 2.0 ; CI , 0.88 - 4.4 ; P = 0.1 ) , VEGF ( OR , 1.5 ; CI , 0.98 - 2.2 ; P = 0.06 ) , ICAM-1 ( OR , 1.5 ; CI , 0.9 - 2.6 ; P = 0.2 ) , and PAI-1 ( OR , 1.4 ; CI , 0.8 - 2.3 ; P = 0.2 ) did not reach statistical significance . This study found a sepsis-specific activation of endothelium activation markers , particularly E-selectin and sFLT-1 , in emergency department patients with hypotension . ABBREVIATIONS-ED-emergency department ; ICAM-1-soluble intercellular adhesion molecule 1 ; PAI-1-plasminogen activator inhibitor 1 ; sFLT-1-soluble fms-like tyrosine kinase 1 ; VCAM-1-soluble vascular cell adhesion molecule 1 ; VEGF-vascular endothelial growth BACKGROUND Higher plasma plasminogen activator inhibitor-1 ( PAI-1 ) levels have been reported in septic patients . However , some questions remain unanswered , such as whether there is an association between plasma PAI-1 levels and sepsis severity and mortality , and inflammation state during the first week . METHODS Multicenter , observational and prospect i ve study carried out in six Spanish Intensive Care Units of 260 patients with severe sepsis . Circulating levels of PAI-1 and tumour necrosis factor (TNF)-α were measured at day 1 , 4 and 8 . End-point was 30-day mortality . RESULTS Nonsurviving septic patients ( n=89 ) presented higher PAI-1 levels than surviving ( n=171 ) at day 1 ( 58.4 ( 33.3 - 83.8 ) vs 36.5 ( 21.1 - 62.5 ) ng/mL ; p<0.001 ) , 4 ( 34.0 ( 14.7 - 53.3 ) vs 16.2 ( 10.2 - 27.4 ) ng/mL ; p<0.001 ) and 8 ( 30.6 ( 16.2 - 47.8 ) vs 18.9 ( 10.4 - 29.5 ) ng/mL ; p=0.004 ) . We found a positive correlation of PAI-1 levels with SOFA , lactic acid , aPTT , INR and TNF-α , and negative with platelet count at day 1 , 4 and 8 . Logistic regression analyses showed that PAI-1 levels at day 1 ( p<0.001 ) , 4 ( p<0.001 ) and 8 ( p=0.001 ) were associated with 30-day mortality . On ROC curve analysis to predict 30- day survival , the area under the curve of PAI-1 levels at day 1 , 4 and 8 were 0.65 ( 95 % CI=0.58 - 0.72 ; p<0.001 ) , 0.69 ( 95 % CI=0.60 - 0.78 ; p<0.001 ) and 0.65 ( 95 % CI=0.54 - 0.75 ; p=0.005 ) respectively . CONCLUSIONS The most interesting findings of our study , to our knowledge the largest series reporting PAI-1 levels during follow-up in septic patients , were that plasma PAI-1 levels during the first week were associated with inflammation , severity and mortality OBJECTIVE To determine the involvement of coagulation in bleeding and poor outcome in patients with severe leptospirosis . METHODS In a prospect i ve study , parameters of the coagulation system were measured on admission and during follow-up in 52 consecutive patients with severe leptospirosis . RESULTS All patients showed coagulation disorders , such as prolonged prothrombin time ( PT ) and activated partial thromboplastin time , marked procoagulant activity [ thrombin-antithrombin ( TAT ) complexes , prothrombin fragment 1 + 2 , D-dimer ] , reduced levels of anticoagulant markers ( protein C , antithrombin ) and increased ( anti- ) fibrinolytic activity [ plasmin-antiplasmin ( PAP ) complexes , plasminogen activator inhibitor-1 ] . These disorders were more pronounced in patients who died eventually . PT prolongation was associated with mortality ( OR 1.4 , 95 % CI : 1.0 - 1.8 , P = 0.04 ) . Bleeding occurred in 31 subjects ( 60 % ) . Of these , 24 had mild bleeding and seven had severe haemorrhages . Thrombocytopenia ( platelets < /=100 x 10(9)/l ) was significantly associated with clinical bleeding ( OR 4.6 , 95 % CI : 1.3 - 16 ) . A sub analysis of patients with and without severe bleeding revealed a more pronounced imbalance of the coagulation system in patients with severe bleeding , as reflected by a significant association with PT ( OR 1.4 , 95 % CI : 1.0 - 1.8 , P = 0.05 ) and the TAT/PAP ratio ( OR 1.3 , 95 % CI : 1.0 - 1.6 , P = 0.05 ) , which is an indicator of the balance between coagulation and fibrinolysis . Overt disseminated intravascular coagulation ( DIC ) was found in 10 ( 22 % ) of the 46 patients for whom the score could be calculated . There was no significant association between DIC scores , bleeding diathesis or poor outcome . CONCLUSION The coagulation system was strongly activated in patients with leptospirosis . This was more pronounced in the deceased and in patients with severe bleeding than in than the survivors and in those without severe bleeding |
2,321 | 30,487,973 | Conclusions and limitations The association between treatment for diabetes and dementia is differential according to drug class , which is potentially mediated by hypoglycemic risk . | Background The association between diabetes mellitus ( DM ) treatment and dementia is not well understood .
Objective To investigate the association between treatment of diabetes , hypoglycemia , and dementia risk . | Objectives Possible association between diabetes mellitus ( DM ) and Alzheimer ’s disease ( AD ) has been controversial . This study used a nationwide population -based data set to investigate the relationship between DM and subsequent AD incidence . Methods Data were collected from Taiwan ’s National Health Insurance Research Data base , which released a cohort data set of 1,000,000 r and omly sample d people and confirmed it to be representative of the Taiwanese population . We identified 71,433 patients newly diagnosed with diabetes ( age 58.74±14.02 years ) since January 1997 . Using propensity score , we matched them with 71,311 non-diabetic subjects by time of enrollment , age , gender , hypertension , hyperlipidemia , and previous stroke history . All the patients were followed up to December 31 , 2007 . The endpoint of the study was occurrence of AD . Results Over a maximum 11 years of follow-up , diabetic patients experienced a higher incidence of AD than non-diabetic subjects ( 0.48 % vs. 0.37 % , p<0.001 ) . After Cox proportional hazard regression model analysis , DM ( hazard ratio [ HR ] , 1.76 ; 95 % confidence interval [ CI ] , 1.50–2.07 , p<0.001 ) , age ( HR , 1.11 ; 95 % CI , 1.10–1.12 , p<0.001 ) , female gender ( HR , 1.24 ; 95 % CI , 1.06–1.46 , p = 0.008 ) , hypertension ( HR , 1.30 ; 95 % CI , 1.07–1.59 , p = 0.01 ) , previous stroke history ( HR , 1.79 ; 95 % CI , 1.28–2.50 , p<0.001 ) , and urbanization status ( metropolis , HR , 1.32 ; 95 % CI , 1.07–1.63 , p = 0.009 ) were independently associated with the increased risk of AD . Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis . However , combination therapy with insulin was found to be associated with greater risk of AD ( HR , 2.17 ; 95 % CI , 1.04–4.52 , p = 0.039 ) . Conclusion Newly diagnosed DM was associated with increased risk of AD . Use of hypoglycemic agents did not ameliorate the risk OBJECTIVE To investigate the associations of metformin , serum vitamin B12 , calcium supplements , and cognitive impairment in patients with diabetes . RESEARCH DESIGN AND METHODS Participants were recruited from the Primary Research in Memory ( PRIME ) clinics study , the Australian Imaging , Biomarkers and Lifestyle ( AIBL ) study of aging , and the Barwon region of southeastern Australia . Patients with Alzheimer disease ( AD ) ( n = 480 ) or mild cognitive impairment ( n = 187 ) and those who were cognitively intact ( n = 687 ) were included ; patients with stroke or with neurodegenerative diseases other than AD were excluded . Subgroup analyses were performed for participants who had either type 2 diabetes ( n = 104 ) or impaired glucose tolerance ( n = 22 ) . RESULTS Participants with diabetes ( n = 126 ) had worse cognitive performance than participants who did not have diabetes ( n = 1,228 ; adjusted odds ratio 1.51 [ 95 % CI 1.03–2.21 ] ) . Among participants with diabetes , worse cognitive performance was associated with metformin use ( 2.23 [ 1.05–4.75 ] ) . After adjusting for age , sex , level of education , history of depression , serum vitamin B12 , and metformin use , participants with diabetes who were taking calcium supplements had better cognitive performance ( 0.41 [ 0.19–0.92 ] ) . CONCLUSIONS Metformin use was associated with impaired cognitive performance . Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes . Prospect i ve trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin Background : Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer ’s disease dementia ( AD ) or amnestic mild cognitive impairment ( MCI ) . The investigation of longer-term administration is necessary to determine whether benefits persist , whether they are similar to benefits provided by regular insulin , and whether either form of insulin therapy affects AD biomarkers . Objective : The present study aim ed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition , daily functioning , and AD biomarkers for adults with MCI or AD . Methods : This r and omized , double-blind , placebo-controlled trial included an intent-to-treat sample consisting of 36 adults diagnosed with MCI or mild to moderate AD . Participants received placebo ( n = 12 ) , 40 IU of insulin detemir ( n = 12 ) , or 40 IU of regular insulin ( n = 12 ) daily for four months , administered with a nasal delivery device . A cognitive battery was administered at baseline and after two and four months of treatment . MRI was administered for all participants and lumbar puncture for a subset ( n = 20 ) at baseline and four months . The primary outcome was change from baseline to four months on a memory composite ( sum of Z scores for delayed list and story recall ) . Secondary outcomes included : global cognition ( Alzheimer ’s Disease Assessment Scale-Cognition ) , daily functioning ( Dementia Severity Rating Scale ) , MRI volume changes in AD-related regions of interest , and cerebrospinal fluid AD markers . Results : The regular insulin treated group had better memory after two and four months compared with placebo ( p < 0.03 ) . No significant effects were observed for the detemir-assigned group compared with the placebo group , or for daily functioning for either group . Regular insulin treatment was associated with preserved volume on MRI . Regular insulin treatment was also associated with reduction in the tau-P181/Aβ42 ratio . Conclusion : Future research is warranted to examine the mechanistic basis of treatment differences , and to further assess the efficacy and safety of intranasal insulin Diabetes mellitus is a leading cause of death in the United States and is associated with microvascular and macrovascular complications . Approximately 29.1 million persons , or 9.3 % of the U.S. population , have type 2 diabetes ( 1 ) . In 2012 , the total direct and indirect costs associated with diabetes in the United States were $ 245 billion ( 1 ) . Markedly elevated glucose levels can result in subacute symptoms , such as polyuria , polydipsia , weight loss , and dehydration . Over time , the metabolic derangements associated with diabetes may lead to vision loss , painful neuropathy or sensory loss , foot ulcers , amputations , myocardial infa rct ions , strokes , and end-stage renal disease . Lowering blood glucose may decrease risk for complications , but lowering strategies come with harms , patient burden , and costs . Blood glucose can be measured in various ways , including the hemoglobin A1c ( HbA1c ; also called glycosylated or glycated hemoglobin ) level , which approximates average blood glucose control over about 3 months . As with all laboratory tests , HbA1c measurements are associated with variability ( 2 ) and can vary further with race and ethnicity ( 35 ) . Guidelines have historically recommended initiation or intensification of pharmacologic therapy to achieve specific HbA1c targets , depending on the population in question . The ideal target that optimally balances benefits and harms remains uncertain . Guidance Statement Focus and Target Population The purpose of this American College of Physicians ( ACP ) guidance statement is to critically review the available guidelines from various organizations and the evidence included therein to assist clinicians in making decisions about targets when using pharmacologic therapy in adults with type 2 diabetes . Recent data suggesting that newer agents reduce cardiovascular morbidity and mortality in high-risk patients with type 2 diabetes have prompted calls for a fundamental shift in diabetes management . Some anticipate that treatment decisions will eventually be based more on cardiovascular risk than achievement of specific HbA1c targets , analogous to recent changes in lipid management . However , for the foreseeable future , glycemic targets will continue to influence management decisions by front-line clinicians ( 6 ) . This statement focuses on the benefits and harms of targeting lower versus higher HbA1c levels and does not cover use of specific medications outside of their use to achieve HbA1c targets . The intended audience is all clinicians , and the target population is nonpregnant adults with type 2 diabetes . Methods The Clinical Guidelines Committee ( CGC ) of ACP develops guidance statements on topics where several conflicting guidelines are available . We provide clinicians with a rigorous review of the guidelines and the evidence they include . We then adopt the clinical recommendations if we agree with their evaluation of benefits and harms or adapt them if changes are needed based on our assessment of the recommendations and evidence . Data Sources and Guideline Selection We search ed the National Guideline Clearinghouse and the Guidelines International Network library ( May 2017 ) for guidelines on recommended HbA1c targets in the treatment of type 2 diabetes in nonpregnant outpatient adults . We included guidelines that were developed by national organizations , were published in English , and targeted the correct population . We review ed titles and abstract s and excluded guidelines that were modified or adapted from other organizations or addressed specific population s ( such as pregnant women or patients with kidney disease ) . Our search yielded guidelines from the National Institute for Health and Care Excellence ( NICE ) ( 7 ) and the Institute for Clinical Systems Improvement ( ICSI ) ( 8) . On the basis of the knowledge and expertise of ACP CGC members , we also selected the following 4 guidelines not identified in either data base at the time of the search but commonly used in clinical practice : the American Association of Clinical Endocrinologists and American College of Endocrinology ( AACE/ACE ) guideline ( 9 ) , the American Diabetes Association ( ADA ) guideline ( 10 ) , the Scottish Intercollegiate Guidelines Network ( SIGN ) guideline ( 11 ) , and the U.S. Department of Veterans Affairs and Department of Defense ( VA/DoD ) guideline ( 12 ) . Quality Assessment Six co authors independently review ed and assessed each guideline using the AGREE II ( Appraisal of Guidelines for Research and Evaluation II ) instrument ( 13 ) . This instrument asks 23 questions in the following 6 domains : scope and purpose , stakeholder involvement , rigor of development , clarity of presentation , applicability , and editorial independence . The authors scored each guideline independently , and the scores were compared ( Appendix Figure and Appendix Table 1 ) . Authors then provided a summary determination of whether they would recommend this guideline for use by recording yes , no , or yes with modifications . Appendix Figure . Mean AGREE II scores for items in each domain across the 6 review ers . Each question was rated on a Likert scale with a minimum of 1 point and a maximum of 7 points . The scores were averaged for each of the 6 review ers . Error bars represent calculated st and ard deviation . AACE/ACE = American Association of Clinical Endocrinologists and American College of Endocrinology ; ADA = American Diabetes Association ; AGREE II = Appraisal of Guidelines for Research and Evaluation II ; GDG = guideline development group ; ICSI = Institute for Clinical Systems Improvement ; NICE = National Institute for Health and Care Excellence ; SIGN = Scottish Intercollegiate Guidelines Network ; VA/DoD = U.S. Department of Veterans Affairs and Department of Defense . Appendix Table 1 . Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment Peer Review The draft guidance statement was peer- review ed through Annals of Internal Medicine and was posted online for comments from ACP Regents and Governors , who represent ACP members at the regional level . The final guidance statement incorporated comments from peer review ers and ACP Regents and Governors . Public Panel Review The development of this guidance statement also included perspectives , values , and preferences of 2 CGC members who represent the public and a 7-member public panel . Summary of Evaluated Guidelines Using the AGREE II Instrument We review ed and rated 6 guidelines ( AACE/ACE [ 9 ] , ADA [ 10 ] , ICSI [ 8 ] , NICE [ 7 ] , SIGN [ 11 ] , and VA/DoD [ 12 ] ) , focusing solely on sections addressing HbA1c targets in patients with type 2 diabetes . Appendix Table 1 shows the detailed scaled domain scores and average quality ratings for each guideline , and the Appendix Figure shows average AGREE II scores for each item in each of the 6 domains . The fundamental difference between high- and low-scoring guidelines was methodology . The 2 lowest-scoring guidelines , AACE/ACE and ADA , scored lowest on stakeholder involvement , applicability , editorial independence , and scientific rigor . A systematic review is the backbone for any trustworthy guideline , but some guidelines might not be based on a systematic review or may not have made the review publicly available ( 14 , 15 ) . Several factors were important in considering guideline quality . For example , although many guidelines described benefits , adverse effects , and the strength and limitations of evidence or linked the evidence to the recommendation , they often inadequately described how they had considered or weighted these factors in developing the final recommendations . The guidelines frequently relied on selective reporting of studies or outcomes and focused on relative versus absolute effects and asymptomatic surrogate measures rather than patient-centered health outcomes . All of the review ed guidelines recommend individualizing HbA1c targets on the basis of patient characteristics , such as comorbid conditions and risk for hypoglycemia ( Appendix ) . The ADA and SIGN guidelines recommend a target of 7 % for the general population , whereas AACE/ACE recommends 6.5 % ( if it can be achieved safely ) . The NICE guideline specifies 6.5 % or 7 % , depending on the patient 's treatment regimen . Both ICSI and VA/DoD recommend target ranges . The ICSI guideline recommends less than 7 % to less than 8 % based on patient factors , whereas the VA/DoD recommends the following target ranges based on life expectancy and comorbid conditions : 6 % to 7 % for patients with a life expectancy greater than 10 to 15 years and no or mild microvascular complications ; 7 % to 8.5 % for those with established microvascular or macrovascular disease , comorbid conditions , or a life expectancy of 5 to 10 years ; and 8 % to 9 % for those with a life expectancy less than 5 years , significant comorbid conditions , advanced complications of diabetes , or difficulties in self-management attributable to mental status , disability , or other factors ( 12 ) . All guidelines recognize that HbA1c targets can be higher in patients with comorbid conditions and limited life expectancy . We looked into the evidence presented in these guidelines , specifically 5 large , long-term r and omized trials with a treat-to-target strategy and corresponding reports on extended follow-up ( 1623 ) . We summarize below the individual studies and result ing benefits and harms . Note that recent studies evaluating the effectiveness and safety of several newer diabetes drugs ( for example , recently approved sodiumglucose cotransporter-2 inhibitors , dipeptidyl peptidase-4 inhibitors , and glucagon-like peptide-1 receptor agonists ) were not considered in guideline sections pertaining to HbA1c targets because these studies were not design ed to evaluate treat-to-target strategies . Therefore , their findings are not described here . Benefits and Harms of Lower HbA1c Targets : Evidence From Clinical Trials Five large , long-term r and omized controlled trials investigated intensive ( achieved HbA1c levels , 6.3 % to 7.4 % ) versus less intensive ( achieved HbA1c levels , 7.3 % to 8.4 % ) IMPORTANCE Hypoglycemia commonly occurs in patients with diabetes mellitus ( DM ) and may negatively influence cognitive performance . Cognitive impairment in turn can compromise DM management and lead to hypoglycemia . OBJECTIVE To prospect ively evaluate the association between hypoglycemia and dementia in a biracial cohort of older adults with DM . DESIGN AND SETTING Prospect i ve population -based study . PARTICIPANTS We studied 783 older adults with DM ( mean age , 74.0 years ; 47.0 % of black race/ethnicity ; and 47.6 % female ) who were participating in the prospect i ve population -based Health , Aging , and Body Composition Study beginning in 1997 and who had baseline Modified Mini-Mental State Examination scores of 80 or higher . MAIN OUTCOME MEASURES Dementia diagnosis was determined during the follow-up period from hospital records indicating an admission associated with dementia or the use of prescribed dementia medications . Hypoglycemic events were determined during the follow-up period by hospital records . RESULTS During the 12-year follow-up period , 61 participants ( 7.8 % ) had a reported hypoglycemic event , and 148 ( 18.9 % ) developed dementia . Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event ( 34.4 % vs 17.6 % , P < .001 ; multivariate-adjusted hazard ratio , 2.1 ; 95 % CI , 1.0 - 4.4 ) . Similarly , older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with participants who did not develop dementia ( 14.2 % vs 6.3 % , P < .001 ; multivariate-adjusted hazard ratio , 3.1 ; 95 % CI , 1.5 - 6.6 ) . Further adjustment for stroke , hypertension , myocardial infa rct ion , and cognitive change scores produced similar results . CONCLUSION AND RELEVANCE Among older adults with DM , there seems to be a bidirectional association between hypoglycemia and dementia Epidemiological evidence reveals that patients with type 2 diabetes mellitus ( T2DM ) have an increased risk of neurodegenerative diseases ( NDs ) , including dementia and Parkinson 's disease ( PD ) . The effects of metformin exposure on dementia and PD risk in patients with T2DM are unknown . We evaluated the effects of metformin exposure on the risk of dementia and PD in patients with T2DM . We performed a cohort study by using Taiwan 's National Health Insurance Research Data base . We recruited 4651 patients in the metformin cohort and a comparable number of nonmetformin controls by using propensity score matching . Multivariate Cox proportional hazards regression was used to estimate the effects of metformin on the risk of dementia and PD after adjustment for several confounding factors . During the 12-year follow-up , the metformin cohort exhibited a higher risk of PD than the nonmetformin cohort ( hazard ratio [ HR ] : 2.27 , 95 % confidence interval [CI]=1.68 - 3.07 ) . The metformin cohort had an increased risk of all-cause dementia ( HR : 1.66 , 95 % CI=1.35 - 2.04 ) . Moreover , metformin exposure increased the risk of Alzheimer 's disease ( HR : 2.13 , 95 % CI=1.20 - 3.79 ) and vascular dementia ( HR : 2.30 , 95 % CI=1.25 - 4.22 ) . The effects of exposure duration and dosage on dementia and PD occurrence were also observed . Long-term metformin exposure in patients with T2DM may lead to the development of NDs , including dementia and PD . Additional large-scale , prospect i ve controlled trials are required to confirm the observed association in patients with T2DM BACKGROUND Type-2 Diabetes Mellitus ( DM-2 ) is an important risk factor for Alzheimer disease ( AD ) and vascular dementia ( VD ) . The role of insulinic therapy on cognitive decline is controversial . OBJECTIVE To evaluate cognitive impairment in patients with AD and DM-2 treated with either oral antidiabetic drugs or combination of insulin with other diabetes medications . METHODS 104 patients with mild-to-moderate AD and DM-2 were divided into two groups , according to antidiabetic pharmacotherapy : group A , patients treated with oral antidiabetic drugs and group B , patients treated with insulin combined with other oral antidiabetic medications . Cognitive functions were assessed by the Mini Mental State Examination ( MMSE ) and the Clinician 's Global Impression ( CGI ) , with a follow-up of 12 months . RESULTS At the end of the study , the MMSE scores showed a significant worsening in 56.5 % patients of group A and in 23.2 % patients of group B , compared to baseline MMSE scores ( P=.001 ) . Also CGI-C scores showed a significant worsening for all domains after 12 months in group A vs group B ( P=.001 ) . The two groups were matched for body mass index , serum lipids , triglycerides , Apo epsilon4 allele and smoke habit . Conversely , ischemic heart disease and hypertension were significantly higher in group B ( P=.002 ) . After adjustment for this risk variables , our results remained significant ( P=.001 ) . CONCLUSIONS Our study suggests that insulinic therapy could be effective in slowing cognitive decline in patients with AD 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 Diabetes and hyperinsulinemia may be risk factors for Alzheimer 's disease ( AD ) . We conducted a pilot study of metformin , a medication efficacious in treating and preventing diabetes while reducing hyperinsulinemia , among persons with amnestic mild cognitive impairment ( aMCI ) with the goal of collecting preliminary data on feasibility , safety , and efficacy . Participants were 80 men and women aged 55 to 90 years with aMCI , overweight or obese , without treated diabetes . We r and omized participants to metformin 1000 mg twice a day or matching placebo for 12 months . The co- primary clinical outcomes were changes from baseline to 12 months in total recall of the Selective Reminding Test ( SRT ) and the score of the Alzheimer 's Disease Assessment Scale-cognitive subscale ( ADAS-cog ) . The secondary outcome was change in relative glucose uptake in the posterior cingulate-precuneus in brain fluorodeoxyglucose positron emission tomography . Change in plasma Aβ42 was an exploratory outcome . The mean age of participants was 65 years . Fifty percent of participants were women . The only baseline variable that was different between the arms was the ADAS-Cog . Metformin could not be tolerated by 7.5 % of participants ; 15 % tolerated 500 mg/day , 35 % tolerated 1000 mg/day , 32.5 % tolerated 1500 mg/day , and only 10 % tolerated the maximum dose . There were no serious adverse events related to metformin . The 7.5 % of persons who did not tolerate metformin reported gastrointestinal symptoms . After adjusting for baseline ADAS-cog , changes in total recall of the SRT favored the metformin group ( 9.7±8.5 versus 5.3±8.5 ; p = 0.02 ) . Differences for other outcomes were not significant . A larger trial seems warranted to evaluate the efficacy and cognitive safety of metformin in prodromal AD OBJECTIVE Self-management of type 2 diabetes including avoidance of hypoglycemia is complex , but the impact of cognition on safe self-management is not well understood . This study aim ed to assess the effect of baseline cognitive function and cognitive decline on subsequent risk of severe hypoglycemia and to assess the effect of different glycemic strategies on these relationships . RESEARCH DESIGN AND METHODS Prospect i ve cohort analysis of data from the ACCORD trial included 2,956 adults aged ≥55 years with type 2 diabetes and additional cardiovascular risk factors . Cognitive tests ( Digit Symbol Substitution Test [ DSST ] , Rey Auditory Verbal Learning Test , Stroop Test , and Mini Mental Status Examination ) were conducted at baseline and 20 months . Study outcomes were incident confirmed severe hypoglycemia requiring medical assistance ( HMA ) and hypoglycemia requiring any assistance ( HAA ) . RESULTS After a median 3.25-year follow-up , a 5-point-poorer baseline score on the DSST was predictive of a first episode of HMA ( hazard ratio 1.13 [ 95 % CI 1.08–1.18 ] ) . Analyses of the other cognitive tests and of HAA were consistent with the DSST results . Cognitive decline over 20 months increased the risk of subsequent hypoglycemia to a greater extent in those with lower baseline cognitive function ( Pinteraction = 0.037 ) . R and omization to an intensive versus st and ard glycemic strategy had no impact on the relationship between cognitive function and the risk of severe hypoglycemia . CONCLUSIONS Poor cognitive function increases the risk of severe hypoglycemia in patients with type 2 diabetes . Clinicians should consider cognitive function in assessing and guiding their patients regarding safe diabetes self-management regardless of their glycemic targets Summary Dementia and non-insulin-dependent diabetes mellitus ( NIDDM ) are highly prevalent disorders in the elderly . Diabetes has repeatedly been reported to affect cognition , but its relation with dementia is uncertain . We therefore studied the association between diabetes and dementia in the Rotterdam Study , a large population -based study in the elderly . Of 6330 participants , aged 55 to 99 years old , complete information on diabetes and presence of dementia was available . Diabetes was diagnosed as use of anti-diabetes medication or r and om or post-load serum glucose over 11 mmol/l . Dementia was diagnosed through a stepped approach , including a sensitive screening of all participants and a comprehensive diagnostic work-up . Diabetes was present in 724 ( 11.4 % ) subjects . Of the 265 dementia patients 59 ( 22.3 % ) had diabetes . Multiple logistic regression analyses , adjusting for age and sex differences , revealed a positive association between diabetes and dementia ( odds ratio : 1.3 , 95 % confidence interval : 1.0–1.9 ) . In particular , strong associations were found between dementia and diabetes treated with insulin ( odds ratio : 3.2 , 95 % confidence interval : 1.4–7.5 ) . The relation was strongest with vascular dementia , but was also observed with Alzheimer 's disease . These associations were independent of educational attainment , smoking , body mass index , atherosclerosis , blood pressure and antihypertensive drug treatment , and could not be explained by clinical cerebral infa rct ions . The results suggest that NIDDM is associated with dementia . Alzheimer 's disease may be more frequent in elderly diabetic patients treated with insulin . [ Diabetologia ( 1996 ) 39 : 1392–1397 AIM Although hypoglycemia is associated with cognitive dysfunction , including dementia , in patients with type 2 diabetes mellitus ( DM ) , the data are equivocal . The purpose of this study was to investigate the association between hypoglycemia , dementia , and other cognitive dysfunctions . METHODS This was a prospect i ve observational study based upon the Korea National Diabetes Program ( KNDP ) . Among the 4540 participants in the KNDP cohort , individuals aged ⩾60years without any history of hypoglycemia or cognitive dysfunction ( n=1957 ) were included . Nationally representative data from the Health Insurance Review and Assessment Service of Korea cl aim data base were used to obtain a more precise determination of patient outcome . RESULTS During a mean follow-up period of 3.4±0.9years , 118 subjects experienced hypoglycemia-related events . The incidence of dementia and cognitive dysfunction was 7.5 cases per 1000 person-years ( PY ) and 0.61 cases per 1000 PY , respectively . In the subjects who experienced hypoglycemic events ( relative to those who did not ) , the incidence of dementia was significantly higher ( P=0.0139 ) , but the incidence of cognitive dysfunction was not ( P=0.1106 ) . Hypoglycemic events were associated with dementia ( HR , 2.689 ; 95 % CI , 1.080 - 6.694 , P=0.0335 ) following multiple adjustments . There was also a significant linear trend toward an increased dementia risk commensurate with an increasing number of hypoglycemic events ( P=0.0286 ) . CONCLUSIONS Hypoglycemia is significantly associated with the risk of dementia in Korean type 2 DM patients aged ⩾60years Objective : To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD . Background : Both dementia and diabetes are frequent disorders in elderly people . Methods : Prospect i ve population -based cohort study among 6,370 elderly subjects . At baseline study participants were examined for presence of diabetes mellitus . Nondemented participants were followed up , on average , for 2.1 years . Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup . To complete the follow-up , medical files were studied of persons who could not be reexamined . We estimated relative risks with proportional hazard regression , adjusting for age , sex , and possible confounders . Results : During the follow-up , 126 patients became demented , of whom 89 had AD . Diabetes mellitus almost doubled the risk of dementia ( relative risk [ RR ] 1.9 [ 1.3 to 2.8 ] ) and AD ( RR 1.9 [ 1.2 to 3.1 ] ) . Patients treated with insulin were at highest risk of dementia ( RR 4.3 [ 1.7 to 10.5 ] ) . Conclusion : The diabetes attributable risk for dementia of 8.8 % suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients Aims /hypothesisThe aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes . Methods A sample of 302 diabetic patients aged ≥70 years was assessed for dementia or cognitive impairment without dementia in 2001–2002 and a sub sample of non-demented patients ( n = 205 ) was followed to assess cognitive decline . A history of severe hypoglycaemia was determined from self-reports , physician assessment s and records of health service use for hypoglycaemia ( HSH ) . Prospect i ve HSH was determined up to 2006 . Data analysis , including multiple logistic and Cox regression models , was used to determine whether : ( 1 ) there were cross-sectional associations between hypoglycaemia and cognitive status , ( 2 ) historical hypoglycaemia predicted cognitive decline , and ( 3 ) baseline cognitive status predicted subsequent HSH . Results There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia . Independent risk factors for future HSH included dementia ( hazard ratio 3.00 , 95 % CI 1.06–8.48 ) and inability to self-manage medications ( hazard ratio 4.17 , 95 % CI 1.43–12.13 ) . However , there were no significant associations between historical hypoglycaemia , incident HSH and cognitive decline . Conclusions /interpretationDementia is an important risk factor for hypoglycaemia requiring health service utilisation . We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes Type 2 diabetes mellitus ( T2DM ) is associated with dementia . Mild cognitive impairment ( MCI ) is a key determinant in this association . It is not clear whether T2DM increases the risk of conversion from MCI to dementia . We plan to explore the relationship between T2DM-MCI and dementia and identify its potential risk factors . A prospect i ve community-based cohort study was conducted from March 2010 to March 2014 , including 634 participants with T2DM-MCI , 261 T2DM participants who were cognitively intact , and 585 MCI participants without diabetes . All cohort members received detailed annual evaluations to detect dementia onset during the 5 years of follow-up . The three cohorts were compared to assess differences in dementia onset . Furthermore , Cox proportional hazards regression was used to identify risk factors for dementia onset in the T2DM-MCI cohort . During follow-up , 152 and 49 subjects developed dementia in the MCI and cognitively-intact cohorts , amounting to an adjusted hazard ratio ( HR ) of 1.66 ( 95 % CI 1.07 - 2.26 ) . In a survival analysis of the cohorts , MCI accelerated the median progression to dementia by 2.74 years . In a multivariable analysis of the T2DM-MCI cohort , major risk factors for dementia were age > 75 years and longer duration s of diabetes , while significantly reduced risks of dementia were associated with oral hypoglycemic agents and HMG-CoA reductase inhibitors . Insulin was not associated with significantly changed risk . T2DM-MCI may aggravate the clinical picture as a concomitant factor . To minimize progression to dementia , it may be worthwhile to target several modifiable diabetes-specific features , such as the duration of disease , glycemic control , and antidiabetic agents AIMS Most diabetes mellitus ( DM ) patients have several comorbidities ; the correlation of these comorbidities with dementia in DM requires clarification . METHODS Using cl aims data from Taiwan National Health Insurance , we identified 33,709 DM adults before the year 2000 and r and omly selected 67,066 non-DM patients matched by sex and age . Subjects were followed until diagnosis with dementia , excluded due to death/withdrawal from the insurance program , or followed until 2011 . We compared the incidence and hazard ratio ( HR ) for dementia in both cohorts . RESULTS Comorbidities were more prevalent in DM patients , including hypertension , hyperlipidemia , stroke , coronary artery and /or kidney disease . The HR was higher for the DM cohort with comorbidities than those without : 1.88 vs. 1.46 with hypertension ; 1.56 vs. 1.39 with hyperlipidemia ; 1.73 vs. 1.37 with coronary artery disease ; 2.36 vs. 2.29 with stroke and 1.88 vs. 1.50 with kidney disease . The HR for dementia in diabetics rose from 1.41 in those without comorbidities to 2.49 in those with ≥4 comorbidities . In the DM cohort , HR was 1.22 for non-insulin-users and 1.41 for insulin-users , and 1.49 for type 1 DM and 1.23 for type 2 DM . CONCLUSION Diabetic patients have an elevated risk of dementia , and comorbidity increases this risk |
2,322 | 30,889,891 | There is a high level of evidence showing that MedDiet adherence plays a role in the primary and secondary prevention of cardiovascular disease ( CVD ) and improves health in overweight and obese patients .
There is moderate-to-high evidence that the MedDiet prevents increases in weight and waist circumference in non-obese individuals , and improves metabolic syndrome ( MetS ) and reduces its incidence .
Finally , there is moderate evidence that the MedDiet plays primary and secondary roles in the prevention of type 2 diabetes mellitus ( T2DM ) .
The MedDiet is effective in preventing obesity and MetS in healthy and at-risk individuals , in reducing mortality risk in overweight or obese individuals , in decreasing the incidence of T2DM and CVD in healthy individuals , and in reducing symptom severity in individuals with T2DM or CVD | The Mediterranean Diet ( MedDiet ) has been promoted as a means of preventing and treating cardiodiabesity .
The aim of this study was to answer a number of key clinical questions ( CQs ) about the role of the MedDiet in cardiodiabesity in order to provide a framework for the development of clinical practice guidelines . | BACKGROUND AND AIM We tested the hypothesis that an intervention with a Mediterranean diet ( MeDiet ) could mitigate the well-known harmful effects of abdominal obesity on cardiovascular health . METHODS AND RESULTS We assessed the relationship between baseline waist-to-height ratio ( WHtR ) and major cardiovascular events during a median follow-up of 4.8 years in the Prevention with Mediterranean Diet ( PREDIMED ) r and omized primary prevention trial , which tested a MeDiet against a control diet ( advice on a low-fat diet ) . We also examined whether the MeDiet intervention was able to counteract the detrimental cardiovascular effects of an increased WHtR. The trial included 7447 participants ( 55 - 80 years old , 57 % women ) at high cardiovascular risk but free of cardiovascular disease ( CVD ) at enrollment . An increased risk of CVD events ( myocardial infa rct ion , stroke , or cardiovascular death ) was apparent for the highest versus the lowest quartile of WHtR ( multivariable-adjusted hazard ratio : 1.98 ) ( 95 % confidence interval : 1.10 - 3.57 ; linear trend : p = 0.019 ) only in the control-diet group , but not in the two groups allocated to intervention with MeDiet ( p for interaction = 0.034 ) . This apparent interaction suggesting that the intervention counterbalanced the detrimental cardiovascular effects of adiposity was also significant for body mass index ( BMI ) ( p = 0.01 ) and waist circumference ( p = 0.043 ) . CONCLUSIONS The MeDiet may counteract the harmful effects of increased adiposity on the risk of CVD OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants . Design Prospect i ve cohort study with estimates of relative risk adjusted for sex , age , years of university education , total energy intake , body mass index , physical activity , sedentary habits , smoking , family history of diabetes , and personal history of hypertension . Setting Spanish university department . Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years . Main outcome measures Dietary habits assessed at baseline with a vali date d 136 item food frequency question naire and scored on a nine point index . New cases of diabetes confirmed through medical reports and an additional detailed question naire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up . Confirmed cases of type 2 diabetes . Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes . The incidence rate ratios adjusted for sex and age were 0.41 ( 95 % confidence interval 0.19 to 0.87 ) for those with moderate adherence ( score 3 - 6 ) and 0.17 ( 0.04 to 0.75 ) for those with the highest adherence ( score 7 - 9 ) compared with those with low adherence ( score < 3 ) . In the fully adjusted analyses the results were similar . A two point increase in the score was associated with a 35 % relative reduction in the risk of diabetes ( incidence rate ratio 0.65 , 0.44 to 0.95 ) , with a significant inverse linear trend ( P=0.04 ) in the multivariate analysis . Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes BACKGROUND The accumulation of abdominal fat increases risk of metabolic disorders and premature death . There is a dearth of prospect i ve data on the association between caloric beverage consumption and surrogate markers of abdominal adiposity . OBJECTIVE The aim of this study was to assess the relation between consumption of nonalcoholic caloric beverages , including soft drinks , fruit juice , whole milk , and skim and low-fat milk , and changes in waist circumference ( WC ) and odds of 10-y incidence of abdominal obesity . METHODS We conducted a prospect i ve , population -based study of 2181 Spanish men and women aged 25 - 74 y who were followed from 2000 to 2009 . We measured weight , height , and WC , and recorded data on diet and leisure-time physical activity ( LTPA ) with the use of vali date d question naires . We fit multivariable linear and logistic regression models . RESULTS A 100 kcal increase in soft drink consumption was associated with a 1.1 cm increase in WC ( P = 0.018 ) after 10 y of follow-up . Substitution of 100 kcal of soft drinks with 100 kcal of whole milk or 100 kcal of juice was associated with a 1.3 cm ( 95 % CI : 0.3 , 2.4 ) and 1.1 cm ( 95 % CI : 0.03 , 2.2 ) decrease in WC , respectively . Increasing consumption of soft drinks from baseline to follow-up led to WC gain compared with maintaining nonconsumption . Greater soft drink consumption was positively associated ( P = 0.029 ) with increased odds of 10-y incidence of abdominal obesity . CONCLUSION Adults ' consumption of soft drinks was associated with increased WC and odds of 10-y incidence of abdominal obesity . This association was moderate but consistent in all statistical models Objective : The aim of this work was to evaluate the combined effect of physical activity and 1 and 12 months ’ adherence to Mediterranean diet ( MD ) on serum total antioxidant capacity ( TAC ) in obese patients , as well as factors contributing to TAC . Methods : One hundred twenty-four patients were r and omly assigned to either MD combined with physical activity or st and ard hypolypemic diet ( SHD ) with physical activity . Both groups received counseling and education during the initial week and were invited for the follow-up visits , where data on body weight and blood sample s were collected . TAC was determined by Trolox equivalent antioxidant capacity and urate was determined using a uricase spectrophotometric method at the initial visit and after 1 and 12 months . Results : Eighty-four patients finished the 12-month program and were analyzed . The baseline and 1- and 12-month mean ( ±SD ) TAC values in the MD group ( n = 40 ) were 2.38 ± 0.48 , 2.51 ± 0.47 , and 2.47 ± 0.45 mmol Trolox equivalent (TE)/L , respectively . In the SHD group ( n = 44 ) , TAC values were 2.37 ± 0.49 , 2.48 ± 0.49 , and 2.31 ± 0.51 mmol TE/L , respectively . There was a statistically significant main effect for time ( p < 0.001 ) , as well as statistically significant time – diet interaction effect ( p = 0.009 ) . There was no statistically significant correlation between TAC and uric acid after 1 month ( p = 0.733 ) or 12 months ( p = 0.844 ) of the intervention . Based on the regression model , which included gender , diet , physical activity level , and percentage body weight change , the type of diet was the only significantly contributing factor to TAC change after the 12-month period , F = 3.867 , df = 3 , p = 0.012 , R = 0.358 , R2 = 0.128 . Conclusion : This r and omized controlled trial with diet and physical activity intervention and TAC as a primary outcome demonstrated initial antioxidant improvement in both MD and SHD groups and a long-term beneficial effect of MD . The results imply that diet composition — olive oil , nuts , and fish in particular — combined with physical activity modify antioxidant capacity BACKGROUND Adherence to a Mediterranean diet has been reported to increase longevity , but concerns have been expressed that such a diet may promote overweight and obesity . OBJECTIVE The objective was to investigate whether adherence to the traditional Mediterranean diet , as operationalized in a Mediterranean diet score , is associated with body mass index ( BMI ) and waist-to-hip ratio ( WHR ) . DESIGN In a general population sample of 23,597 adult men and women participating in the Greek European Prospect i ve Investigation into Cancer and Nutrition Study , a vali date d food-frequency question naire was interviewer-administered , and anthropometric , sociodemographic , physical activity , and other lifestyle characteristics were recorded . BMI and WHR were regressed on a score that reflects adherence to the traditional Mediterranean diet and potentially confounding variables . RESULTS In models in which total energy intake was included , adherence to the Mediterranean diet was unrelated to BMI in both sexes and was weakly related to WHR only in women . When energy intake was not controlled for , a 2-point increase in the score was found to correspond to increases of approximately 650 and 150 g in the weight of an average-height man and woman , respectively , whereas the WHR was found to increase by approximately 0.001 units in men and 0.004 units in women . CONCLUSIONS Adherence to a Mediterranean diet was essentially unrelated to BMI , with small differences depending on model choice and having no practical consequences . Overweight is a genuine problem in Greece and perhaps other Mediterranean countries , but it is likely to be related to limited physical activity in conjunction with excessive positive energy balance Purpose Mediterranean-type dietary pattern has been associated with lower risk of cardiovascular ( CVD ) and other chronic diseases , primarily in Southern European population s. We examined whether Mediterranean diet score ( MDS ) is associated with total , CVD , coronary heart disease ( CHD ) and stroke mortality in a prospect i ve cohort study in three Eastern European population s. Methods A total of 19,333 male and female participants of the Health Alcohol and Psychosocial factors in Eastern Europe ( HAPIEE ) study in the Czech Republic , Pol and and the Russian Federation were included in the analysis . Diet was assessed by food frequency question naire , and MDS was derived from consumption of nine groups of food using absolute cut-offs . Mortality was ascertained by linkage with death registers . Results Over the median follow-up time of 7 years , 1314 participants died . The proportion of participants with high adherence to Mediterranean diet was low ( 25 % ) . One st and ard deviation ( SD ) increase in the MDS ( equivalent to 2.2 point increase in the score ) was found to be inversely associated with death from all causes ( HR , 95 % CI 0.93 , 0.88–0.98 ) and CVD ( 0.90 , 0.81–0.99 ) even after multivariable adjustment . Inverse but statistically not significant link was found for CHD ( 0.90 , 0.78–1.03 ) and stroke ( 0.87 , 0.71–1.07 ) . The MDS effects were similar in each country cohort . Conclusion Higher adherence to the Mediterranean diet was associated with reduced risk of total and CVD deaths in these large Eastern European urban population s. The application of MDS with absolute cut-offs appears suitable for non-Mediterranean population BACKGROUND AND AIM No previous study has assessed the association between major dietary patterns and the risk of coronary heart disease ( CHD ) in a large cohort from a Mediterranean country . METHODS AND RESULTS We studied prospect ively 40,757 persons , aged 29 - 69 years , participating in the Spanish cohort of the EPIC study . Food consumption was collected between 1992 and 1996 with a vali date d history method . Individuals were followed-up until 2004 through record linkage with hospital discharge registers , population -based registers of myocardial infa rct ion , and mortality registers to ascertain CHD events ( fatal and non-fatal acute myocardial infa rct ion or angina requiring revascularization ) . Two major dietary patterns were identified from factor analysis . The first pattern was labeled as Westernized , because of the frequent consumption of refined cereals and red meat ; the second was called the evolved Mediterranean pattern , because of the frequent intake of plant-based foods and olive oil . During a median follow-up of 11 years , 606 CHD events were ascertained . No association was found between the Westernized pattern and CHD risk . In contrast , the score for the evolved Mediterranean pattern was inversely associated with CHD risk ( p for trend = 0.0013 ) ; when compared with the lowest quintile of the evolved Mediterranean pattern score , the multivariable hazard ratios for CHD were 0.77 ( 95 % confidence interval 0.61 - 0.98 ) for the second quintile , 0.64 ( 95 % CI 0.50 - 0.83 ) for the third quintile , 0.56 ( 95 % CI 0.43 - 0.73 ) for the fourth quintile , and 0.73 ( 95 % CI 0.57 - 0.94 ) for the fifth quintile . CONCLUSION A Mediterranean diet , as consumed in this study population , was associated with a lower risk of CHD Background Adherence to the Mediterranean diet ( MD ) is associated with reduced morbidity and mortality due to cardiovascular disease . However , how the MD exerts its effects is not fully known . Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED ( Prevención con Dieta Mediterránea ) study . Methods A total of 164 participants at high risk for cardiovascular disease were r and omized into three diet groups : MD supplemented with 50mL/d of extra virgin olive oil ( MD+EVOO ) or 30 g/d of nuts ( MD+Nuts ) and a low-fat diet . Changes in classical cardiovascular risk factors , inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention . Results Compared to participants in the low-fat diet group , those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic ( 6mmHg ) and diastolic ( 3mmHg ) blood pressure ( P = 0.02 ; both ) , as well as a reduction of 10 % and 8 % in LDL-cholesterol ( P = 0.04 ) , respectively . Patients in the MD+Nuts group showed a significant reduction of 34 % in CD40 expression on monocyte surface compared to low-fat diet patients ( P = 0.03 ) . In addition , inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45 % and 35 % and 95 % and 90 % in the MD+EVOO and MD+Nuts groups , respectively ( P<0.05 ; all ) compared to the low-fat diet group . Likewise , sICAM and P-selectin were also reduced by 50 % and 27 % , respectively in the MD+EVOO group ( P = 0.04 ) and P-selectin by 19 % in MD+Nuts group ( P = 0.04 ) compared to the low-fat diet group . Conclusions Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain , at least in part , the protective role of MD against ischemic heart disease . Trial Registration www.controlled-trials.com IS RCT Objective : To assess the influence of a Mediterranean dietary pattern ( MeDiet ) on anthropometric and body composition parameters in one of the centers of the PREDIMED r and omized dietary trial . Subjects/ Setting s : 351 Canarian free-living subjects aged 55 to 80 years , with type 2 diabetes or ≥3 cardiovascular risk factors . Intervention : Participants were r and omly assigned to one of 3 different dietary interventions : MeDiet + extra-virgin olive oil ( EVOO ) , MeDiet + nuts ( walnuts , almonds , and hazelnuts ) , or a control low-fat diet . Total energy intake was ad libitum . Outcome measures : Measures included changes in anthropometric measures ( weight , body mass index [ BMI ] and waist circumference [ WC ] ) , body fat distribution , energy , and nutrient intake after 1 year . Body composition ( percentage of total body fat [ % TBF ] , total fat mass [ TFM ] , free fat mass [ FFM ] , percentage of truncal fat [ % TrF ] , truncal fat mass [ TrFM ] ) and total body water ( TBW ) were estimated by octapolar electrical impedance analysis . Statistical analyses : Paired t tests were conducted to assess within-group changes . Analyses of variance ( ANOVAs ) were used to assess the effect of the dietary intervention on the percentage change in anthropometric variables , body composition , and dietary intake profile . All pairwise comparisons that were statistically significant in ANOVA were subsequently adjusted using the Benjamini-Hochberg test , which penalizes for multiple comparisons . Results : After 1 year of intervention , significant within-group reductions in all anthropometric variables were observed for the MeDiet + EVOO and the control group . The MeDiet + nuts group exhibited a significant reduction in WC and TBW . The control group showed a significant increase in % TBF and a reduction in TBW . The control group showed a significant increase in the percentage of total body fat and a reduction in TBW . However , we did not find any between-group significant difference in anthropometric or body composition changes . Conclusions : Mediterranean diets enriched with EVOO or specific mixed nuts ( walnuts , almonds , hazelnuts ) that contain approximately 40 % total fat can be alternative options to low-fat diets for weight maintenance regimes in older overweight or obese adults No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease ( CHD ) events in a Mediterranean population . This study examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospect i ve Investigation into Cancer and Nutrition . Analysis included 41,078 participants aged 29 - 69 years , recruited in 1992 - 1996 and followed up until December 2004 ( mean follow-up:10.4 years ) . Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence , measured by using an 18-unit relative Mediterranean diet score . A total of 609 participants ( 79 % male ) had a fatal or nonfatal confirmed acute myocardial infa rct ion ( n = 468 ) or unstable angina requiring revascularization ( n = 141 ) . After stratification by center and age and adjustment for recognized CHD risk factors , high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk ( hazard ratio = 0.60 , 95 % confidence interval : 0.47 , 0.77 ) . A 1-unit increase in relative Mediterranean diet score was associated with a 6 % reduced risk of CHD ( 95 % confidence interval : 0.91 , 0.97 ) , with similar risk reductions by sex . Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country , supporting its role in primary prevention of CHD in healthy population Background Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk . Methods In a multicenter trial in Spain , we assigned 7447 participants ( 55 to 80 years of age , 57 % women ) who were at high cardiovascular risk , but with no cardiovascular disease at enrollment , to one of three diets : a Mediterranean diet supplemented with extra‐virgin olive oil , a Mediterranean diet supplemented with mixed nuts , or a control diet ( advice to reduce dietary fat ) . Participants received quarterly educational sessions and , depending on group assignment , free provision of extra‐virgin olive oil , mixed nuts , or small nonfood gifts . The primary end point was a major cardiovascular event ( myocardial infa rct ion , stroke , or death from cardiovascular causes ) . After a median follow‐up of 4.8 years , the trial was stopped on the basis of a prespecified interim analysis . In 2013 , we reported the results for the primary end point in the Journal . We subsequently identified protocol deviations , including enrollment of household members without r and omization , assignment to a study group without r and omization of some participants at 1 of 11 study sites , and apparent inconsistent use of r and omization tables at another site . We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were r and omly assigned . Results A primary end‐point event occurred in 288 participants ; there were 96 events in the group assigned to a Mediterranean diet with extra‐virgin olive oil ( 3.8 % ) , 83 in the group assigned to a Mediterranean diet with nuts ( 3.4 % ) , and 109 in the control group ( 4.4 % ) . In the intention‐to‐treat analysis including all the participants and adjusting for baseline characteristics and propensity scores , the hazard ratio was 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ) for a Mediterranean diet with extra‐virgin olive oil and 0.72 ( 95 % CI , 0.54 to 0.95 ) for a Mediterranean diet with nuts , as compared with the control diet . Results were similar after the omission of 1588 participants whose study ‐group assignments were known or suspected to have departed from the protocol . Conclusions In this study involving persons at high cardiovascular risk , the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra‐virgin olive oil or nuts than among those assigned to a reduced‐fat diet . ( Funded by Instituto de Salud Carlos III , Spanish Ministry of Health , and others ; Current Controlled Trials number , IS RCT N35739639 . BACKGROUND AND AIM The Mediterranean diet is considered a model for healthy eating . However , prospect i ve evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce . The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area . METHODS AND RESULTS We followed-up 13,609 participants ( 60 percent women , mean age : 38 years ) initially free of cardiovascular disease ( CVD ) during 4.9 years . Participants were part of a prospect i ve cohort study of university graduates from all regions of Spain . Baseline diet was assessed using a vali date d 136-item food-frequency question naire . A 9-point score was used to appraise adherence to the Mediterranean diet . Incident clinical events were confirmed by a review of medical records . We observed 100 incident cases of CVD . In multivariate analyses , participants with the highest adherence to the Mediterranean diet ( score>6 ) exhibited a lower cardiovascular risk ( hazard ratio=0.41 , 95 % confidence interval [ CI ] : 0.18 - 0.95 ) compared to those with the lowest score ( <3 ) . For each 2-point increment in the score , the adjusted hazard ratios were 0.80 ( 95 % CI : 0.62 - 1.02 ) for total CVD and 0.74 ( 0.55 - 0.99 ) for coronary heart disease . CONCLUSIONS There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults BACKGROUND There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases . However , it is not clear whether this dietary pattern may be protective also against the development of obesity . OBJECTIVE We assessed the association between the adherence to the Mediterranean dietary pattern ( MDP ) , prospect i ve weight change , and the incidence of overweight or obesity . DESIGN We conducted a prospect i ve cohort study [ the European Prospect i ve Investigation into Cancer and Nutrition-Physical Activity , Nutrition , Alcohol Consumption , Cessation of Smoking , Eating Out of Home , and Obesity ( EPIC-PANACEA ) project ] in 373,803 individuals ( 103,455 men and 270,348 women ; age range : 25 - 70 y ) from 10 European countries . Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score ( rMED ; score range : 0 - 18 ) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet . The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression . RESULTS Individuals with a high adherence to the MDP according to the rMED ( 11 - 18 points ) showed a 5-y weight change of -0.16 kg ( 95 % CI : -0.24 , -0.07 kg ) and were 10 % ( 95 % CI : 4 % , 18 % ) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP ( 0 - 6 points ) . The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain . CONCLUSION This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity |
2,323 | 22,161,367 | Interventions did not appear to increase health inequalities although this was examined in fewer studies .
We found strong evidence to support beneficial effects of child obesity prevention programmes on BMI , particularly for programmes targeted to children aged six to 12 years . | BACKGROUND Prevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases , general health , development and well-being .
The international evidence base for strategies that governments , communities and families can implement to prevent obesity , and promote health , has been accumulating but remains unclear .
OBJECTIVES This review primarily aims to up date the previous Cochrane review of childhood obesity prevention research and determine the effectiveness of evaluated interventions intended to prevent obesity in children , assessed by change in Body Mass Index ( BMI ) .
Secondary aims were to examine the characteristics of the programs and strategies to answer the questions " What works for whom , why and for what cost ? " | OBJECTIVE : To vali date a range of dietary assessment instruments in general practice . METHODS : Using a r and omised block design , brief assessment instruments and more complex conventional dietary assessment tools were compared with an accepted " relative " st and ard -- a seven day weighed dietary record . The st and ard was checked using biomarkers , and by performing test-retest reliability in additional subjects ( n = 29 ) . OUTCOMES : Agreement with weighed record . Percentage agreement with weighed record , rank correlation from scatter plot , rank correlation from Bl and -Altman plot . Reliability of the weighed record . SETTING : Practice nurse treatment room in a single suburban general practice . SUBJECTS : Patients with risk factors for cardiovascular disease ( n = 61 ) or age/sex stratified general population group ( n = 50 ) . RESULTS : Brief self completion dietary assessment tools based on food groups caten during a week show reasonable agreement with the relative st and ard . For % energy from fat and saturated fat , non-starch polysaccharide , grams of fruit and vegetables and starchy foods consumed the range of agreement with the st and ard was : median % difference -6 % to 12 % , rank correlation 0.5 to 0.6 . This agreement is of a similar order to the reliability of the weighed record , as good as or better than test st and ard agreement for more time consuming instruments , and compares favourably with research instruments vali date d in other setting s. Under-reporting of energy intake was common ( 40 % ) and more likely if subjects were obese ( body mass idex ( BMI ) > or = 30 60 % under-reported ; BMI < 30 29 % , p < 0.001 ) . CONCLUSION : Under-reporting of absolute energy intake is common , particularly among obese patients . Simple self assessment tools based on food groups , design ed for practice nurse dietary assessment , show acceptable agreement with a st and ard , and suggest such tools are sufficiently accurate for clinical work , research , and possibly population dietary monitoring OBJECTIVE The validity of the 24-hour recall , 3-day food record , and 5-day food frequency was assessed to decide on a dietary assessment method for the National Heart , Lung , and Blood Institute ( NHLBI ) Growth and Health Study . DESIGN All subjects were assigned to one of three dietary assessment methods . Unobtrusive observers recorded types and amounts of foods eaten during lunch , and these were compared with the foods reported by the girls in the study . SETTING School lunchrooms in California and Ohio . SUBJECTS 58 girls , aged 9 and 10 years . MAIN OUTCOME MEASURES Reporting errors for dietary assessment methods . STATISTICAL ANALYSES PERFORMED Descriptive statistics , matched pair t tests , and Spearman correlation coefficients . RESULTS Comparison of the intakes of energy and selected macronutrients showed different ranges of , and median percentage absolute errors for , each dietary assessment method . Percentage absolute errors ranged between 20 and 33 for the 5-day food frequency method ; 19 and 39 for the 24-hour recall ; and 12 and 22 for the 3-day food record . The proportion of missing foods ( ie , observed food items not reported ) and phantom foods ( ie , reported food items not observed ) by each method were 46 % and 40 % , respectively , for the 5-day food frequency ; 30 % and 33 % , respectively , for the 24-hour recall ; and 25 % and 10 % , respectively , for the 3-day food record . APPLICATIONS/ CONCLUSIONS Errors in food reporting and quantification can vary with the type of dietary methodology . Agreement between observed and reported intakes from 3-day food records made it the best overall choice . On this basis , it was selected as the method of assessment for the NHLBI Growth and Health Study |
2,324 | 22,696,356 | There were no significant differences in adverse events , but these were poorly and inconsistently reported .
Overall , there was no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improved the clinical outcome .
These findings were limited to the routine use of glucocorticoids and can not be extrapolated to women with autoantibodies , unexplained infertility or recurrent implantation failure . | BACKGROUND In order to improve embryo implantation for in vitro fertilisation ( IVF ) or intracytoplasmic sperm injection ( ICSI ) cycles the use of glucocorticoids has been advocated .
It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer ( NK ) cell count and normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation .
OBJECTIVES To investigate whether the administration of glucocorticoids around the time of implantation improved clinical outcomes in subfertile women undergoing IVF or ICSI when compared to no glucocorticoid administration . | In a prospect i ve r and omized trial , 73 patients received prednisolone , 7.5 mg daily , for one cycle in addition to Clomid and /or gonadotrophins , while another 73 patients were not given the corticosteroid . In-vitro fertilization ( IVF ) result ed in 16 versus six clinical pregnancies in the prednisolone and the non-prednisolone group , respectively ( P less than 0.05 ) . Oestrogen was significantly higher under prednisolone during the ovulatory phase , while LH was significantly lower . The adrenal and rogen dehydroepi and rosterone sulphate was markedly depressed by prednisolone and testosterone was also markedly lower in the prednisolone group . A stress-related and rogen excess might occur in some patients undergoing IVF with consequent cystic degeneration of some follicles as in polycystic ovarian disease . Prednisolone might counteract this detrimental effect by depressing adrenal and ovarian and rogens OBJECTIVE To verify whether advantages can derive from the implementation of preimplantation genetic diagnosis for aneuploidy in patients with a poor prognosis of full-term pregnancy , compared with conventional treatment procedures . DESIGN A r and omized , controlled study . SETTING Reproductive Medicine Unit of the Società Italiana Studi Medicina della Riproduzione , Bologna , Italy . PATIENT(S ) In a total of 262 stimulated cycles , women presented with the following poor-prognosis indications : maternal age of > or = 36 years ( n = 157 ) , > or =3 previous IVF failures ( n = 54 ) , and an altered karyotype ( n = 51 ) . After giving consent , 127 patients underwent preimplantation genetic diagnosis for aneuploidy , whereas 135 controls underwent assisted zona hatching . INTERVENTION(S ) Analysis of chromosomes XY , 13 , 14 , 15 , 16 , 18 , 21 , and 22 was carried out with the fluorescence in situ hybridization technique in a blastomere biopsied from day 3 embryos . Assisted zona hatching was performed on day 3 embryos from the control group . MAIN OUTCOME MEASURE(S ) Embryo morphology and chromosomal status , number of transferred embryos , clinical pregnancies , implantation rates , and abortions . RESULT ( S ) In the study group , 717 embryos were analyzed by fluorescence in situ hybridization , and 60 % were chromosomally abnormal . A mean of 2.3+/-0.9 euploid embryos were transferred in 99 cycles , result ing in 37 clinical pregnancies ( 37 % ) and a 22.5 % ongoing implantation rate . In the control group , 126 cycles were performed with 3.2+/-1.3 embryos transferred , yielding 34 clinical pregnancies ( 27 % ) and a 10.2 % ongoing implantation rate . CONCLUSION ( S ) The advantage of selecting embryos with a normal chromosome complement has an immediate impact on the ongoing implantation rate , especially in patients aged > or = 38 years and carriers of an altered karyotype BACKGROUND Cancellation of assisted conception cycles because of poor ovarian response to gonadotrophins is a significant problem in assisted reproduction . Various adjuvant treatments have been suggested to improve responsiveness . This study reports on the potential benefits of low dose dexamethasone . METHODS Patients < 40 years of age were invited to participate in a twin centre prospect i ve double blind r and omized placebo controlled study . A total of 290 patients were recruited and computer r and omized using sealed envelopes to receive either 1 mg dexamethasone ( n = 145 ) or placebo tablets ( n = 145 ) in addition to a st and ard long protocol gonadotrophin-releasing hormone analogue with gonadotrophin stimulation regime . RESULTS A significantly lower cancellation rate for poor ovarian response was observed in the dexamethasone group compared with controls ( 2.8 versus 12.4 % respectively , P < 0.002 ) . Further comparisons between the dexamethasone group and controls were made of median fertilization rates ( 60 versus 61 % respectively , NS ) , implantation rates ( 16.3 versus 11.6 % respectively , NS ) and pregnancy rate per cycle started ( 26.9 versus 17.2 % , NS ) . The benefit was apparent in patients both with polycystic and normal ovaries . CONCLUSION Low dose dexamethasone co-treatment reduces the incidence of poor ovarian response . It may increase clinical pregnancy rates and should be considered for inclusion in stimulation regimes to optimize ovarian response Immunosuppression by exogenous corticosteroids has been used to improve the rates of embryo implantation and pregnancy in in-vitro fertilization ( IVF ) patients who have micromanipulated embryos replaced . The present study was conducted , in a prospect i ve design , to evaluate effects of corticosteroid on the pregnancy rate in IVF/embryo transfer patients who have non-micromanipulated embryos replaced . Infertile women < 40 years old with tubal factor were included in this study . Patients were grouped according to the different follicle stimulation protocol s , and received various doses of 16 beta-methylprednisolone ( 0 , 16 or 60 mg/day ) for 4 days from the day of oocyte retrieval . The mean age , duration of infertility , length of folliculogenesis and serum oestradiol concentrations at the time of human chorionic gonadotrophin ( HCG ) injection were not significantly different between control and corticosteroid-treated groups of patients . Short-term immunosuppression by 16 beta-methylprednisolone administration did not show any effects on the pregnancy and miscarriage rates in IVF/embryo transfer patients . Also , immunosuppression showed no dose effects in any groups . There was no relationship between the types of follicle stimulation protocol s and the effect of 16 beta-methylprednisolone . Therefore , we concluded that short-term immunosuppression by exogenous corticosteroids in IVF/embryo transfer patients who have embryos with intact zona pellucida replaced has neither positive nor negative effects on pregnancy rates OBJECTIVE To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome ( OHSS ) in high-risk patients after ovarian stimulation for in vitro fertilization ( IVF ) . DESIGN Prospect i ve r and omized study . PATIENTS Thirty-one patients who were stimulated with human menopausal gonadotropin ( hMG ) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and /or had a serum estradiol ( E2 ) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin ( hCG ) . INTERVENTIONS Patients were r and omly divided into two groups . Those who were r and omized to receive glucocorticoids ( group A ) ( n = 17 ) were administered intravenous hydrocortisone , 100 mg , immediately after ultrasound (US)-directed oocyte recovery . Prednisolone , 10 mg three times per day , was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days . Those in group B ( n = 14 ) did not receive any glucocorticoid treatment . In both groups , luteal support was provided by intramuscular injections of gestone 100 mg/d . RESULTS The two groups of patients were comparable in terms of age , duration of infertility , and total dose of hMG used . All had polycystic ovaries on US examination . On the day of hCG administration , the mean number of follicles in the two groups were 26.76 + /- 2.49 and 25.93 + /- 1.44 and the serum E2 concentration 13,404 + /- 710 and 13,915 + /- 901 pmol/L , respectively . There were no significant differences in the number of oocytes collected or in the fertilization , cleavage , and implantation rates in the two groups . The pregnancy rates per initiated cycle were 41.18 % and 35.71 % , respectively . Seven of the 17 patients ( 41.2 % ) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients ( 42.9 % ) who did not receive glucocorticoids . CONCLUSIONS Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF The effect of low dose immunosuppression with methylprednisolone during the first 4 days after oocyte retrieval on potential immune cell invasion of partially zona dissected embryos in utero was investigated in alternate in vitro fertilization patients ( n = 32 ) . The incidence of pregnancy was significantly higher in patients receiving methylprednisolone ( 7 of 18 , 39 % ) than in control patients ( 1 of 14 , 7 % ) . Twenty-eight percent ( 11 of 39 ) of the embryos replaced in the corticosteroid treated patients implanted , whereas only 7 % ( 2 of 31 ) of embryos in control patients had a fetal heart beat . There were no side effects reported in any of the patients receiving corticosteroids . It can be concluded that methylprednisolone supports implantation of embryos with small holes in their zonae . However , the actual mechanisms of corticosteroid support on the interaction between immune cells and micromanipulated embryos are not well understood Background Anti-thyroid antibodies ( ATA ) , even if not associated with thyroid dysfunction , are suspected to cause poorer outcome of in vitro fertilization ( IVF ) . Methods We retrospectively analyzed : ( a ) the prevalence of ATA in euthyroid infertile women , ( b ) IVF outcome in euthyroid , ATA+ patients , and ( c ) the effect of adjuvant treatments ( levothyroxine alone or associated with acetylsalicylic acid and prednisolone ) on IVF results in ATA+ patients . One hundred twenty-nine euthyroid , ATA+ women undergoing IVF were compared with 200 matched , ATA-controls . During IVF cycle , 38 ATA+ patients did not take any adjuvant treatment , 55 received levothyroxin ( LT ) , and 38 received LT + acetylsalicylic acid (ASA)+prednisolone ( P ) . Results The prevalence of ATA among euthyroid , infertile patients was 10.5 % , similar to the one reported in euthyroid women between 18 and 45 years . ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls . ATA+ patients receiving LT responded better to ovarian stimulation , but had IVF results as poor as untreated ATA+ women . Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients ( PR/ET 25.6 % and IR 17.7 % vs. PR/ET 7.5 % and IR 4.7 % , respectively ) , and overall IVF results comparable to patients without ATA ( PR/ET 32.8 % and IR 19 % ) . Conclusion These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment . This hypothesis must be verified in further r and omized , prospect i ve studies A group of 78 infertile women , diagnosed as having tubal factor infertility only , was enrolled in a prospect i ve , r and omized study conducted to determine whether the addition of different doses of glucocorticoids to the protocol of ovulation induction for in-vitro fertilization ( IVF ) would be beneficial . Oocyte numbers , percentage of fertilization , oestradiol , luteinizing hormone and follicle stimulating hormone serum concentrations , number of embryo transfers and pregnancy rate were evaluated . Compared to control cycles ( group A ; n = 24 ) , the addition of 0.5 mg ( group B ; n = 27 ) of 1 mg dexamethasone ( group C ; n = 27 ) , combined with the protocol of programmed oocyte retrieval for IVF patients in the study , demonstrated equivalent results . The mean numbers of oocytes retrieved were 10.8 + /- 3.9 in the control group , compared to 11.2 + /- 4.0 in group B and 10.5 + /- 3.6 in group C. The fertilization rates were 69 + /- 21 , 66 + /- 18 and 70 + /- 15 % respectively . The pregnancy rates were 20 , 16 and 20.8 % respectively . The addition of up to 1 mg dexamethasone daily to the protocol of ovulation induction for oocyte retrieval did not improve the overall IVF-embryo transfer outcome in patients with tubal factor infertility BACKGROUND Glucocorticoids have been used in conjunction with zona dissection to improve pregnancy and implantation rates in IVF patients . The aim of this prospect i ve r and omized study was to evaluate the effect of low-dose prednisolone in addition to the st and ard protocol , on pregnancy and implantation rates in routine ICSI patients before and after embryo replacement . METHODS A total of 313 patients in 360 consecutive cycles ( patients < 39 years old and with three or less than three ICSI attempts ) performed at our centre were r and omly assigned by computer-generated list to receive either prednisolone ( 10 mg/day in two divided doses ) , starting on the first day of ovarian stimulation and continuing for 4 weeks ( group A ) , or no treatment ( group B ) . RESULTS The mean age , number of previously failed IVF attempts , basal FSH levels and the mean rank of trials were comparable between groups A and B. The mean ( + /- SD ) number of metaphase II oocytes retrieved ( 11.9 + /- 5.5 versus 12.0 + /- 5.1 ) , 2-pronuclei fertilization rate ( 67.2 versus 65.8 % ) , the pregnancy and the implantation rates were not different between the study and control groups ( 49.0 and 23.6 % versus 50.0 and 23.3 % respectively ) . CONCLUSION Low-dose prednisolone treatment in addition to the st and ard protocol before and after embryo replacement does not appear to have a significant effect on pregnancy or implantation rates A prospect i ve non-r and omized study was undertaken to test whether immunosuppression improves implantation and pregnancy rates in an in-vitro fertilization-embryo transfer ( IVF-ET ) programme in patients with tubal factor infertility . Treatment involved ovarian stimulation , transvaginal oocyte retrieval , IVF-ET , and assessment of short-term administration of large doses of corticosteroids ( 60 mg of methyl-prednisone x 4 days ) . When compared to the group that did not receive immunosuppressive doses of methylprednisone ( group A ; mean age 31.85 + /- 4.09 years ) , those subjects who were treated ( group A2 ) showed a statistically significant increase in pregnancy ( P < 0.01 ) and take home baby rate ( P < 0.01 ) . Similar results were observed in subjects who received corticosteroids in their first IVF-ET attempt ( group B ; mean age 34.32 + /- 4.98 years ) . Our results suggest that immunosuppressive doses of corticosteroids administered for a short period of time to patients undergoing IVF-ET could significantly improve the implantation and pregnancy rates . Possible mechanisms of action of corticosteroids are proposed Abstract Purpose : To investigate the effects of short-term low-dose aspirin and /or steroid use on implantation and pregnancy rates in nonselected intracytoplasmic sperm injection ( ICSI ) cycles . Methods : Two-hundred patients undergoing ICSI for their first cycle were enrolled in this study . Participants were then r and omized into four groups on the embryo transfer day . Aspirin ( 100 mg/day ) in group A , prednisolone ( 10 mg/day ) in group B , aspirin along with prednisolone in group C were given while placebo was administrated to group D. Result : There were no statistically significant differences recorded in the demographic , ovulation induction cycle characteristics between groups . Mean transferred embryo number and mean top quality embryo number were similar among study groups . There were no statistical differences in implantation and pregnancy rates between study groups . Conclusion : Administration of low-dose aspirin and prednisolone alone or concomitant as a st and ard treatment have no positive effects on implantation and /or pregnancy rates OBJECTIVE To test whether adjuvant therapy with acetylsalicylic acid ( ASA ) and prednisolone ( ASA+Pred ) could improve the outcome of IVF in good-pregnancy prognosis patients . DESIGN Prospect i ve , r and omized study . SETTING University hospital . PATIENT(S ) Three hundred ninety-five infertile couples undergoing IVF . INTERVENTION(S ) Patients were r and omized to receive ASA+Pred ( n = 97 ) or nothing ( n = 298 ) , in addition to the routinely used IVF medications . MAIN OUTCOME MEASURE(S ) The primary endpoint was implantation rate ( IR ) . Secondary endpoints were number of retrieved oocytes and pregnancy rate ( PR ) . The blood flow in uterine arteries and subendometrial vessels also was measured . RESULT ( S ) Patients who received ASA+Pred had significantly more retrieved oocytes . The PR and IR in the study group and in controls were 50.5 % and 40.6 % and 25.1 % and 19.4 % , respectively , values that were not significantly different from one another . Uterine blood flows were not significantly different between treated and nontreated patients . A statistically significantly lower incidence of severe ovarian hyperstimulation syndrome was noted among treated patients who were at high risk of developing ovarian hyperstimulation syndrome ( 1.7 % vs. 6.5 % ) . CONCLUSION ( S ) Adjuvant treatment with ASA+Pred improves ovarian responsiveness but does not significantly improve uterine blood fluxes , PR , and IR . It may be effective in preventing the onset of severe ovarian hyperstimulation syndrome Abstract Purpose : A r and omized , nonplacebo controlled study was conducted to determine the effect of dexamethasone supplementation to a protocol of gonadotropin therapy in 42 “ low-responder patients ” aged 32 to 43 years . Methods : All underwent at least two previous cycles treated by gonadotropins for unexplained infertility , or anovulation . Human menopausal gonadotropin was started on day 4 of the menstrual cycle combined with dexamethasone 0.5 mg administered nightly , as an adjuvant . A group of “ low responders ” who did not receive dexamethasone served as the controls . The number of follicles , total amount of gonadotropins used , time required for stimulation , fertilization , peak estradiol levels and pregnancy rate were evaluated . Results : The number of developing follicles , estradiol levels , fertilization rate and pregnancy rate did not differ significantly . Conclusions : Although certain beneficial effects were observed in the literature in some of the infertile patients treated with corticosteroids , the overall results did not support daily , low-dose dexamethasone ( long-acting corticosteroid ) as a clinical ly useful adjuvant therapy for “ low responders ” during gonadotropin therapy OBJECTIVE To investigate the endometrial immunohistochemical staining of interleukin (IL)-12 and IL-18 and to quantify the CD56 bright natural killer ( NK ) cells in relation to Doppler vascular disorders . DESIGN Controlled clinical study . SETTING Research unit of a university hospital . PATIENT(S ) " : Thirty-five women with repeated implantation failure after ET in IVF and 12 fertile control patients .Ultrasound evaluation and endometrial biopsy on day 20 . MAIN OUTCOME MEASURE(S ) The balance between IL-12 and IL-18 , the number of NK cells , and the vascular status among fertile and implantation failure patients . RESULT ( S ) The control patients displayed normal vascular parameters , a weak anti-IL-12 staining , a consistent moderate stromal anti-IL-18 staining , and fewer than 15 NK cells/field . This pattern was observed among only 17 % ( 6/35 ) of the implantation failure group . The remaining patients fit into one of two patterns : [ 1 ] 37 % ( 13/35 ) had more than 40 NK cells/field with a strong anti-IL-12 and /or anti-IL-18 staining , and [ 2 ] the remaining 46 % ( 16/35 ) had a marked local depletion of IL-18 and IL-12 . Respectively , 85 % and 31 % of two groups displayed abnormal vascular parameters . CONCLUSION ( S ) Distinctions between the different local dysregulations of the cytokine network may provide clues for further exploration and treatment OBJECTIVE To establish whether there is any improvement in pregnancy and implantation rates after administration of " low-dose , " long-acting glucocorticoids during transfer of cryopreserved-thawed embryos . SETTING An IVF unit in a university hospital . DESIGN Prospect i ve , r and omized study . Ninety-nine consecutive transfer cycles of frozen-thawed embryos to the uterine cavity of r and omly chosen women diagnosed as having tubal factor infertility only . Fifty-two patients underwent transfer of frozen-thawed embryos and received 0.5 mg of dexamethasone ; 47 women ( control group ) did not receive the drug during transfer . PATIENTS Normal ovulatory patients with tubal factor infertility . INTERVENTIONS Oral dexamethasone administration before , during and after transfer of thawed embryos . MAIN OUTCOME MEASURES Pregnancy and implantation rates . RESULTS The pregnancy rate was 13.5 % ( 7/52 ) in patients treated with the " low-dose " regimen of dexamethasone compared with 12.8 % ( 6/47 ) in the control group . The implantation rate was similar . CONCLUSION Our results demonstrated that the use of 0.5 mg dexamethasone for an immuno-suppressive effect , administered for a short period to patients diagnosed as having " pure " tubal factor infertility , did not improve the implantation or pregnancy rates OBJECTIVE To evaluate the association of antinuclear antibodies ( ANA ) with outcome of in vitro fertilization-embryo transfer ( IVF-ET ) as well as the effect of short-term immunosuppression with prednisolone on implantation , clinical pregnancy and live birth rates following IVF-ET . STUDY DESIGN The study group consisted of 120 women , 22 - 42 years old , in whom IVF-ET was performed and whose ANA could be measured . Prednisolone ( 15 - 60 mg/d for 5 days ) was administered starting 1 day after oocyte retrieval to some women with or without ANA , without r and omization . The 223 IVF-ET cycles were divided into prednisolone-nontreated ANA-negative cycles , prednisolone-treated ANA-negative cycles , prednisolone-nontreated ANA-positive cycles and prednisolone-treated ANA-positive cycles . Retrospective analysis of rates of implantation , clinical pregnancy , and live birth were evaluated in the four groups . RESULTS Overall , ANA positivity was noted in 20.0 % of subjects ( 24/120 ) and 25.1 % of cycles ( 56/223 ) . Implantation and clinical pregnancy rates in the prednisolone-nontreated ANA-positive group were 0 % ( 0/41 transplanted embryos ) and 0 % ( 0/15 cycles ) , significantly lower than in the other groups . The live birth rate in this group was significantly lower than in the prednisolone-nontreated ANA-negative group and non-significantly tended to be lower than in the other 2 CONCLUSION Implantation , clinical pregnancy and live birth rates following IVF-ET were low when ANA was detected . Implantation and clinical pregnancy rates were improved significantly by prednisolone , but the live birth rate was not A total of 111 patients undergoing treatment for male factor infertility using SUZI participated in the trial for one treatment cycle only . They were allocated to have either corticosteroid treatment to induce immunosuppression or placebo . An elevated beta-hCG was found in 25 % ( 9 of 36 ) of patients having an ET and receiving treatment . The corresponding figure for the control group was 33 % ( 10 of 30 ) . On ultrasound examination , fetal hearts were found in 22 % ( 8 of 36 ) and 20 % ( 6 of 30 ) , respectively , of patients having an ET . chi 2 analysis showed no difference in the results . When the results were analyzed on a per oocyte basis there was no significant difference in the implantation rate OBJECTIVE To evaluate the safety and efficacy of immunosuppression as an adjunct to improving the success of in vitro fertilization/embryo transfer ( IVF-ET ) . STUDY DESIGN A r and omized , double-blind , placebo-controlled clinical trial . RESULTS Seventy-five patients were r and omized to receive either prednisone ( 39 patients , 51 % ) or placebo ( 36 patients , 49 % ) . Patients in both groups had similar ages and numbers of preembryos transferred . CONCLUSION Both the implantation and clinical pregnancy rates were higher in the prednisone group ( 16 % vs. 11 % and 43.5 % vs. 32.3 % , respectively ) . However , these differences did not achieve statistical significance . Evaluation of the ongoing pregnancy rate revealed little difference between the prednisone-treated patients ( 30.7 % ) and those receiving placebo ( 28.0 % ) . There were no side effects reported by patients in either group Many experimental and clinical findings indicate a disimmune pathogenesis of infertility associated with endometriosis . The most important modifications of cell-mediated immunity in endometriosis concern macrophage activity , increased both quantitatively and qualitatively . Peritoneal macrophages ( PM ) acquire the ability of producing lytic enzymes , that would be able to enhancing and stimulating implantation and proliferation of endometrial cells in peritoneal cavity . In these last years many experimental and clinical demonstrations have showed an immunosuppressive action of Danazol similar to corticosteroids . The Authors report their study on a comparison among Danazol 600 mg/daily for 3 months plus a local immunosuppressive treatment combined with superovulation and IPI , Danazol for 3 months plus superovulation and IPI and , as a control group , superovulation and IPI The purpose of the present study was to determine whether adrenal and rogen suppression with dexamethasone ( DEX ) during ovulation induction improves the outcome of in-vitro fertilization ( IVF ) cycles . A total of 25 patients with serum dehydroepi and rosterone sulphate ( DHEAS ) concentrations > 2.5 micrograms/ml were r and omized to receive either 0.5 mg DEX daily or placebo during ovulation induction with leuprolide acetate down-regulation plus human menopausal gonadotrophins ( HMG ) . Nine patients undergoing a subsequent IVF cycle were crossed over to the other treatment group . Ovarian responsiveness and IVF outcome variables analysed included number of follicles > 12 mm in diameter , serum oestradiol concentrations on the day of human chorionic gonadotrophin ( HCG ) administration , number of ampoules of HMG administered , number of oocytes retrieved , percentage of oocytes fertilized , number of embryos transferred , implantation rate and numbers of clinical pregnancies and live birth pregnancies . The 31 r and omized IVF cycles revealed a trend towards a higher implantation rate for the placebo-treated group compared to the DEX-treated group ( 24 versus 10 % ; P = 0.07 ) . The remainder of the IVF cycle variables revealed no statistically significant differences . In conclusion , the suppression of adrenal and rogens with DEX in women with DHEAS concentrations > 2.5 micrograms/ml appears to have no beneficial effects on ovarian responsiveness or clinical or live birth pregnancy rates BACKGROUND The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses OBJECTIVE To determine the role of estrogen in leukocyte recruitment to the human endometrium . DESIGN Prospect i ve , controlled in vivo study . SETTING Academic research laboratory . PATIENT(S ) Ten patients presenting for donor oocytes . INTERVENTION(S ) Endometrial biopsies for the evaluation of leukocyte population s were collected from perimenopausal women in two consecutive regulated cycles who were given two different regimens of estrogen with identical progesterone treatment . MAIN OUTCOME MEASURE(S ) Immunohistochemical identification of endometrial leukocyte population s and relative levels of expression of three chemokine genes . RESULT ( S ) The total uterine leukocyte population increased significantly when the women received oral estrogen , which result ed in higher serum estrogen levels . This rise in leukocytes was due to a significant increase in both the uterine natural killer cells and the macrophage population s. T-cell numbers did not change relative to circulating estrogen levels . The relative abundance of mRNA from three chemokines was also determined . No changes were found in the expression of M-CSF or MCP-1 . Interleukin 8 decreased in gl and s relative to estrogen levels . CONCLUSION ( S ) These data demonstrate that changes in circulating levels of estrogen can regulate the recruitment of bone marrow-derived cells to the uterine endometrium ; however , the mechanism whereby that occurs remains elusive The effect of the assisted zona hatching ( AZH ) procedure was investigated on 135 cycles with a poor prognosis of pregnancy due to : ( i ) maternal age > or = 38 years ( 45 cycles ) ; ( ii ) three or more failed in-vitro fertilization ( IVF ) attempts ( 70 cycles ) , and ( iii ) patients possessing both inclusion criteria ( 20 cycles ) . The control groups ( 113 cycles ) included patients possessing the same characteristics ( 42 , 53 and 18 cycles respectively ) and who did not undergo the AZH procedure . A total of 505 embryos was treated with AZH before transfer , result ing in : 14 , 25 and 6 clinical pregnancies . The percentage of clinical pregnancies per cycle was significantly higher than controls for the first ( 31 vs 10 % in control 1 , P < 0.05 ) and second groups ( 36 vs 17 % in control 2 , P < 0.05 ) . No significant difference in percentage of clinical pregnancies was found for the third group ( 30 vs 6 % ) . Similarly , higher rates of implantation were obtained ( 11.5 , 15 and 11 % ) compared to the respective controls ( 4 % , P < 0.02 ; 6.3 % , P < 0.01 ; and 1.5 % ) . The rate of miscarriage in the AZH groups was similar to that obtained in the controls ( 22 vs 21 % ) . Finally , the morphological analysis of the embryos transferred revealed that the poor prognosis condition is associated to a significantly slower rate of development and a higher rate of fragmentation . The present results indicate that AZH procedure improves pregnancy and implantation rates in patients with a poor prognosis of pregnancy by facilitating the hatching process in embryos which would otherwise be trapped inside the zona pellucida OBJECTIVE To determine if the immunotherapy with corticosteroids would improve pregnancy rate in infertile patients with ovulatory factor and patients with unexplained infertility who undergo superovulation with IUI . DESIGN Prospect i ve , controlled study . SETTING Division of Reproductive Endocrinology and Infertility , Department of Obstetrics and Gynecology , University of Ulsan , Seoul , Korea . PATIENTS Nine-one infertile patients with ovulatory factors and 78 patients with unexplained infertility who underwent superovulation with IUI . RESULTS The prevalence of autoantibodies ( antinuclear antibody , lupus anticoagulant , anticardiolipin antibody , antidouble-str and ed DNA antibody ) was elevated significantly in patients with unexplained infertility compared with patients with ovulatory infertility ( 20.5 % versus 3.3 % ) . Forty-five patients with ovulatory factor underwent 72 cycles of superovulation with IUI , receiving corticosteroids . Thirty-eight patients with unexplained infertility underwent 75 cycles of superovulation with IUI , receiving corticosteroids . Forty-six patients with ovulatory factor who underwent 66 cycles of superovulation with IUI and 40 patients with unexplained infertility who underwent 75 cycles of superovulation with IUI served as controls , not receiving corticosteroids . In patients with ovulatory factor , there were no significant differences between the corticosteroid treatment group and control group in clinical pregnancy rate ( 38.9 % versus 33.3 % ) or in spontaneous abortion rate ( 14.3 % versus 13.6 % ) . In patients with unexplained infertility , there was a significantly higher clinical pregnancy rate per cycle in the corticosteroid treatment group , with 45.3 % ( 34/75 ) compared with 29.3 % ( 22/75 ) in the control group but no difference between the corticosteroid treatment and control groups in spontaneous abortion rate ( 17.6 % versus 13.6 % ) . There were no side effects due to the use of corticosteroids Increased and rogen concentrations are thought to be detrimental to oocyte quality and reproductive potential . Adjuvant treatment with glucocorticoids has been tried to suppress and rogens in women undergoing infertility treatment . In the present study 20 infertile women with polycystic ovary syndrome were prospect ively r and omized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night , during st and ard in-vitro fertilization ( IVF ) treatment . Serum sample s for assays of gonadotrophins , steroids and sex hormone-binding globulin ( SHBG ) were collected before treatment , at down-regulation , and at oocyte retrieval . Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes , the rest according to the clinic 's routines . In the placebo group , serum dehydroepi and rosterone ( DHEA ) and dehydroepi and rosterone-sulphate ( DHEA-S ) did not change between down-regulation and oocyte retrieval , whereas adjuvant prednisolone result ed in a significant decrease . In follicular fluid , adjuvant prednisolone result ed in significantly lower concentrations of DHEA-S as compared to placebo , no other significant differences were found . No significant differences were found in embryo characteristics or pregnancy rates between the groups OBJECTIVE To determine the effect on pregnancy rate ( PR ) of low-dose glucocorticoid treatment in cycles without micromanipulation . DESIGN R and omized , prospect i ve , double-blinded , placebo-controlled trial . SETTING One university-based tertiary infertility center and two private infertility centers . PATIENTS All patients receiving st and ard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study . Patients having micromanipulation were excluded from this study . INTERVENTIONS Participating patients were r and omized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion . Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days . Cryopreservation and stimulation cycles were managed according to pre-established protocol s for all patients . A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound . RESULTS A total of 206 stimulation patients and 61 cryopreservation patients were r and omized and had an ET . Patient characteristics were similar between groups . The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9 % versus 40.8 % and 12.8 % versus 11.7 % for stimulation cycles and 30.3 % versus 25 % and 9.9 % versus 7.4 % for cryopreservation cycles , respectively . None of these differences were statistically significant . CONCLUSIONS Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates OBJECTIVE This study investigated the role of a steroid pretreatment on the pregnancy rate and pregnancy outcomes in patients positive for antithyroid antibodies who were undergoing induction of ovulation and intrauterine insemination ( IUI ) . METHODS A double-blind , r and omized , prospect i ve cohort study was conducted on infertile women who met the following criteria : infertility for ≥ 1 year , age 20 - 38 years , no more than 2 previous assisted reproduction treatment cycles , regular spontaneous menstrual cycles , no treatments 1 month before recruitment , normal uterine cavity , and bilateral tubal patency . The patients were divided into 2 groups : a study group of infertile women with antithyroid autoimmunity ( radioimmunoassay positive with titer > 100 U/mL ) and a control group of infertile women without antithyroid autoimmunity . The patients with antithyroid autoimmunity were r and omly assigned in a blinded manner to an intervention group treated with prednisone ( administered orally for 4 weeks before IUI ) or a group given matching placebo . The primary objective was to compare the pregnancy and miscarriage rates among all 3 the groups . RESULTS The study included 98 infertile women : 48 with antithyroid autoimmunity ( antibody positive ) and 50 without antithyroid autoimmunity ( antibody negative ) . The study groups were comparable for baseline characteristics ( age , race , body mass index , hormonal pattern , number of smokers , previous miscarriage ) . In the antithyroid antibody-positive group , the pregnancy rate was 33.3 % ( 8/24 ) among women treated with prednisone compared with 8.4 % ( 2/24 ) among women who received placebo ( odds ratio [ OR ] = 5.5 ; 95 % CI , 1.13 - 25.76 ; P = 0.03 ) . In the antibody-negative group , the pregnancy rate was 8.0 % ( 4/50 ) . Among the pregnancies , the miscarriage rate was 70 % ( 7/10 ) versus 75 % ( 3/4 ) for women with or without antithyroid antibodies , respectively ( P = NS ) ; the miscarriage rate was 75 % ( 6/8 ) for women treated with prednisone versus 50 % ( 1/2 ) for women taking placebo ( P = 0.49 ) . No adverse effects were reported . CONCLUSIONS In this small cohort study of infertile women with antithyroid antibodies undergoing induction of ovulation and IUI , prophylactic therapy with prednisone was associated with a significantly higher rate of pregnancy compared with placebo . The miscarriage rate was not significantly different among the 3 groups |
2,325 | 25,697,132 | Conclusions Exercise may be a useful treatment for anxiety , but lack of data from rigorous , method ologically sound RCTs precludes any definitive conclusions about its effectiveness | Background Exercise has been shown to reduce symptoms of anxiety , but few studies have studied exercise in individuals preselected because of their high anxiety .
Purpose The objective of this study is to review and critically evaluate studies of exercise training in adults with either high levels of anxiety or an anxiety disorder . | Study objective : To determine the association between a clinician assessment of temperament in early adulthood and cause specific mortality . Design : Prospect i ve observational study . Setting : Glasgow University . Participants : 9239 male former students aged 16–30 ( mean 20.5 ) years who participated in an ongoing health survey from 1948–68 . A physician recorded free text assessment of temperament , which seemed to capture aspects of personality ( trait ) and mental health ( state ) , was coded into : stable , anxious , schizoid , hypomanic , odd , depressed , immature , hypochondriacal , unstable , and obsessive . Associations between temperament and mortality were investigated using Cox proportional hazards models . Main results : There were 878 deaths . Most students—8342 (90.3%)—were assessed as stable , the remaining 897 ( 9.7 % ) having at least one , and 103 ( 1.1 % ) having more than one , temperament type . The second most common temperament was anxiety , recorded in 520 ( 5.6 % ) students . In multivariable analyses , having at least one temperament type was associated with increased all cause and stroke mortality , hazard ratios ( 95 % confidence intervals ) : 1.23 ( 1.01 to 1.50 ) and 1.95 ( 1.06 to 3.59 ) respectively , compared with stable students . Students with more than one temperament type had higher risk of death from : all causes , 2.05 ( 1.36 to 3.09 ) ; stroke , 3.26 ( 1.01 to 10.56 ) ; and cancer , 2.90 ( 1.62 to 5.20 ) . Anxiety was positively associated with all cause and cancer mortality , respective hazard ratios : 1.36 ( 1.07 to 1.72 ) and 1.51 ( 1.04 to 2.20 ) . Men labelled hypomanic had increased cardiovascular mortality risk , 1.90 ( 1.05 to 3.44 ) . Conclusions : Markers of early adult psychological distress are associated with increased mortality . Mechanisms underlying these associations require investigation Background : Social anxiety disorder ( SAD ) is characterized by distorted self-views . The goal of this study was to examine whether mindfulness-based stress reduction ( MBSR ) alters behavioral and brain measures of negative and positive self-views . Methods : Fifty-six adult patients with generalized SAD were r and omly assigned to MBSR or a comparison aerobic exercise ( AE ) program . A self-referential encoding task was administered at baseline and post-intervention to examine changes in behavioral and neural responses in the self-referential brain network during functional magnetic resonance imaging . Patients were cued to decide whether positive and negative social trait adjectives were self-descriptive or in upper case font . Results : Behaviorally , compared to AE , MBSR produced greater decreases in negative self-views , and equivalent increases in positive self-views . Neurally , during negative self versus case , compared to AE , MBSR led to increased brain responses in the posterior cingulate cortex ( PCC ) . There were no differential changes for positive self versus case . Secondary analyses showed that changes in endorsement of negative and positive self-views were associated with decreased social anxiety symptom severity for MBSR , but not AE . Additionally , MBSR-related increases in dorsomedial prefrontal cortex ( DMPFC ) activity during negative self-view versus case were associated with decreased social anxiety related disability and increased mindfulness . Analysis of neural temporal dynamics revealed MBSR-related changes in the timing of neural responses in the DMPFC and PCC for negative self-view versus case . Conclusion : These findings suggest that MBSR attenuates maladaptive habitual self-views by facilitating automatic ( i.e. , uninstructed ) recruitment of cognitive and attention regulation neural networks . This highlights potentially important links between self-referential and cognitive-attention regulation systems and suggests that MBSR may enhance more adaptive social self-referential processes in patients with SAD BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p < /=.05 ) , as measured by the Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder OBJECTIVES The aim of the study was to determine the status of the autonomic nervous system ( ANS ) in anxiety disorder patients and to evaluate possible exercise intervention in order to improve the ANS and overall psychiatric status of patients . PATIENTS AND METHODS The ANS function was monitored via means of heart rate variability ( HRV ) changes during a 6-week hospitalization at the Psychiatric Clinic of University Hospital in Olomouc . The status of ANS was monitored by the new evaluation method of spectral analysis ( SA ) of HRV . The research involved 43 anxiety patients ( 29 women and 14 men ) who underwent six weeks of intensive psychotherapy ; part of the test group also participated in regular aerobic exercise . RESULTS In the sense of autonomic dysfunction we can not give clear-cut answers to the question whether the autonomic dysfunction could be one of the predictors of anxiety disorder , although our results suggest lower vagal representation in the spectra . Unlike in the healthy population the exercise had a positive impact only on a limited number of patients . Regular endurance exercise on a stationary bicycle had a positive impact on the ANS efficiency only in patients with primary ANS activity reduction . In patients with normal ANS efficiency the exercise intervention had no effect ; in some cases we even found activity reduction during the hospitalization period . However , the exercise had a positive effect on the course and outcome of the applied therapy in all patients . CONCLUSIONS ANS disturbances have not been exhibited in some patients suffering from anxiety disorder . Due to the positive impact of regular physical activity on cardiovascular , metabolic , neural , and psychological changes in organism , monitored exercise should be implemented into therapeutic programs for patients with anxiety disorders Background : Interrelations of exercise , mood , and weight reduction are unclear in the behavioral treatment of obesity . Methods : Obese women volunteers with high tension ( anxiety ) ( T ) , depression ( D ) , or total mood disturbance ( TMD ) scores , who were previously r and omized into conditions of ( 1 ) exercise supported by The Coach Approach : a protocol based on social cognitive and self-efficacy theory ( CA ; n = 53 , 66 , and 60 , respectively ) , ( 2 ) personal demonstration and follow up of exercise methods ( EX ; n = 27 , 27 , and 21 , respectively ) , and ( 3 ) exercise suggested through written information only ( INFO ; n = 24 , 28 , and 20 , respectively ) , were subjects . Identical nutrition information was provided to all subjects in a small group format . Results : Minutes of exercise over the 6-month study were greatest in the CA condition , with minutes in the EX condition greater than the INFO condition . T , D , and TMD scores were reduced to normal levels mostly in the CA condition , with the EX condition having significantly more normalized D scores than the INFO . Across conditions , normalized mood scores generally predicted a greater reduction in waist circumference , with CA associated with additional benefits when D scores were considered . Conclusion : Properly accounting for exercise-induced mood change may be important in the behavioral treatment of obesity Background : Exercise training may be especially helpful for patients with generalized anxiety disorder ( GAD ) . We conducted a r and omized controlled trial to quantify the effects of 6 weeks of resistance ( RET ) or aerobic exercise training ( AET ) on remission and worry symptoms among sedentary patients with GAD . Methods : Thirty sedentary women aged 18–37 years , diagnosed by clinicians blinded to treatment allocation with a primary DSM-IV diagnosis of GAD and not engaged in any treatment other than pharmacotherapy , were r and omly allocated to RET , AET , or a wait list ( WL ) . RET involved 2 weekly sessions of lower-body weightlifting . AET involved 2 weekly sessions of leg cycling matched with RET for body region , positive work , time actively engaged in exercise , and load progression . Remission was measured by the number needed to treat ( NNT ) . Worry symptoms were measured by the Penn State Worry Question naire . Results : There were no adverse events . Remission rates were 60 % , 40 % , and 30 % for RET , AET , and WL , respectively . The NNT was 3 ( 95 % CI 2 to 56 ) for RET and 10 ( 95 % CI –7 to 3 ) for AET . A significant condition-by-time interaction was found for worry symptoms . A follow-up contrast showed significant reductions in worry symptoms for combined exercise conditions versus the WL . Conclusions : Exercise training , including RET , is a feasible , low-risk treatment that can potentially reduce worry symptoms among GAD patients and may be an effective adjuvant , short-term treatment or augmentation for GAD . Preliminary findings warrant further investigation BACKGROUND Several studies have suggested an increased risk of fatal coronary heart disease ( CHD ) among patients with panic disorder , phobic anxiety , and other anxiety disorders . We prospect ively examined this association in the Normative Aging Study . METHODS AND RESULTS An anxiety symptoms scale was constructed out of five items from the Cornell Medical Index , which was administered to the cohort at baseline . During 32 years of follow-up , we observed 402 cases of incident coronary heart disease ( 137 cases of nonfatal myocardial infa rct ion , 134 cases of angina pectoris , and 131 cases of fatal CHD : made up of 26 cases of sudden cardiac death and 105 cases of nonsudden death ) . A nested case-control design ( involving 1869 control subjects who remained free of diagnosed CHD ) was used to assess the association between anxiety and risk of CHD . Compared with men reporting no symptoms of anxiety , men reporting two or more anxiety symptoms had elevated risks of fatal CHD ( age-adjusted odds ratio [ OR ] = 3.20 , 95 % confidence interval [ CI ] : 1.27 to 8.09 ) , and sudden death ( age-adjusted OR = 5.73 , 95 % CI : 1.26 to 26.1 ) . The multivariate OR after adjusting for a range of potential confounding variables was 1.94 ( 95 % CI : 0.70 - 5.41 ) for fatal CHD and 4.46 ( 95 % CI : 0.92 - 21.6 ) for sudden death . No excess risks were found for nonfatal myocardial infa rct ion or angina . CONCLUSIONS These data suggest an association between anxiety and fatal coronary heart disease , in particular , sudden cardiac death Background : Previous studies have suggested that physical exercise can reduce symptoms for subjects suffering from panic disorder ( PD ) . The efficacy of this intervention has so far not been compared to an established psychotherapy , such as cognitive behaviour therapy ( CBT ) . Assessment of controlled long-term effects and the clinical significance of the treatment are also lacking . Aim : To compare physical exercise to CBT as treatment for PD , and assess controlled long-term and clinical ly significant effects . Method : PD- patients were r and omized to either three weekly sessions of physical exercise ( n = 17 ) , or one weekly session of CBT ( n = 19 ) . Both treatments ran for 12 weeks , were manualized and administered in groups . Patients were assessed twice before the start of treatment , at post-treatment and at 6 and 12 months thereafter . Primary outcome - measures consisted of the Mobility Inventory ( MI ) , the Agoraphobia Cognitions Question naire ( ACQ ) and the Body Sensations Question naire ( BSQ ) . Results : A two-way repeated measures MANOVA of these measures demonstrated a significant effect of time , F(16 , 544 ) = 7.28 , p < .01 , as well as a significant interaction effect , F(16 , 544 ) = 1.71 , p < .05 , in favour of CBT . This finding was supported by the assessment of clinical ly significant changes of avoidant behaviour and of treatment-seeking one year later . Conclusion : Group CBT is more effective than group physical exercise as treatment of panic disorder , both immediately following treatment and at follow-up assessment Background We evaluated the association of symptoms of anxiety and depression with fatal and non-fatal cardiovascular disease events among patients with coronary heart disease and considered several potential underlying pathogenetic links . Design This was a prospect i ve cohort study . Methods In this study , including coronary heart disease patients undergoing an in-patient rehabilitation program , symptoms of anxiety and depression were evaluated with the Hospital Anxiety and Depression Scale ( HADS ) . Fatal and non-fatal cardiovascular disease events were determined during a 3-year follow-up . Results Of the 1052 patients with CHD 16.1 % showed a borderline and 8.3 % a manifest anxiety symptoms score , whereas 11.8 and 5.9 % showed a borderline and manifest depressive symptoms score , respectively . During the 3-year follow-up fatal and non-fatal cardiovascular disease events were observed in 73 ( 6.9 % ) patients . After adjustment for covariates , patients having manifest anxiety symptoms had a statistically significant hazard ratio ( HR ) of 2.32 [ 95 % confidence interval ( CI ) 1.14 - 4.74 ] for a cardiovascular disease event , and patients with depressive symptoms had an HR of 1.47 ( 95 % CI 0.62 - 3.51 ) compared to other patients . In a model considering anxiety and depressive symptom scores simultaneously , the hazard ratio for a cardiovascular disease event associated with anxiety symptoms increased to 3.31 ( 95 % CI 1.32 - 8.27 ) , whereas the hazard ratio associated with depressive symptoms decreased ( HR 0.62 ; 95 % CI 0.20 - 1.87 ) . We found a positive association of increased anxiety scores with body mass index and systolic blood pressure . Conclusions The study suggests an important role especially for symptoms of anxiety for long-term prognosis of patients with known coronary heart disease . It furthermore suggests that several pathogenetic links may partly explain the increased risk Abstract Anxiety sensitivity , or the belief that anxiety-related sensations can have negative consequences , has been shown to play an important role in the etiology and maintenance of panic disorder and other anxiety-related pathology . Aerobic exercise involves exposure to physiological cues similar to those experienced during anxiety reactions . The present study sought to investigate the efficacy of a brief aerobic exercise intervention for high anxiety sensitivity . Accordingly , 24 participants with high anxiety sensitivity scores ( Anxiety Sensitivity Index-Revised scores > 28 ) were r and omly assigned to complete either six 20-minute sessions of aerobic exercise or a no-exercise control condition . The results indicated that individuals assigned to the aerobic exercise condition reported significantly less anxiety sensitivity subsequent to exercise , whereas anxiety sensitivity scores among non-exercisers did not significantly change . The clinical research and public health implication s of these findings are discussed , and several potential directions for additional research are recommended OBJECTIVE Effective treatments for social anxiety disorder ( SAD ) exist , but additional treatment options are needed for nonresponders as well as those who are either unable or unwilling to engage in traditional treatments . Mindfulness-based stress reduction ( MBSR ) is one nontraditional treatment that has demonstrated efficacy in treating other mood and anxiety disorders , and preliminary data suggest its efficacy in SAD as well . METHOD Fifty-six adults ( 52 % female ; 41 % Caucasian ; age mean [ M ] ± st and ard deviation [ SD ] : 32.8 ± 8.4 ) with SAD were r and omized to MBSR or an active comparison condition , aerobic exercise ( AE ) . At baseline and post-intervention , participants completed measures of clinical symptoms ( Liebowitz Social Anxiety Scale , Social Interaction Anxiety Scale , Beck Depression Inventory-II , and Perceived Stress Scale ) and subjective well-being ( Rosenberg Self-Esteem Scale , Satisfaction with Life Scale , Self-Compassion Scale , and UCLA-8 Loneliness Scale ) . At 3 months post-intervention , a subset of these measures was readministered . For clinical significance analyses , 48 healthy adults ( 52.1 % female ; 56.3 % Caucasian ; age [ M ± SD ] : 33.9 ± 9.8 ) were recruited . MBSR and AE participants were also compared with a separate untreated group of 29 adults ( 44.8 % female ; 48.3 % Caucasian ; age [ M ± SD ] : 32.3 ± 9.4 ) with generalized SAD who completed assessment s over a comparable time period with no intervening treatment . RESULTS A 2 ( Group ) x 2 ( Time ) repeated measures analyses of variance ( ANOVAs ) on measures of clinical symptoms and well-being were conducted to examine pre-intervention to post-intervention and pre-intervention to 3-month follow-up . Both MBSR and AE were associated with reductions in social anxiety and depression and increases in subjective well-being , both immediately post-intervention and at 3 months post-intervention . When participants in the r and omized controlled trial were compared with the untreated SAD group , participants in both interventions exhibited improvements on measures of clinical symptoms and well-being . CONCLUSION Nontraditional interventions such as MBSR and AE merit further exploration as alternative or complementary treatments for SAD The effects of Kouk Sun Do ( KSD ) , a mind-body exercise on mental health in university students , were investigated in this pilot study . University students ( N = 30 ) with self-reported anxiety symptoms were r and omly assigned to either the treatment group or the waiting list control group . Eighteen participants ( N = 18 ; seven in the treatment group and 11 in the waiting list control group ) completed a pre-test and a post-test , and 12 participants dropped out before or during the intervention . Ten 70-min KSD exercise sessions were conducted three times per week over a 4-week period . Trait anxiety , depressive symptoms and general self-efficacy in coping with stress were measured with the pre-test and the post-test . Qualitative data were collected using open-ended questions regarding benefits of KSD at the last session . A two ( group ) by two ( time ) repeated-measure analysis of variance was used to analyse the data . Trait anxiety and depressive symptoms decreased whereas general self-efficacy increased over a 4-week period . The treatment group had significantly reduced trait anxiety and depressive symptoms compared with the control group across time . Qualitative data provided support that the self-induced relaxation effects of KSD may lead to reduced anxiety A group r and omized trial of adding a home-based walking program to a st and ard group cognitive behavioral therapy ( GCBT+EX ) was compared with groups receiving GCBT and educational sessions ( GCBT+ED ) . The study was implemented in an outpatient clinic providing GCBT for clients diagnosed with panic disorder , generalized anxiety disorder or social phobia . Pre- and post-treatment measures included the self-report depression , anxiety , and stress scale ( DASS-21 ) and measures of physical activity . From January 2004 to May 2005 , six groups were allocated to GCBT+EX ( n=38 ) and five to GCBT+ED ( n=36 ) . Analysis of covariance for completed cases ( GCBT+EX , n=21 ; GCBT+ED , n=20 ) , adjusting for the group design , baseline DASS-21 scores , and anxiety diagnosis showed significant effect for GCBT+EX on depression , anxiety , and stress ( regression coefficients=-6.21 , -3.41 , and -5.14 , respectively , p<0.05 ) compared to the GCBT+ED . The potential of exercise interventions as adjunct to GCBT for anxiety disorder needs to be further explored Mindfulness-based stress reduction ( MBSR ) is thought to reduce emotional reactivity and enhance emotion regulation in patients with social anxiety disorder ( SAD ) . The goal of this study was to examine the neural correlates of deploying attention to regulate responses to negative self-beliefs using functional magnetic resonance imaging . Participants were 56 patients with generalized SAD in a r and omized controlled trial who were assigned to MBSR or a comparison aerobic exercise ( AE ) stress reduction program . Compared to AE , MBSR yielded greater ( i ) reductions in negative emotion when implementing regulation and ( ii ) increases in attention-related parietal cortical regions . Meditation practice was associated with decreases in negative emotion and social anxiety symptom severity , and increases in attention-related parietal cortex neural responses when implementing attention regulation of negative self-beliefs . Changes in attention regulation during MBSR may be an important psychological factor that helps to explain how mindfulness meditation training benefits patients with anxiety disorders Anxiety sensitivity is a known precursor to panic attacks and panic disorder , and involves the misinterpretation of anxiety-related sensations . Aerobic exercise has been shown to reduce generalized anxiety , and may also reduce anxiety sensitivity through exposure to feared physiological sensations . Accordingly , 54 participants with elevated anxiety sensitivity scores completed six 20-min treadmill exercise sessions at either a high-intensity aerobic ( n = 29 ) or low-intensity ( n = 25 ) level . Self-ratings of anxiety sensitivity , fear of physiological sensations associated with anxiety , and generalized anxiety were obtained at pre-treatment , post-treatment , and one-week follow-up . Results indicated that both high- and low-intensity exercise reduced anxiety sensitivity . However , high-intensity exercise caused more rapid reductions in a global measure of anxiety sensitivity and produced more treatment responders than low-intensity exercise . Only high-intensity exercise reduced fear of anxiety-related bodily sensations . The implication s of these findings are discussed Escitalopram has been shown in clinical trials to improve anxiety symptoms associated with depression , panic disorder , and social anxiety disorder . This study was design ed to evaluate the efficacy and tolerability of escitalopram in the treatment of generalized anxiety disorder ( GAD ) . Out patients ( 18 years or older ) who met DSM-IV criteria for GAD , with baseline Hamilton Rating Scale for Anxiety ( HAMA ) scores > or = 18 , were r and omly assigned to double blind treatment with escitalopram ( 10 mg/day for the first 4 weeks and then flexibly dosed from 10 - 20 mg/day ) or placebo for 8 weeks , following a 1-week , single-blind , placebo lead-in period . The primary efficacy variable was the mean change from baseline in total HAMA score at Week 8 . The escitalopram group ( N = 158 ) showed a statistically significant , and clinical ly relevant , greater improvement at endpoint compared with placebo ( N = 157 ) in all prospect ively defined efficacy parameters . Significant improvement in HAMA total score and HAMA psychic anxiety subscale score for the escitalopram-treated group vs. the placebo-treated group was observed beginning at Week 1 and at each study visit thereafter . Mean changes from baseline to Week 8 on the HAMA total score using a last-observation-carried-forward ( LOCF ) approach were -11.3 for escitalopram and -7.4 for placebo ( P<.001 ) . Response rates at Week 8 were 68 % for escitalopram and 41 % for placebo ( P<.01 ) for completers , and 58 % for escitalopram and 38 % for placebo LOCF values ( P<.01 ) . Treatment with escitalopram was well tolerated , with low rates of reported adverse events and an incidence of discontinuation due to adverse events not statistically different from placebo ( 8.9 % vs. 5.1 % ; P=.27 ) . Escitalopram 10 - 20 mg/day is effective , safe , and well tolerated in the treatment of patients with GAD PURPOSE The purpose of this investigation was to examine selected psychobiological responses to acute bouts of resistance exercise ( RE ) of different intensities . METHODS Eighty-four participants were classified as experienced or inexperienced and then r and omly assigned to three conditions : 1 ) 50 % of one repetition maximum(1RM ) , 2 ) 80 % 1RM , or 3 ) control condition . RE consisted of performing three sets of four exercises between 12 to 20 reps in the 50 % 1RM condition and four to eight reps in the 80 % 1RM condition . Dependent variables consisted of state anxiety ( SA ) , mood states ( POMS ) , systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate ( HR ) . These variables were assessed before as well as 1 , 20 , 60 , 120 , and 180-min following the conditions . Data were analyzed with a 2 ( experience ) x 3 ( conditions ) x 6 ( trials ) mixed model ANOVA and Tukey post-hoc tests . RESULTS Results indicated that SA decreased significantly ( P < 0.05 ) 180 min following the 50 % 1RM condition . A significant decrease ( P < 0.05 ) in vigor occurred immediately following the 50 % IRM condition and persisted for 20 min . SBP increased significantly ( P < 0.05 ) immediately following the 80 % 1RM condition . HR increased significantly ( P < 0.05 ) following both RE conditions . No significant differences were found between the experienced or inexperienced participants . CONCLUSIONS An acute bout of RE at 50 % 1RM is associated with an immediate reduction in vigor followed by a significant decrease in SA that emerged 180 min following exercise Blunted neuroendocrine and physiological responses to the selective 5-HT(1A ) receptor agonist , ipsapirone , have been observed in patients with panic disorder and /or agoraphobia ( PDA ) . In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions , challenges with an oral dose of ipsapirone ( 0.3 mg/kg ) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine , aerobic exercise and placebo . Before treatment , administration of ipsapirone was followed by significant increases of cortisol , anxiety and other psychopathological symptoms in comparison to the placebo challenge . In addition , a significant decrease of body temperature was observed . After the 10-week treatment period , the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group . In contrast , there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment . The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment . In conclusion , our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological , neuroendocrine and temperature responses to ipsapirone CONTEXT Yoga is increasing in popularity , with an estimated 15 million practitioners in the United States , yet there is a dearth of empirical data addressing the holistic benefits of yoga . OBJECTIVE To compare the physical and mental benefits of an exercise-based yoga practice to that of a more comprehensive yoga practice ( one with an ethical/spiritual component ) . DESIGN Students with mild to moderate depression , anxiety , or stress and who agreed to participate were assigned to one of three groups : integrated yoga , yoga as exercise , control . PARTICIPANTS A total of 81 undergraduate students 18 years and older at a university in the southeastern United States participated in the study . MAIN OUTCOME MEASURES Depression , anxiety , stress , hope , and salivary cortisol . RESULTS Over time , participants in both the integrated and exercise yoga groups experienced decreased depression and stress , an increased sense of hopefulness , and increased flexibility compared to the control group . However , only the integrated yoga group experienced decreased anxiety-related symptoms and decreased salivary cortisol from the beginning to the end of the study . CONCLUSIONS Yoga , practice d in a more integrated form , ie , with an ethical and spiritual component , may provide additional benefits over yoga practice d as an exercise regimen OBJECTIVE The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo . METHOD Forty-six out patients suffering from moderate to severe panic disorder with or without agoraphobia ( DSM-III-R criteria ) were r and omly assigned to a 10-week treatment protocol of regular aerobic exercise ( running ) , clomipramine ( 112.5 mg/day ) , or placebo pills . RESULTS The dropout rate was 31 % for the exercise group , 27 % for the placebo group , and 0 % for the clomipramine group . In comparison with placebo , both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures ( analysis of variance , last-observation-carried-forward method and completer analysis ) . A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively . Depressive symptoms were also significantly improved by exercise and clomipramine treatment . CONCLUSIONS These results suggest that regular aerobic exercise alone , in comparison with placebo , is associated with significant clinical improvement in patients suffering from panic disorder , but that it is less effective than treatment with clomipramine Two experiments were conducted to investigate the effect of resistance exercise on state anxiety . In experiment 1 , participants engaged in three 20-min bouts of resistance exercise , with intensity set as a function of perceived exertion . Results indicated that the relationship between resistance exercise and anxiety was moderated by both exercise intensity and gender . Although females reported no change in anxiety , males reported an increase in anxietyfollowing moderate and high-intensity exercise , and a decrease in anxiety following low intensity exercise . Experiment 2 was design ed to replicate these findings utilizing a more precise manipulation of exercise intensity . Results indicated that the change in anxiety was again moderated by exercise intensity but was unaffected by gender . Both males and females reported increases in anxiety following 20 min of high-intensity exercise ( 75 - 85 % of 1 RM ) , as well as significant decreases in anxiety following low-intensity exercise ( 40 - 50 % of 1 RM ) The impact of high levels of psychological stress symptoms in the hospital after an acute myocardial infa rct ion ( AMI ) was examined over 5 years among 461 men who took part in a trial of psychological stress monitoring and intervention . Psychological stress was assessed using the 20-item General Health Question naire ( GHQ ) 1 to 2 days before hospital discharge . Once discharged , patients in the treatment group responded to the GHQ by telephone on a monthly basis and , when they reported high levels of stress symptoms ( GHQ greater than or equal to 5 ) , received visits from nurses to help them deal with their life problems . Control patients received routine medical care after discharge . Post-hoc subgroup analyses based on life-table methods showed that , for patients receiving routine care after discharge , high stress ( GHQ greater than or equal to 5 ) was associated with a close to threefold increase in risk of cardiac mortality over 5 years ( p = 0.0003 ) and an approximately 1.5-fold increase in risk of reinfa rct ion over the same period ( p = 0.09 ) . In contrast , highly stressed patients who took part in the 1-year program of stress monitoring and intervention did not experience any significant long-term increase in risk . Although program impact was significant in terms of reduction of both cardiac mortality ( p = 0.006 ) and AMI recurrences ( p = 0.004 ) among highly stressed patients , there was little evidence of impact among patients with low levels of stress in the hospital . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The purpose of this study was to contrast state anxiety responses to acute aerobic and resistance exercise across an 8-week period . METHODS State anxiety ( STAI-Y1 ) was assessed immediately prior to and 5 min following 50-min exercise sessions in 42 adults enrolled in introductory level resistance training or step aerobic exercise classes . Participants were instructed to maintain an intensity between 70 - 80 % of their own maximum in both exercise conditions . State anxiety was assessed at weeks one , four and eight of 16-week courses . RESULTS Repeated measures ANOVA revealed that state anxiety decreased ( p<0.05 ) following both exercise conditions ( step aerobics : 36.65 to 33.03 ; resistance training : 35.12 to 30.39 ) . The magnitude of the reduction did not differ significantly between conditions , nor did it change from week one to week eight . Participants were grouped into high and low baseline state anxiety groups to determine the potential influence of baseline anxiety . Reductions ( p<0.05 ) in state anxiety were observed for the high baseline groups ( step aerobics : 49.7 to 40.4 ; resistance : 47.6 to 38.5 ) , and following step aerobic exercise for the low baseline group ( 29.9 to 26.8 ) . However , state anxiety did not decrease ( 29.6 to 29.5 ) following resistance exercise in the low baseline group . CONCLUSIONS These results indicate state anxiety reductions occur following 50-min of aerobic exercise or weight training , and responses were not altered across 8-weeks of training . Similar state anxiety reductions were observed for each exercise mode in cases with elevated baseline state anxiety values , low baseline state anxiety levels were significantly reduced solely in the step aerobics condition BACKGROUND Chronic exercise has been shown to have therapeutic effects in panic disorder ( PD ) . The mechanism of these effects is unknown . Acute exercise reduces the effect of a panic challenge in healthy volunteers . Such an effect has not yet been demonstrated in PD patients . The present study aim ed at exploring the antipanic effects of acute exercise on a 35 % CO2 panic provocation in treatment-naïve PD patients to further eluci date the mechanisms of the beneficial effects of exercise on panic . METHODS Eighteen PD patients performed either moderate/hard exercise or very-light exercise before a 35 % CO2 challenge in a r and omized , between-group design . The reactivity to CO2 was assessed with the Visual Analogue Anxiety Scale and the DSM-IV Panic Symptom List . RESULTS Panic reactions to CO2 were smaller in patients that performed moderate/hard exercise in contrast to those that performed very-light exercise . Increments in both measurements and panic rates were consistently reduced by intense exercise . LIMITATIONS Since this study focuses on the acute effects of exercise on CO2 sensitivity in patients with PD , the results of repetitive exercise sessions on the rate of spontaneous panic attacks and overall symptoms are warranted . The small sample size and other limitations are addressed . CONCLUSIONS Exercise reduced the panicogenic effects of a CO2 challenge . In addition to its therapeutic potential , exercise may also be useful as a laboratory maneuver with heuristic value in experimental research into the mechanisms of antipanic treatment Following an acute myocardial infa rct ion , evaluation of a patient 's own perceptions of health , including mood state , provides useful information about the efficacy of rehabilitation when data are available for patients r and omized to both control and intervention . Data are presented on the Profile of Mood States ( POMS ) in 187 patients , with mild to moderate scores for Spielberger state anxiety and /or Beck depression , who were r and omized within 6 wk of acute myocardial infa rct ion to usual care or to brief cardiac rehabilitation lasting 8 wk and who were followed-up during the 12 months following the acute event . Repeated measures multivariate analysis of covariance identified significant main as well as time effects in POMS scores over 12 months . Repeated measures analysis of variance over the 12 months demonstrated significant improvement for both depression and anxiety in both groups . At 8 wk , improvement was greater in the rehabilitation patients than usual care patients but only in the tension-anxiety , depression-dejection and vigor-activity dimensions of POMS and only in anxiety in those patients with above mean anxiety scores . Overall , rehabilitation and control patients showed similar and significant improvements in anxiety , depression and in mood states over the duration of the 12-month trial AIM AND OBJECTIVE To evaluate the influence of an exercise programme on postmenopausal women with symptoms of anxiety and depression . BACKGROUND The menopause is a period of hormonal changes when mood variations are probably more severe than at any other period of women 's lives . DESIGN Prospect i ve study with control group and pre- and post-treatment measures , after six months treatment . Conducted at two healthcare clinics , in the province of Granada ( Spain ) . METHODS A convenience sample of 60 postmenopausal women aged 60 - 70 years , with symptoms of depression and anxiety , was recruited . The women were r and omly divided into two groups : ( 1 ) control group , no treatment ( n = 30 ) ; ( 2 ) exercise group , which carried out a programme of mixed physical exercises with musical support ( n = 30 ) . All subjects answered question naires for the Hamilton Anxiety Scale and the Brink and Yesavage Geriatric Depression Scale before and after treatment . RESULTS In the exercise group , statistically significant improvements were observed in subjects with moderate and severe depression ( 18 and 22 % , respectively ) and in those with symptoms of anxiety . No such changes were observed in the control group . CONCLUSIONS A controlled programme of physical exercise for postmenopausal women alleviates symptoms of anxiety and depression , and its inclusion in primary healthcare programmes should be considered . RELEVANCE TO CLINICAL PRACTICE Menopausal women may benefit from physical exercise , which attenuates the effects of the physiological and psychological changes associated with the menopause and prevents pathologic changes BACKGROUND A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia , the Panic and Agoraphobia Scale ( P & A ) . The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients ( panic attacks , avoidance , anticipatory anxiety , disability and worries about health ) . The application of this scale in a double-blind placebo-controlled panic disorder trial is described . At the same time , the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy . METHODS Patients with Panic disorder ( DSM-IV ) were r and omly assigned to three treatment modalities : running ( n=45 ) , clomipramine ( n=15 ) or placebo ( n=15 ) . Treatment efficacy was measured with the Panic and Agoraphobia Scale ( P & A ) and other rating scales . RESULTS According to the P & A and other scales , both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment . Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise . The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability . CONCLUSIONS The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments . Analysis of the scales five subscores may help to underst and mechanisms of action of panic disorder treatments OBJECTIVES This study examined the effect of anxiety on mortality and nonfatal myocardial infa rct ion ( MI ) in patients with coronary artery disease ( CAD ) . BACKGROUND Inconsistent data exist regarding the impact of anxiety on the prognosis of patients with CAD . METHODS The authors conducted a prospect i ve cohort study at an outpatient cardiology clinic of 516 patients with CAD ( mean age 68 years at entry , 82 % male ) by administering the Kellner Symptom Question naire annually . The primary outcome was the composite of nonfatal MI or all-cause mortality . RESULTS During an average follow-up of 3.4 years , we documented 44 nonfatal MIs and 19 deaths . A high cumulative anxiety score was associated with an increased risk of nonfatal MI or death . Comparing the highest to lowest tertile of anxiety score , the age-adjusted hazard ratio was 1.97 ( 95 % confidence interval 1.03 to 3.78 , p = 0.04 ) . In a multivariate Cox model after adjusting for age , gender , education , marital status , smoking , hypertension , diabetes mellitus , previous MI , body mass index , and total cholesterol , each unit increase in the cumulative mean anxiety score was associated with increased risk of nonfatal MI or total mortality ; the hazard ratio was 1.06 ( 95 % confidence interval 1.01 to 1.12 , p = 0.02 ) . CONCLUSIONS A high level of anxiety maintained after CAD diagnosis constitutes a strong risk of MI or death among patients with CAD This investigation was design ed to determine the impact of a brief period of cardiac rehabilitation , initiated within 6 weeks of acute myocardial infa rct ion ( AMI ) , on both disease-specific and generic health-related quality of life , exercise tolerance and return to work after AMI . With a stratified , parallel group design , 201 low-risk patients with evidence of depression or anxiety , or both , after AMI , were r and omized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care . Although the differences were small , significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific , health-related Quality of Life Question naire , in their state of anxiety and in exercise tolerance . All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period . However , the 95 % confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained , clinical ly important benefits of rehabilitation in disease-specific ( limitations , -2.70 , 1.40 ; emotions , -4.86 , 1.10 , where negative values favor conventional care and positive values favor rehabilitation ) and generic health-related quality of life ( time trade-off , -0.062 , 0.052 ; quality of well-being , -0.042 , 0.035 ) or in exercise tolerance ( -38.5 , 52.1 kpm/min ) ; also , return to work was similar in the 2 groups ( relative risk , 0.93 ; confidence interval , 0.71 , 1.64 ) . ( ABSTRACT TRUNCATED AT 250 WORDS 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 . Objective : To explore the long-term effect of anxiety and depression on outcome after cardiac surgery . To date , the relationship between psychosocial factors and future cardiac events has been investigated mainly in population -based studies , in patients after cardiac catheterization or myocardial infa rct ion . Methods : In total , 180 patients who underwent cardiac surgery using cardiopulmonary bypass were prospect ively studied and followed up for 4 years . Anxiety ( Spielberger State-Trait Anxiety Inventory , STAI-S/STAI-T ) , depression ( Beck Depression Inventory , BDI ) , living alone , and education level along with clinical risk factors and perioperative characteristics were assessed . Psychological self-report question naires were completed preoperatively and 6 , 12 , 24 , 36 , and 48 months after discharge . Clinical end-points were mortality and cardiac events requiring hospitalization during follow-up . Results : Average preoperative STAI-T score was 44.6 ± 10 . Kaplan-Meier analysis showed a significant effect of preoperative STAI-T > 45 points ( p = .008 ) on mortality . In multivariate models , postoperative congestive heart failure ( OR : 10.8 ; 95 % confidence interval [CI]:2.9–40.1 ; p = .009 ) and preoperative STAI-T ( score OR : 1.07 ; 95 % CI : 1.01–1.15 ; p = .05 ) were independently associated with mortality . The occurrence of cardiovascular hospitalization was independently associated with postoperative intensive care unit days ( OR : 1.41 ; 95 % CI : 1.01–1.96 ; p = .045 ) and post discharge 6th month STAI-T ( OR : 1.06 ; 95 % CI:1.01–1.13 ; p = .03 ) . Conclusions : The results of the present study suggest that the assessment of psychosocial factors , particularly the ongoing assessment of anxiety , could help in risk stratification and identification of patients at risk of mortality and cardiovascular morbidity after cardiac surgery . BDI = Beck Depression Inventory ; STAI-S = state anxiety subscale ; STAI-T = trait anxiety subscale of Spielberger State-Trait Anxiety Inventory ; CPB = cardiopulmonary bypass ; CABG = coronary artery bypass grafting ; CHF = congestive heart failure ; CHD = coronary heart disease ; ICU = intensive care unit ; MI = myocardial infa rct ion ; PTSD = posttraumatic stress disorder Anxiety sensitivity ( AS ) is the fear of anxiety-related sensations . According to Reiss 's ( e.g. , Reiss , 1991 ) expectancy theory , AS amplifies fear and anxiety reactions , and plays an important role in the etiology and maintenance of anxiety disorders , particularly panic disorder . Recent evidence suggests that AS has a hierarchical structure , consisting of multiple lower order factors , loading on a single higher order factor . If each factor corresponds to a discrete mechanism ( Cattell , 1978 ) , then the results suggest that AS arises from a hierarchic arrangement of mechanisms . A problem with previous studies is that they were based on the 16-item Anxiety Sensitivity Index , which may not contain enough items to reveal the type and number of lower order factors . Also , some of the original ASI items are too general to assess specific , lower order factors . Accordingly , we developed an exp and ed measure of AS -- the ASI-R -- which consists of 36 items with subscales assessing each of the major domains of AS suggested by previous studies . The ASI-R was completed by 155 psychiatric out patients . Factor analyses indicated a four-factor hierarchical solution , consisting of four lower order factors , loading on a single higher factor . The lower order factors were : ( 1 ) fear of respiratory symptoms , ( 2 ) fear of publicly observable anxiety reactions , ( 3 ) fear of cardiovascular symptoms , and ( 4 ) fear of cognitive dyscontrol . Each factor was correlated with measures of anxiety and depression , and fear of cognitive dyscontrol was most highly correlated with depression , which is broadly consistent with previous research . At pretreatment , patients with panic disorder tended to scored highest on each of the factors , compared to patients with other anxiety disorders and those with nonanxiety disorders . These findings offer further evidence that Reiss 's expectancy theory would benefit from revision , to incorporate the notion of a hierarchic structure of AS The 12-month effects of exercise training on psychological outcomes in adults ages 50 - 65 years were evaluated . Ss ( N = 357 ) were r and omly assigned to assessment -only control or to higher intensity group , higher intensity home , or lower intensity home exercise training . Exercisers showed reductions in perceived stress and anxiety in relation to controls ( p < .04 ) . Reductions in stress were particularly notable in smokers . Regardless of program assignment , greater exercise participation was significantly related to less anxiety and fewer depressive symptoms , independent of changes in fitness or body weight ( p < .05 ) . It was concluded that neither a group format nor vigorous activity was essential in attaining psychological benefits from exercise training in healthy adults Abstract Objectives . Regular aerobic exercise ( running ) has been shown to be superior to a pill placebo in the treatment of panic disorder . Combined drug and exercise treatment has not been investigated in r and omized controlled studies to date . Methods . This is a r and omized , 10-week , controlled , parallel group , pilot study . A total of 75 out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 ) received either ( 1 ) exercise plus paroxetine 40 mg/day ( n=21 ) , ( 2 ) relaxation plus paroxetine ( n=17 ) , ( 3 ) exercise plus pill placebo ( n=20 ) , or ( 4 ) relaxation plus pill placebo ( n=17 ) . Changes in the Panic and Agoraphobia Scale ( P&A ) , and the Clinical Global Impression Scale ( CGI ) underwent repeated measure analysis . Results . Effects sizes were large for all groups ( d=1.53–3.87 ) , however not significantly different . Paroxetine-treated patients were significantly more improved than placebo-treated patients . On the CGI , patients in the exercise groups ( plus paroxetine or placebo ) had a trend toward better improvement compared to relaxation ( P=0.06 ) . Response and remission rates were higher in the paroxetine compared to pill placebo groups . Conclusions . While paroxetine was superior to placebo , aerobic exercise did not differ from relaxation training in most efficacy measures BACKGROUND Treated anxiety increased in the UK by over 30 % since 1994 . Medication and psychological treatment is most common , but outcomes are sometimes poor , with high relapse rates . Lifestyle has a potential role in treatment , but is not considered in clinical guidelines . Panic disorder is potentially influenced by lifestyle factors . METHODS 16 week unblinded pragmatic r and omised controlled trial in 15 East of Engl and primary care practice s ( 2 Primary Care Trusts ) . Participants met DSM-IV criteria for panic disorder with/without agoraphobia . Follow-up at 20 weeks and 10 months . Control arm , unrestricted routine GP care . Trial Arm , Occupational therapy-led lifestyle treatment comprising : lifestyle review of fluid intake , diet pattern , exercise , caffeine , alcohol and nicotine ; negotiation of positive lifestyle changes ; monitoring and review of impact of changes . PRIMARY OUTCOME MEASURE Beck Anxiety Inventory . DATA ANALYSIS Intention-to-treat analysis provided between-group comparisons using analysis of co-variance . Bonferroni method to adjust p-values . RESULTS From 199 referrals , 36 GP care and 31 lifestyle arm patients completed to final follow-up . Significantly lower lifestyle arm BAI scores at 20 weeks ( p<0.001 ) , non-significant ( p=0.167 ) at 10 months after Bonferroni correction . 63.6 % lifestyle arm , and 40 % GP arm patients ( p=0.045 ) panic-free at 20 weeks ; 67.7 % and 48.5 % ( p=0.123 ) respectively at 10 months . LIMITATIONS Final study size/power calls for caution in interpreting findings . CONCLUSIONS A lifestyle approach may provide a clinical ly effective intervention at least as effective as routine GP care , with significant improvements in anxiety compared with routine GP care at the end of treatment . Further study is required before suggesting practice changes BACKGROUND Exercise interventions repeatedly have been shown to be efficacious for the treatment of depression , and initial studies indicate similar efficacy for the treatment of anxiety conditions . To further study the potential beneficial role of prescriptive exercise for anxiety-related conditions , we examined the role of exercise in reducing fears of anxiety-related sensations ( anxiety sensitivity ) . METHODS We r and omly assigned 60 participants with elevated levels of anxiety sensitivity to a 2-week exercise intervention , a 2-week exercise plus cognitive restructuring intervention , or a waitlist control condition . Assessment of outcome was completed at pretreatment , midtreatment , 1-week posttreatment , and 3-week follow-up . RESULTS We found that both exercise conditions led to clinical ly significant changes in anxiety sensitivity that were superior to the waitlist condition , representing a large controlled effect size ( d=2.15 ) . Adding a cognitive component did not facilitate the effects of the exercise intervention . Consistent with hypotheses , changes in anxiety sensitivity mediated the beneficial effects of exercise on anxious and depressed mood . CONCLUSIONS We discuss these findings in terms of the potential role of exercise as an additional psychosocial intervention for conditions such as panic disorder , where anxiety sensitivity is a prominent component of pathology INTRODUCTION Data on basal hypothalamo-pituitary-adrenomedullary ( HPA ) function over controlled treatment trials with serotonergic drugs in anxiety disorders are still rare . METHODS 29 patients with panic disorder participating in a 10 week r and omized , controlled trial ( paroxetine vs. placebo with exercise or relaxation ; N=60 ) collected urine for cortisol excretion over 3 consecutive nights before start and before termination of the treatment episode . Urinary cortisol was measured by radioimmunoassay . Efficacy measures were the Clinical Global Impression Scale ( CGI ) and the Panic and Agoraphobia Scale ( P&A ) . 83 % were female ( p<.05 vs. males ) . 55 % received additional aerobic exercise , and 45 % relaxation . 55 % received paroxetine treatment , and 45 % placebo . Significantly fewer males received placebo treatment ( p<.05 ) . RESULTS All subjects improved significantly . Cortisol excretion did not differ between treatment groups or at pre-/post measurements . Females showed a significantly higher variability of cortisol excretion compared to males , at pre-(p<.005 ) and post ( p=.015 ) assessment s. Males displayed a trend to lower basal HPA function at end of treatment ( p=.08 ) . HPA variability after treatment showed a trend to be higher in the paroxetine ( p=.052 ) -who clinical ly improved significantly better- compared to the placebo group . No relationship between HPA activity and treatment response or with exercise was detected . DISCUSSION HPA function shows significant gender differences , with females having a higher HPA function variability . Future studies on HPA function in treatment trials should address gender and medication effects 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 Background The Wales National Exercise Referral Scheme ( NERS ) is a 16-week programme including motivational interviewing , goal setting and relapse prevention . Method A pragmatic r and omised controlled trial with nested economic evaluation of 2160 inactive participants with coronary heart disease risk ( CHD , 1559 , 72 % ) , mild to moderate depression , anxiety or stress ( 79 , 4 % ) or both ( 522 , 24 % ) r and omised to receive ( 1 ) NERS or ( 2 ) normal care and brief written information . Outcome measures at 12 months included the 7-day physical activity recall , the hospital anxiety and depression scale . Results Ordinal regression identified increased physical activity among those r and omised to NERS compared with those receiving normal care in all participants ( OR 1.19 , 95 % CI 0.99 to 1.43 ) , and among those referred for CHD only ( OR 1.29 , 95 % CI 1.04 to 1.60 ) . For those referred for mental health reason alone , or in combination with CHD , there were significantly lower levels of anxiety ( OR −1.56 , 95 % CI −2.75 to −0.38 ) and depression ( OR −1.39 , 95 % CI −2.60 to −0.18 ) , but no effect on physical activity . The base-case incremental cost-effectiveness ratio was £ 12 111 per quality adjusted life year , falling to £ 9741 if participants were to contribute £ 2 per session . Conclusions NERS was effective in increasing physical activity among those referred for CHD risk only . Among mental health referrals , NERS did not influence physical activity but was associated with reduced anxiety and depression . Effects were dependent on adherence . NERS is likely to be cost effective with respect to prevailing payer thresholds . Trial registration Current Controlled Trials IS RCT N47680448 This study investigated a possible relationship between exercise intensity and mood alteration that commonly is associated with physical activity . 91 college students completed the Profile of Mood States before and after 20 min . of jogging at three intensities : 55 % , 75 % , and 79 % of age-adjusted maximum heart rate on different occasions . Exercisers also completed a demographic inventory , a Lie Scale , and the State-Trait Anxiety Inventory . Contrary to our expectations , the interaction between exercise intensity and pre-post mood benefits was not significant . Supporting the manipulation of exercise intensity , the univariate interaction between exercise intensity and pre-post exercise scores on Fatigue was significant . Joggers reported short-term mood benefits on the combined subscales of the Profile of Mood States , and each subscale contributed to the benefits . Thus , regardless of the low- or moderate-intensity , participants reported that they “ felt better ” after exercising ISSUE ADDRESSED To assess the adherence and acceptability of a physical activity program delivered as an adjunct to the usual cognitive behavioural group therapy ( CBGT ) for adults with anxiety disorders . METHODS Seventy-three participants with either a generalised anxiety disorder , social phobia or panic disorder were r and omised to either exercise-enhanced CBGT ( CBGT+EX ) or the usual CBGT plus nutrition education ( CBGT+ED ) group . Physical activity , stress , anxiety , depression were assessed at baseline ; session attendance , compliance and satisfaction were assessed during the eight-week intervention . RESULTS Forty-five per cent of participants achieved the recommended levels of physical activity for health at baseline . The proportions of participants attending group meetings declined over time across both groups . In the intervention groups ( CBGT+EX ) , a slightly higher proportion of participants attended the CBGT session than the physical activity sessions . Individuals with social phobia were significantly more likely than those with panic or generalised anxiety disorder to adhere to the physical activity program . Among the remaining adherers , most reported satisfaction with their skills development and better underst and ing of the benefits of physical activity . CONCLUSIONS Time constraints and participants viewing physical activities as irrelevant or detracting them from their psychological treatment are potential factors contributing to low adherence and present as challenges in implementing a physical activity program as adjunctive to psychological treatment . Process evaluation data helped profile participants who adhered or not adhered to the physical activity program and will inform future physical activity promotion to individuals with anxiety disorders BACKGROUND This study , conducted between 1998 and 2001 and analyzed in 2002 and 2003 , was design ed to test ( 1 ) whether exercise is an efficacious treatment for mild to moderate major depressive disorder ( MDD ) , and ( 2 ) the dose-response relation of exercise and reduction in depressive symptoms . DESIGN The study was a r and omized 2x2 factorial design , plus placebo control . SETTING / PARTICIPANTS All exercise was performed in a supervised laboratory setting with adults ( n = 80 ) aged 20 to 45 years diagnosed with mild to moderate MDD . INTERVENTION Participants were r and omized to one of four aerobic exercise treatment groups that varied total energy expenditure ( 7.0 kcal/kg/week or 17.5 kcal/kg/week ) and frequency ( 3 days/week or 5 days/week ) or to exercise placebo control ( 3 days/week flexibility exercise ) . The 17.5-kcal/kg/week dose is consistent with public health recommendations for physical activity and was termed " public health dose " ( PHD ) . The 7.0-kcal/kg/week dose was termed " low dose " ( LD ) . MAIN OUTCOME MEASURES The primary outcome was the score on the 17-item Hamilton Rating Scale for Depression ( HRSD(17 ) ) . RESULTS The main effect of energy expenditure in reducing HRSD(17 ) scores at 12 weeks was significant . Adjusted mean HRSD(17 ) scores at 12 weeks were reduced 47 % from baseline for PHD , compared with 30 % for LD and 29 % for control . There was no main effect of exercise frequency at 12 weeks . CONCLUSIONS Aerobic exercise at a dose consistent with public health recommendations is an effective treatment for MDD of mild to moderate severity . A lower dose is comparable to placebo effect OBJECTIVES The purpose of this study was to investigate the long-term cardiac effects of depression and anxiety assessed at a young age , when reverse causation is not feasible . BACKGROUND Most prospect i ve studies found a relatively strong association between depression and subsequent coronary heart disease ( CHD ) . However , almost exclusively , only middle-age or older participants were examined , and sub clinical atherosclerosis might contribute to the observed association . The prospect i ve association between anxiety and CHD was less evident in previous studies and has been subjected to similar method ological concerns on the possibility for a reverse causation . METHODS In a nationwide survey , 49,321 young Swedish men , 18 to 20 years of age , were medically examined for military service in 1969 and 1970 . All the conscripts were seen by a psychologist for a structured interview . Conscripts reporting or presenting any psychiatric symptoms were seen by psychiatrists . Depression and anxiety was diagnosed according to International Classification of Diseases-8th Revision ( ICD-8 ) . Data on well-established CHD risk factors and potential confounders were also collected ( i.e. , anthropometrics , diabetes , blood pressure , smoking , alcohol consumption , physical activity , socioeconomic position , family history of CHD , and geographic area ) . Participants were followed for CHD and for acute myocardial infa rct ion for 37 years . RESULTS Multiadjusted hazard ratios associated with depression were 1.04 ( 95 % confidence interval [ CI ] : 0.70 to 1.54 ) , 1.03 ( 95 % CI : 0.65 to 1.65 ) , for CHD and for acute myocardial infa rct ion , respectively . The corresponding multiadjusted hazard ratios for anxiety were 2.17 ( 95 % CI : 1.28 to 3.67 ) and 2.51 ( 95 % CI : 1.38 to 4.55 ) . CONCLUSIONS In men , aged 18 to 20 years , anxiety as diagnosed by experts according to ICD-8 criteria independently predicted subsequent CHD events . In contrast , we found no support for such an effect concerning early-onset depression in men 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 |
2,326 | 29,575,031 | Parental responsivity is the only parenting axis strongly associated with both improved child cognition and behaviour .
Parental dem and ingness is associated only with improved child cognition , and parental warmth and rejection are associated only with child behaviour .
Parental coercion is not associated with subsequent child outcomes .
Parental responsivity may be essential in optimizing neurodevelopment in former preterm infants . | We sought to evaluate published evidence in aggregate regarding the impact of parenting style on the cognitive and behavioural outcomes of former preterm infants . | Background Preterm-born or asphyxiated term-born children who received neonatal intensive care show more emotional and behavioral problems than term-born children without a medical condition . It is uncertain whether regular parenting intervention programs to which the parents of these children are usually referred , are effective in reducing child problem behavior in this specific population . Our objective was to investigate whether a regular , brief parenting intervention , Primary Care Triple P , is effective in decreasing emotional and behavioral problems in preterm-born or asphyxiated term-born preschoolers . Methods For this pragmatic , open r and omized clinical trial , participants were recruited from a cohort of infants admitted to the neonatal intensive care units ( NICU ) of two Dutch hospitals . Children born with a gestational age < 32 weeks or birth weight < 1500 g and children born at a gestational age 37–42 weeks with perinatal asphyxia were included . After screening for a t-score ≥60 on the Child Behavior Checklist ( CBCL ) , children were r and omly assigned to Primary Care Triple P ( n = 34 ) or a wait-list control group ( n = 33 ) . The primary outcome was child emotional and behavioral problems reported by parents on the CBCL , 6 months after the start of the trial . Results There was no effect of the intervention on the CBCL at the trial endpoint ( t64 = 0.54 , P = .30 ) . On secondary measurements of child problem behavior , parenting style , parenting stress , and parent perceived child vulnerability , groups either did not differ significantly or the intervention group showed more problems . In both the intervention and control group there was a significant decrease in emotional and behavioral problems during the trial . Conclusions Primary Care Triple P , a brief parenting intervention , is not effective in reducing child emotional and behavioral problems in preterm-born children or term-born children with perinatal asphyxia . Trial registration Netherl and s National Trial Register ( NTR ) : OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : To examine the language development at corrected age 4 years of a regionally representative cohort of children born very preterm ( VPT ) . Of particular interest was the identification of biological and socioenvironmental risk and protective factors that influence VPT children 's early language development . Method : Data were collected as part of a prospect i ve longitudinal study of 110 VPT ( VPT : ≤33 weeks gestation ) and 113 full-term children ( full term : 37–41 weeks gestation ) born in Canterbury , New Zeal and from 1998 to 2000 . At corrected age 4 years , all children were assessed with the preschool version of the Clinical Evaluation of Language Fundamentals . Extensive information was also collected about children 's family social background , perinatal health , childrearing environment , education/intervention exposures , and neurodevelopmental progress from birth to age 4 . Results : At the age of 4 years , VPT children were characterized by poorer receptive and expressive language development than full-term children . These differences persisted after exclusion of children with neurosensory impairment as well as statistical adjustment for the effects of social risk . Within the VPT group , the key predictors of children 's overall language development were family social risk at birth ( p = .05 ) , severity of white matter abnormalities on neonatal magnetic resonance imaging ( p = .49 ) , observed parent-child synchrony ( p = .001 ) , and concurrent child cognitive ability ( p = .001 ) . Together , these factors accounted for 45 % of the variance in children 's total Clinical Evaluation of Language Fundamentals — Preschool scores . Conclusion : By preschool age , children born VPT show early emerging mild to moderate language delays that are likely to affect their school success and longer-term developmental progress . Findings highlight the importance of potentially modifiable factors such as early brain injury and parenting quality in predicting the language outcomes of children born VPT This study reports on child welfare outcomes of a community based , r and omized control trial of Promoting First Relationships ® ( PFR ; Kelly , S and oval , Zuckerman , & Buehlman , 2008 ) , a 10-week relationship-based home visiting program , on stability of children 's placements and permanency status two years after enrollment into the study . Toddlers 10 - 24 months ( N = 210 ) with a recent placement disruption were r and omized , along with their birth or foster/kin parents , to PFR ( n = 105 ) or a comparison condition ( n = 105 ) . A stable placement had no interruptions or disruptions . A permanent placement was a stable placement ending with a legal discharge to the study caregiver . Logistic regression models predicting the dichotomous stability and permanency variables , controlling for caregiver type , child welfare variables , and caregiver commitment , were conducted . There was no difference by intervention group on stability or permanency , but there was a significant interaction between caregiver type ( birth parent vs. foster/kin ) and intervention group . More foster/kin caregivers who received the PFR intervention provided stable , uninterrupted care and eventually adopted or became the legal guardians of the toddlers in their care , compared to foster/kin caregivers r and omized to the comparison condition The differential susceptibility to parenting model was examined in relation to toddler self-regulation in a prospect i ve longitudinal study of infants born preterm or low birth weight . We followed 153 mother-infant dyads across five time points between the infant 's Neonatal Intensive Care Unit stay and 24 months postterm . Assessment s of infant temperament , quality of early parenting interactions , context ual variables , and toddler effortful control and behavior problems were conducted . Results supported differential susceptibility and dual risk models in addition to documenting main effects of early parenting on children 's emerging self-regulation . Our data suggested that preterm or low birth weight infants who were prone to distress or rated by mothers as more difficult were particularly susceptible to the effects of early negative parenting OBJECTIVE . Although low birth weight premature infants and parents are at high risk for adverse health outcomes , there is a paucity of studies that test early NICU interventions with parents to prevent the development of negative parent-infant interaction trajectories and to reduce hospital length of stay . Our objective was to evaluate the efficacy of an educational-behavioral intervention program ( ie , Creating Opportunities for Parent Empowerment ) that was design ed to enhance parent-infant interactions and parent mental health outcomes for the ultimate purpose of improving child developmental and behavior outcomes . DESIGN , SETTING , AND PARTICIPANTS . A r and omized , controlled trial was conducted with 260 families with preterm infants from 2001 to 2004 in 2 NICUs in the northeast United States . Parents completed self-administered instruments during hospitalization , within 7 days after infant discharge , and at 2 months ' corrected age . Blinded observers rated parent-infant interactions in the NICU . INTERVENTION . All participants received 4 intervention sessions of audiotaped and written material s. Parents in the Creating Opportunities for Parent Empowerment program received information and behavioral activities about the appearance and behavioral characteristics of preterm infants and how best to parent them . The comparison intervention contained information regarding hospital services and policies . MAIN OUTCOME MEASURES . Parental stress , depression , anxiety , and beliefs ; parent-infant interaction during the NICU stay ; NICU length of stay ; and total hospitalization were measured . RESULTS . Mothers in the Creating Opportunities for Parent Empowerment program reported significantly less stress in the NICU and less depression and anxiety at 2 months ' corrected infant age than did comparison mothers . Blinded observers rated mothers and fathers in the Creating Opportunities for Parent Empowerment program as more positive in interactions with their infants . Mothers and fathers also reported stronger beliefs about their parental role and what behaviors and characteristics to expect of their infants during hospitalization . Infants in the Creating Opportunities for Parent Empowerment program had a 3.8-day shorter NICU length of stay ( mean : 31.86 vs 35.63 days ) and 3.9-day shorter total hospital length of stay ( mean : 35.29 vs 39.19 days ) than did comparison infants . CONCLUSIONS . A reproducible educational-behavioral intervention program for parents that commences early in the NICU can improve parent mental health outcomes , enhance parent-infant interaction , and reduce hospital length of stay ABSTRACT . We investigated the effects of a 1 -year home intervention on premature infants with low ( < 1500 g ) and higher ( 1500–2000 g ) birth weights . Infants from each weight condition were block r and omly assigned to a control or to one of two treatment groups . One treatment group focused on the development of the infant ; the other treatment group focused on the parent-infant interaction . The low birth weight infants obtained significantly lower Bayley mental and motor scores , and were more passive and less intense than the higher birth weight infants . However , the low birth weight infants and their parents were more responsive to the home intervention than were the higher birth weight infants , as demonstrated by changes in the Bayley mental scores and the Home Observation for Measurement of the Environment ( HOME ) inventory . These findings exemplify the reciprocal relationship between the child 's characteristics and parental responding . The importance of selecting the most high-risk premature infants for early home intervention is outlined The purpose of this pilot study was to evaluate the effectiveness of a parent-focused intervention program ( COPE ) on infant cognitive development and maternal coping . A r and omized clinical trial was conducted with 42 mothers of low-birth-weight ( LBW ) premature infants hospitalized in a neonatal intensive care unit ( NICU ) , with follow-up at 3 months ' and 6 months ' corrected ages . COPE mothers received the four-phase educational-behavioral program that began 2 - 4 days postbirth and continued through 1 week following discharge from the NICU . Comparison mothers received audiotaped information during the same four time frames . Results indicated that COPE infants had significantly higher mental development scores at a 3 months ' corrected age ( M = 100.3 ) than did the comparison infants ( M = 93.9 ) , and this difference widened at 6 months ' corrected age , with COPE infants scoring 14 points higher . COPE mothers were significantly less stressed by the NICU sights and sounds and had significantly stronger beliefs about what behaviors and characteristics to expect from their premature infants . Findings from this study support the need for further testing of early NICU interventions with parents to determine their effectiveness on parental coping and infant developmental outcomes OBJECTIVE Few studies exist that examine continuities between child and adult psychopathology in unselected sample s. This study prospect ively examined the adult outcomes of psychopathology in an epidemiological sample of children and adolescents across a 14-year period . METHOD In 1983 , parent ratings of behavioral and emotional problems were obtained for 1,578 children and adolescents aged 4 through 16 years from the Dutch general population . At follow-up , 14 years later , subjects were reassessed with a st and ardized DSM-IV interview . RESULTS High levels of childhood problems predicted an approximate 2- to 6-fold increased risk for adulthood DSM-IV diagnoses . The associations between specific childhood problems and adulthood diagnoses were complex . Social Problems in girls predicted later DSM-IV disorder . Rule-breaking behavior in boys predicted both mood disorders and disruptive disorders in adulthood . CONCLUSIONS High levels of childhood behavioral and emotional problems are related to DSM-IV diagnoses in adulthood . The strongest predictor of disorders in adulthood was childhood rule-breaking behavior . Attention Problems did not predict any of the DSM-IV categories when adjusted for the associations with other Child Behavior Checklist scales OBJECTIVES To assess the reliability of the Cochrane Risk of Bias ( ROB ) tool between individual raters and across consensus agreements of pairs of review ers and examine the impact of study -level factors on reliability . STUDY DESIGN AND SETTING Two review ers assessed risk of bias for 154 r and omized controlled trials ( RCTs ) . For 30 RCTs , two review ers from each of four centers assessed risk of bias and reached consensus . We assessed interrater agreement using kappas and the impact of study -level factors through subgroup analyses . RESULTS Reliability between two review ers was fair for most domains ( κ=0.24 - 0.37 ) , except sequence generation ( κ=0.79 , substantial ) . Reliability results across review er pairs : sequence generation , moderate ( κ=0.60 ) ; allocation concealment and " other sources of bias , " fair ( κ=0.37 - 0.27 ) ; and other domains , slight ( κ=0.05 - 0.09 ) . Reliability was influenced by the nature of the outcome , nature of the intervention , study design , trial hypothesis , and funding source . Variability result ed from different interpretation of the tool rather than different information identified in the study reports . CONCLUSION Low agreement has implication s for interpreting systematic review s. These findings suggest the need for detailed guidance in assessing the risk of bias We investigated the effects of a year-long home intervention with a sample of preterm infants r and omly assigned to 1 of 3 groups : a developmental intervention , a parent-infant intervention , and a no-treatment control group . A full-term no-treatment control was also used . Both intervention approaches focused on the parent-child unit , providing training for parents to improve observational skills , emotional support , and information about community re sources . However , whereas specific tasks to facilitate the child 's development were provided in the developmental intervention group , the quality of the parent-infant interaction was the target for treatment in the other group . All infants were assessed at 4 , 8 , 12 , and 16 months of age corrected for prematurity . The results suggest that although both intervention approaches were effective in modifying some aspects of the home environment and , to a lesser degree , in improving infants ' cognitive development , the parent-infant interaction approach seemed to have the greater impact . These findings confirm previous observations regarding the cognitive development of preterm and full-term infants during the first 18 months of life and demonstrate changes in behavior and behavior styles in both pre- and full-term infants as they become older The goal of current national and state legislation on welfare reform is to decrease the number of people who are dependent on public assistance , most of whom are mothers and their young children . Mothers ' patterns of welfare receipt in the 3 years following the birth of a child were examined vis-à-vis their associations with maternal emotional distress ( General Health Question naire ) , provision of learning experiences ( Home Observation of the Measurement of the Environment ) , parenting behavior , and the child 's cognitive test score ( Stanford-Binet ) in the third year of life . The data set was the Infant Health and Development Program , an eight-site r and omized clinical trial design ed to test the efficacy of educational and family support services in reducing developmental delays in low-birthweight , preterm infants ( N = 833 ) . Strong negative associations were found between receiving welfare and parenting behavior and child outcomes at age 3 years . Outcomes varied depending on when the mother received public assistance ( earlier or later in her child 's first 3 years ) and family poverty status on leaving welfare . The parenting behavior of mothers who had left welfare by their child 's third birthday was more likely to be authoritarian if she had left public assistance without also leaving poverty . Implication s of these findings for the well-being of children in low-income families are discussed OBJECTIVES To determine the efficacy of a neonatal parenting intervention for improving development in very preterm infants . STUDY DESIGN A cluster-r and omized , controlled trial with a cross-over design and washout period was conducted in 6 neonatal centers . Two hundred thirty-three babies < 32 weeks ' gestation were recruited ( intervention = 112 ; control = 121 ) . Intervention families received weekly Parent Baby Interaction Programme ( PBIP ) sessions during neonatal intensive care unit admission and up to 6 weeks after discharge . Control families received st and ard care . All 195 infants remaining in the study at 24 months ' corrected age were assessed by psychologists blinded to group allocation . RESULTS There was no significant difference in Mental Development Index ( -0.9 points ; 95 % CI , -5.0 , 3.2 ) or Psychomotor Development Index ( 2.5 ; -3.3 , 8.4 ) scores between the intervention and control groups and no significant effect of intervention on Mental Development Index or Psychomotor Development Index scores for subgroups dichotomized by gestational age ( < 28 weeks/ > or = 28 weeks ) , parity ( 1st/other child ) or mother 's cohabiting status ( supported/unsupported ) . CONCLUSIONS There was no effect of PBIP on infant development at 2 years ' corrected age . Parenting interventions may be better delivered after discharge or targeted for preterm infants with high biological and social risk Objective : To examine the initial efficacy of parent-child interaction therapy ( PCIT ) for treating behavior problems in young children who were born premature . Method : In this r and omized , controlled trial , 28 children between the ages of 18 and 60 months , who were born < 37 weeks gestation and presented with clinical ly significant externalizing behavior problems , were r and omly assigned to an immediate treatment ( IT ) or waitlist ( WL ) control group . Results : After 4 months , children who received PCIT were reported by their mother to have less attention problems , aggressive behaviors , and externalizing and internalizing behavior problems , and they were observed to be more compliant to maternal comm and s than children in the WL group . In addition , mothers in the IT group interacted more positively with their child , reported lower parenting stress related to difficult child behavior and demonstrated improved parenting practice s compared with WL mothers . Behavior change maintained for 80 % of the IT children 4 months after treatment completion . Conclusions : This study demonstrates preliminary efficacy of PCIT for the treatment of behavior problems in young children who were born premature |
2,327 | 25,537,979 | Conclusions High/iso SI on the HBP of Gd-EOB-DTPA-MRI is characteristic and a prevalent finding of FNHs and can be helpful in the management of patients with FNH.Key Points• The vast majority ( 94–97 % ) of FNHs show high/iso SI on HBP . •
High/iso SI on HBP was accurate for distinguishing FNH from hepatocellular adenoma . •
HBP of Gd-EOB-DTPA-MRI can reduce unnecessary biopsies for the diagnosis of FNHs | Abstract Objective We aim ed to systematic ally review the gadoxetic acid-enhanced magnetic resonance imaging ( Gd-EOB-DTPA-MRI ) findings of focal nodular hyperplasia ( FNH ) and its diagnostic value . | PURPOSE To compare the usefulness of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid ( Gd-EOB-DTPA ) and gadolinium diethylenetriaminepentaacetic acid ( Gd-DTPA ) in the diagnosis of focal liver lesions . MATERIAL S AND METHODS Thirty-one patients with focal liver lesions underwent T2- and T1-weighted spin-echo magnetic resonance ( MR ) imaging and fast low-angle shot two-dimensional MR imaging before , during , and after intravenous administration of three different doses of Gd-EOB-DTPA ( 12.5 , 25 , and 50 mumol per kilogram body weight ) . Gd-DTPA-enhanced imaging ( dose , 0.1 mmol per kilogram body weight ) was performed in the same patients within 1 week of Gd-EOB-DTPA imaging . RESULTS During the perfusion phase ( the 3 minutes after injection of contrast material ) , the dynamic enhancement characteristics seen after injection of 25 and 50 mumol of Gd-EOB-DTPA were similar to those seen with Gd-DTPA . At the lowest dose of Gd-EOB-DTPA ( 12.5 mumol ) , the dynamic enhancement characteristics were not comparable to those seen with Gd-DTPA . During the hepatobiliary phase ( 1.5 minutes to 4 hours after injection ) , Gd-EOB-DTPA-enhanced images yielded a dose-independent , statistically significant improvement in the detection rate of additional metastases , hepatocellular carcinomas , and hemangiomas compared with unenhanced and Gd-DTPA-enhanced images ( P < .05 ) . CONCLUSION Gd-EOB-DTPA-enhanced MR imaging enables improved detection of hepatic lesions over Gd-DTPA-enhanced MR imaging while providing comparable differential diagnostic information OBJECTIVE The purpose of this article is to prospect ively determine the sensitivity of hepatobiliary phase gadoxetate disodium-enhanced MRI combined with st and ard MRI in differentiating focal nodular hyperplasia ( FNH ) from hepatocellular adenoma ( HCA ) . SUBJECTS AND METHODS Patients suspected of having FNH or HCA larger than 2 cm underwent gadoxetate disodium-enhanced MRI . St and ard MRI was evaluated separately from the additional hepatobiliary phase by two blinded radiologists . For the largest lesion in each patient , findings were compared with histologic diagnosis . Sensitivity , positive predictive value ( PPV ) , and distinctive features were analyzed using McNemar and analysis of variance tests . RESULTS Fifty-two patients completed the study . Histologic diagnosis revealed 24 HCAs and 28 FNHs . Characterization on st and ard MRI was inconclusive in 40 % ( 21/52 ) and conclusive in 60 % ( 31/52 ) of lesions . The sensitivity of st and ard MRI for HCA was 50 % ( 12/24 ) with a PPV of 100 % ( 12/12 ) . The sensitivity for FNH was 68 % ( 19/28 ) with a PPV of 95 % ( 18/19 ) . After review of hepatobiliary phase , the sensitivity for HCA improved to 96 % ( 23/24 ) with a PPV of 96 % ( 23/24 ) . The sensitivity for FNH improved to 96 % ( 27/28 ) with a PPV of 96 % ( 27/28 ) . Features with significant predictive value for diagnosis in HCA included bleeding ( p < 0.001 ) , fat ( p = 0.010 ) , and glycogen ( p = 0.024 ) . The presence of a central scar was predictive for FNH ( p < 0.001 ) . CONCLUSION This study shows high sensitivity of gadoxetate disodium-enhanced MRI when st and ard series are combined with the hepatobiliary phase for differentiation of FNH and HCA in lesions larger than 2 cm PURPOSE To assess prospect ively the efficacy and safety of postcontrast magnetic resonance ( MR ) imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ( Gd-EOB-DTPA ) compared with that of precontrast MR imaging in patients who are known to have or are suspected of having liver lesions and who are scheduled for hepatic surgery . MATERIAL S AND METHODS Investigational review board approval and written informed consent were obtained . HIPAA went into effect after data collection . A total of 172 patients were enrolled . After precontrast MR imaging , 169 patients ( 94 men , 75 women ; mean age , 61 years ; age range , 19 - 84 years ) received an intravenous bolus of 25 micromol/kg Gd-EOB-DTPA and underwent dynamic gradient-recalled-echo and delayed MR imaging 20 minutes after injection . Arterial and portal phase computed tomography ( CT ) were performed within 6 weeks of MR imaging . The st and ard of reference was surgery with intraoperative ultrasonography ( US ) and biopsy and /or pathologic evaluation of resected liver segments and /or 3-month follow-up of nonresected segments if intraoperative US was not available . Three blinded review ers and unblinded site investigators identified liver lesions on segment maps . The Wilcoxon signed rank test was used to compare differences in per-patient sensitivity of precontrast and postcontrast MR images . Adverse events were recorded , and patient monitoring and laboratory assay were performed at time of injection and up to 24 hours after contrast material administration . RESULTS At MR imaging , 316 lesions were identified in 131 patients . In 77 % ( P = .012 ) , 72 % ( P = .15 ) , and 71 % ( P = .027 ) of patients for readers 1 , 2 , and 3 , respectively , more lesions were seen at precontrast and postcontrast MR imaging combined than at precontrast MR imaging alone . Sensitivity values for blinded readings were significantly greater at postcontrast MR imaging than at precontrast MR imaging for two of three blinded readers . For all blinded readers , combined precontrast and postcontrast MR images showed no difference in sensitivity compared with helical CT scans . The use of MR imaging , however , yielded fewer patients with at least one false-positive lesion ( 37 % , 31 % , and 34 % of patients for readers 1 , 2 , and 3 , respectively ) than did helical CT ( 45 % , 36 % , and 43 % of patients for readers 1 , 2 , and 3 , respectively ) . CONCLUSION Compared with precontrast MR imaging , postcontrast MR imaging with Gd-EOB-DTPA demonstrated improved sensitivity for lesion detection in the majority of blinded readers , with no substantial adverse events Aim : To evaluate diffusion-weighted MR imaging ( DWI ) , gadoxetic acid-enhanced MR imaging and the combination of both methods in the detection , classification , and characterization of focal liver lesions ( FLL ) . Methods : A total of 119 FLL ( 28 HCCs , 39 metastases , 15 FNHs , 11 adenomas , 13 hemangiomas , 13 cysts ) were retrospectively analyzed in 36 patients . In those patients MR imaging of the liver comprising respiratory-triggered DWI ( b values of 50 , 300 , and 600 s/mm2 ) and gadoxetic acid-enhanced MR imaging including image acquisition in the hepatocyte-selective phase ( 20 min post injection ) had been performed . Three image sets were assigned and compared : DWI only ( set A ) , gadoxetic acid-enhanced MR imaging only ( set B ) , and both modalities in combination ( set C ) . Two readers independently interpreted the images in r and om order . For each reader and image set , the area under the receiver operating characteristic curve ( Az ) and sensitivity in the detection of FLL was determined as well as the accuracy in the classification and characterization of FLL . Results : There was no significant difference between the three image sets in the detection of FLL with regards to Az . However , when only lesions with a diameter of 10 mm or less were analyzed , the Az values of set C were significantly higher than those of sets A and B for both readers . For classifying and characterizing FLL both set B and C were significantly superior to set A. Conclusion : Adding DWI to gadoxetic acid-enhanced MR imaging significantly increases the accuracy in the detection of small FLL Objectives : The aim of this prospect i ve study was to evaluate the diagnostic performance of magnetic resonance imaging ( MRI ) of the liver with the hepatocellular-specific contrast agent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid ( Gd-EOB-DTPA ) in comparison to precontrast MRI and spiral computed tomography ( CT ) in the specific diagnosis of focal nodular hyperplasia ( FNH ) and to describe morphologic features and enhancement pattern of FNH . Material s and Methods : In 176 patients from a phase III multicenter trial , 59 confirmed FNHs were present ( 13 = histopathology ; 46 = imaging follow-up within 12 months before or 3 months after the MRI study ) . MR examination consisted of precontrast T1- and T2-w sequences , T1-weighted ( w ) dynamic sequences after bolus-injection of 0.025 mmol Gd-EOB-DTPA ( Primovist ; Bayer Schering Pharma)/kg bodyweight and T1-w sequences with fat saturation in the hepatocyte-phase after 20 minutes . The number of correctly characterized FNHs was evaluated and compared with that determined on spiral CT in an on-site reading ( clinical study ) and an off-site reading ( 3 blinded readers ) . The morphologic appearance and enhancement patterns of the FNHs were evaluated . Results : Characterization with combined pre- and post-MRI ( 88.1 % ) was superior to that achieved with biphasic-enhanced spiral CT ( 84.7 % , not significant ) and precontrast MRI ( 67.8 % , P < 0.05 ) in the clinical study and significantly superior to both precontrast MRI and spiral CT for 2 of 3 blinded readers . Complete or partial enhancement of the lesions was present in the early dynamic phase ( arterial and portovenous dynamic phase ) in 94 % and 85 % , respectively . The pattern of lesion enhancement in the early dynamic phase was mainly homogenous ( 78%–80 % ) ; the median contrast-to-noise ratio was −5.9 in T1-w precontrast images , 14.0 in the arterial phase , 2.4 in the portovenous phase , and 2.9 in the equilibrium phase . Enhancement in the hepatocyte-phase after 10 and 20 minutes was observed in 88 % and 90 % of lesions , respectively . Conclusions : Characterization of FNH provided by Gd-EOB-DTPA-enhanced MRI is superior to that provided by precontrast MRI alone or spiral CT . FNHs show very similar enhancement characteristics to those of other extracellular contrast agents in the early dynamic phase after bolus injection of Gd-EOB-DTPA , after 20 minutes in the liver-specific phase enhancement is regularly seen PURPOSE To determine whether a multiphase method with high spatiotemporal resolution ( STR ) by means of a combination of parallel imaging , pseudor and om sampling and temporal view sharing improves the capture and intensity of gadoxetate arterial phase images as well as lesion enhancement . MATERIAL S AND METHODS Thirty-seven patients were imaged with a conventional spoiled gradient echo acquisition and 48 with a high STR multiphase acquisition after the administration of gadoxetate . Arterial phase capture , image quality , and quality of fat suppression were qualitatively grade d. Fourteen lesions in the conventional group and 28 in the high STR multiphase group were imaged , including 34 focal nodular hyperplasias . The ratio of lesion to parenchyma enhancement as well as relative hepatic artery enhancement were calculated . Chi-squared , Mann-Whitney U and student t-tests were used to compare differences . RESULTS The high STR multiphase acquisition included the arterial phase more frequently than conventional acquisitions ( P < 0.001 ) , with the arterial phase missed in 17 % ( 95 % CI of 4 - 28 % ) of patients with conventional acquisition compared with 2 % ( 95 % CI of 0 - 6 % ) with the high STR multiphase acquisition . There was no loss of image quality or degree of fat saturation . Additionally , there was increased relative intensity of the hepatic arteries ( P < 0.001 ) as well as lesion enhancement ( P = 0.01 ) . CONCLUSION The high STR multiphase acquisition result ed in more reliable gadoxetate arterial phase capture compared with a conventional acquisition while preserving image quality with robust fat saturation You are back where we put you in the previous article1 on diagnostic tests in this series on how to use the medical literature : in the library study ing an article that will guide you in interpreting ventilation-perfusion ( V/Q ) lung scans . Using the criteria in Table 1 , you have decided that the Prospect i ve Investigation of Pulmonary Diagnosis ( PIOPED ) study 2 will provide you with valid information . Just then , another OBJECTIVES The clinical management of hepatocellular adenoma ( HCA ) and focal nodular hyperplasia ( FNH ) is still subject to controversy , especially with respect to patient selection for surgery . The aim of this prospect i ve cohort study was to assess the outcomes of surgical intervention . METHODS Between January 2008 and September 2012 , patients diagnosed with FNH or HCA based on magnetic resonance imaging or computed tomography were enrolled in this prospect i ve study . Resection was undertaken in patients with HCA of > 5 cm or symptomatic lesions . Lesion characteristics , extent of liver resection ( minor : fewer than three segments ; major : three or more segments ) , morbidity ( by Dindo-Clavien class ) , mortality , postoperative length of stay and symptoms [ McGill Pain Question naire , including a visual analogue scale ( VAS ) ] were evaluated . RESULTS A total of 110 patients ( 106 female ; median age : 39 years ) were included ; 51 patients had HCA and 59 had FNH . Of the 110 patients , 49 underwent resection ( 33 HCA patients ; 16 FNH patients ) . Laparoscopic minor resection was performed in five HCA and five FNH patients ; open minor resection was performed in 19 HCA and seven FNH patients , and open major resection was performed in nine HCA and four FNH patients . Severe postoperative complications were observed in four patients ( Grade III , n = 3 ; Grade IV , n = 1 ) . Median baseline scores on the VAS were 6 in FNH patients and 7 in HCA patients ; the median VAS score after resection was 0 ( P = 0.008 ) . CONCLUSIONS If patients with HCA and FNH require surgery , limited resection can be carried out with low morbidity and without mortality . Patients with preoperative symptoms show a high rate of postoperative symptom relief |
2,328 | 22,695,275 | Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination .
Follow up in alternative setting s to the specialist clinic is acceptable to women but trials are underpowered for survival . | Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies .
This study aims to assess the evidence for benefits of follow-up in different setting s for women who have had treatment for early breast cancer . | Few r and omized controlled trials have examined the effects of combined aerobic and resistance training in breast cancer survivors soon after completing adjuvant therapy . Breast cancer survivors ( N = 58 ) within 2 years of completing adjuvant therapy were r and omly assigned to an immediate exercise group ( IEG ; n = 29 ) or a delayed exercise group ( DEG ; n = 29 ) . The IEG completed 12 weeks of supervised aerobic and resistance exercise , three times per week . The DEG completed the program during the next 12 weeks . Participants completed patient-rated outcomes at baseline , 6 , 12 , 18 and 24 weeks . The primary endpoint was overall quality of life ( QoL ) measured by the Functional Assessment of Cancer Therapy-Breast scale . Secondary endpoints were fatigue , social physique anxiety , and physical fitness . Follow-up data was obtained on 97 % of participants and exercise adherence was 61.3 % . Repeated measures analyses of variance revealed a significant group by time interaction for overall QoL ( P < 0.001 ) . Specifically , QoL increased in the IEG from baseline to 12 weeks by 20.8 points compared to a decrease in the DEG of 5.3 points ( mean group difference = 26.1 ; 95 % CI = 18.3–32.7 ; P < 0.001 ) . From 12 to 24 weeks , QoL increased in the DEG by 29.5 points compared to an increase of 6.5 points in the IEG ( mean group difference = 23.0 ; 95 % CI = 16.3–29.1 ; P < 0.001 ) . Similar results were obtained for the secondary endpoints . Combined aerobic and resistance exercise soon after the completion of breast cancer therapy produces large and rapid improvements in health-related outcomes BACKGROUND During the last decade , survival rates for breast cancer have increased as a result of earlier detection and increased use of adjuvant therapy . Limited data exist on the psychosocial aspects of the transitional period between the end of primary treatment and survivorship . We investigated the baseline psychosocial status of women enrolled in a r and omized trial testing two psychosocial interventions for women at the end of primary treatment . METHODS Participants , identified within 1 month after surgery ( registration ) , provided demographic information and limited measures of quality of life . They were followed until they finished primary treatment ( enrollment ) , at which time they completed a mailed baseline survey that included st and ardized measures of quality of life ( including st and ardized scales of physical and emotional functioning ) , mood , symptoms , and sexual functioning . A total of 558 patients ( mean age = 56.9 years ) were enrolled in the study between July 1 , 1999 , and June 30 , 2002 . Health outcomes were examined according to treatment received : mastectomy with and without chemotherapy , and lumpectomy with and without chemotherapy . All statistical tests were two-sided . RESULTS Among all treatment groups , patients who had a mastectomy had the poorest physical functioning at registration ( P<.001 ) and at enrollment ( P=.05 ) . At enrollment , mood and emotional functioning were similar among all patients , with no differences by type of treatment received . At enrollment , symptoms , including muscle stiffness , breast sensitivity , aches and pains , tendency to take naps , and difficulty concentrating , were common among patients in all groups and were statistically significantly associated with poor physical functioning and emotional well-being . Sexual functioning was worse for women who received chemotherapy than for those who did not , regardless of type of surgery ( P<.001 ) . CONCLUSIONS At the end of primary treatment for breast cancer , women in all treatment groups report good emotional functioning but report decreased physical functioning , particularly among women who have a mastectomy or receive chemotherapy . Clinical interventions to address common symptoms associated with treatment should be considered to improve physical and emotional functioning at the end of primary treatment for breast cancer The question of whether stress poses a risk for cancer progression has been difficult to answer . A r and omized clinical trial tested the hypothesis that cancer patients coping with their recent diagnosis but receiving a psychologic intervention would have improved survival compared with patients who were only assessed Background Current frequent follow-up after treatment for breast cancer does not meet its intended aims , but does depend on expensive and scarce specialized knowledge for routine history taking and physical examinations . The study described in this paper compared patient satisfaction with a reduced follow-up strategy , i.e. nurse-led telephone follow-up , to satisfaction with traditional hospital follow-up . Methods Patient satisfaction was assessed among patients ( n = 299 ) who were participants of a r and omized controlled trial investigating the cost-effectiveness of several follow-up strategies in the first year after treatment for breast cancer . Data on patient satisfaction were collected at baseline , three , six and 12 months after treatment , using the Dutch version of Ware 's Patient Satisfaction Question naire III ( PSQ III ) . In addition to general satisfaction , the PSQ III reports on satisfaction scores for technical competence , interpersonal aspects , and access of care . Regression analysis was used to predict satisfaction scores from whether or not nurse-led telephone follow-up was received . Results Nurse-led telephone follow-up had no statistically significant influence on general patient satisfaction ( p = 0.379 ) , satisfaction with technical competence ( p = 0.249 ) , and satisfaction with interpersonal aspects ( p = 0.662 ) . Regarding access of care , patient satisfaction scores were significantly higher for patients receiving telephone follow-up ( p = 0.015 ) . However , a mean difference at 12 months of 3.1 points was judged to be not clinical ly relevant . Conclusions No meaningful differences were found in satisfaction scores between nurse-led telephone and hospital follow-up in the first year after breast cancer treatment . With high satisfaction scores and the potential to substantially reduce clinic visits , nurse-led telephone follow-up may be an acceptable alternative to traditional hospital follow-up . Trial registration numberIS RCT N 74071417 Background After curative treatment for breast cancer women frequently attend scheduled follow-up examinations . Usually the follow-up is most frequent in the first 2–3 years ( 2–4 times a year ) ; thereafter the frequency is reduced to once a year in most countries . Its main aim is to detect local disease recurrence , or a second primary breast cancer , but also to provide information and psychosocial support . However , the cost-effectiveness of these frequent visits is under much debate , leading to a search for less intensive and more cost-effective follow-up strategies . In this paper the design of the MaCare trial is described . This trial compares the cost-effectiveness of four follow-up strategies for curatively treated breast cancer patients . We investigate the costs and effects of nurse-led telephone follow-up and a short educational group programme . Methods / design The MaCare trial is a multi centre r and omised clinical trial in which 320 breast cancer patients are r and omised into four follow-up strategies , focussed on the first 18 months after treatment : 1 ) st and ard follow-up ; 2 ) nurse-led telephone follow-up ; 3 ) arm 1 with the educational group programme ; 4 ) arm 2 with the educational group programme . Data is collected at baseline and 3 , 6 , 12 and 18 months after treatment . The primary endpoint of the trial is cancer-specific quality of life as measured by the global health/QoL scale of the EORTC QLQ-C30 . Secondary outcomes are perceived feelings of control , anxiety , patients ' satisfaction with follow-up and costs . A cost-effectiveness analysis will be performed from a societal perspective . Discussion Reduced follow-up strategies for breast cancer have not yet been widely applied in clinical practice . Improvement of psychosocial support and information to patients could lead to a better acceptance of reduced follow-up . The MaCare trial combines a reduced follow-up strategy with additional psychosocial support . Less frequent follow-up can reduce the burden on medical specialists and costs . The educational group programme can improve QoL of patients , but also less frequent follow-up can improve QoL by reducing the anxiety experienced for each follow-up visit . Results of the trial will provide knowledge on both costs and psychosocial aspects regarding follow-up and are expected in 2009 AIMS As a result of the rising prevalence of breast cancer and improved adjuvant treatment strategies , oncologists are faced with an ever-increasing workload of providing long-term follow-up care for early-stage breast cancer patients . In order to cope with these growing dem and s , innovative follow-up strategies are urgently required . MATERIAL S AND METHODS To explore if patient transfer back to the family physician for follow-up was a potential option , a prospect i ve programme of planned discharge was established for all patients who had completed adjuvant chemo/radiotherapy or had started adjuvant endocrine therapy . Patient and family physician information packages were also provided . RESULTS Between April and August 2005 , of the 193 patients assessed for transfer back to the family physician for follow-up care , transfer was possible in 43 % . Fifty-seven per cent ( or 110 patients ) were unsuitable for transfer back to the family physician . The reasons cited among those deemed unsuitable for transfer were as follows : clinical trial enrollment ( 50.9 % ) , ongoing endocrine treatment ( 31.8 % ) , new symptoms ( 6.3 % ) , and patient refusal ( 0.9 % ) . In both discharged and non-discharged groups , patients were also frequently being followed by other oncologists ( surgical and /or radiation ) . CONCLUSION Transfer of care back to family physicians for follow-up may offer a strategy to control workload volumes , and thus enable oncologists to focus their efforts on newly diagnosed and advanced-stage patients with more complex patient care needs BACKGROUND Routine follow-up of breast cancer patients in specialist clinics is st and ard practice in most countries . Follow-up involves regularly scheduled breast cancer check-ups during the disease-free period . The aims of follow-up are to detect breast cancer recurrence and to provide psychosocial support to the patient ; however , little is known about patients ' views on breast cancer follow-up . AIM To assess the effect on patient satisfaction of transferring primary responsibility for follow-up of women with breast cancer in remission from hospital outpatient clinics to general practice . METHOD R and omized controlled trial with 18 months ' follow-up in which women received routine follow-up either in hospital outpatient clinics or from their own general practitioner . Two hundred and ninety-six women with breast cancer in remission receiving regular follow-up care at two district general hospitals in Engl and were included in the study . Patient satisfaction was measured by means of a self-administered question naire supplied three times during the 18-month study period . RESULTS The general practice group selected responses indicating greater satisfaction than did the hospital group on virtually every question . Furthermore , in the general practice group there was a significant increase in satisfaction over baseline ; a similar significant increase in satisfaction over baseline was not found in the hospital group . CONCLUSION Patients with breast cancer were more satisfied with follow-up in general practice than in hospital outpatient departments . When discussing follow-up with breast cancer patients , they should be provided with complete and accurate information about the goals , expectations , and limitations of the follow-up programme so that they can make an informed choice PURPOSE To up date the 1999 American Society of Clinical Oncology ( ASCO ) guideline on breast cancer follow-up and management in the adjuvant setting . METHODS An ASCO Expert Panel review ed pertinent information from the literature through March 2006 . More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a r and omized design . RESULTS The evidence supports regular history , physical examination , and mammography as the cornerstone of appropriate breast cancer follow-up . All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination . Examinations should be performed every 3 to 6 months for the first 3 years , every 6 to 12 months for years 4 and 5 , and annually thereafter . For those who have undergone breast-conserving surgery , a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy . Thereafter , unless otherwise indicated , a yearly mammographic evaluation should be performed . Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling . The use of CBCs , chemistry panels , bone scans , chest radiographs , liver ultrasounds , computed tomography scans , [18F]fluorodeoxyglucose-positron emission tomography scanning , magnetic resonance imaging , or tumor markers ( carcinoembryonic antigen , CA 15 - 3 , and CA 27.29 ) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination . CONCLUSION Careful history taking , physical examination , and regular mammography are recommended for appropriate detection of breast cancer recurrence PURPOSE Women with breast cancer were provided with an audiotape of their primary adjuvant treatment consultation , and the following patient outcomes were measured at 12 weeks postconsultation : perceived degree of information provision , audiotape satisfaction and use , communication satisfaction with oncologist , mood state , and cancer-specific quality of life . PATIENTS AND METHODS Participants included 628 women newly diagnosed with breast cancer and 40 oncologists from six cancer centers in Canada . The patients were block r and omized to one of four consultation groups : st and ard care control , not audiotaped ; audiotaped , no audiotape given ; audiotaped , patient given audiotape ; and audiotaped , patient offered choice of receiving audiotape or not . RESULTS Patients receiving the consultation audiotape had significantly better recall of having discussed side effects of treatment than patients who did not receive the audiotape . Audiotape benefit was not significantly related to patient satisfaction with communication , mood state , or quality of life at 12 weeks postconsultation , and was not significantly affected by choice of receiving the audiotape . Patients rated the audiotape intervention positively , with an average score of 83.9 of 100 . CONCLUSION Audiotape provision benefits patients by facilitating their perception of being informed about treatment side effects , but does not significantly influence patient satisfaction with communication , mood state , or quality of life Objective To compare traditional hospital follow-up with telephone follow-up by specialist nurses after treatment for breast cancer . Design A two centre r and omised equivalence trial in which women remained in the study for a mean of 24 months . Setting Outpatient clinics in two NHS hospital trusts in the north west of Engl and Participants 374 women treated for breast cancer who were at low to moderate risk of recurrence . Interventions Participants were r and omised to traditional hospital follow-up ( consultation , clinical examination , and mammography as per hospital policy ) or telephone follow-up by specialist nurses ( consultation with structured intervention and mammography according to hospital policy ) . Main outcome measures Psychological morbidity ( state-trait anxiety inventory , general health question naire ( GHQ-12 ) ) , participants ’ needs for information , participants ’ satisfaction , clinical investigations ordered , and time to detection of recurrent disease . Results The 95 % confidence interval for difference in mean state-trait scores adjusted for treatment received ( −3.33 to 2.07 ) was within the predefined equivalence region ( −3.5 to 3.5 ) . The women in the telephone group were no more anxious as a result of foregoing clinic examinations and face-to-face consultations and reported higher levels of satisfaction than those attending hospital clinics ( intention to treat P<0.001 ) . The numbers of clinical investigations ordered did not differ between groups . Recurrences were few ( 4.5 % ) , with no differences between groups for time to detection ( median 60.5 ( range 37 - 131 ) days in hospital group v 39.0 ( 10 - 152 ) days in telephone group ; P=0.228 ) . Conclusions Telephone follow-up was well received by participants , with no physical or psychological disadvantage . It is suitable for women at low to moderate risk of recurrence and those with long travelling distances or mobility problems and decreases the burden on busy hospital clinics . Trial registration National Cancer Research Institute 1477 Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer , with six month follow-up . Design Pragmatic r and omised controlled prospect i ve open trial . Setting Three National Health Service oncology clinics in Scotl and and community exercise facilities . Participants 203 women entered the study ; 177 completed the six month follow-up . Interventions Supervised 12 week group exercise programme in addition to usual care , compared with usual care . Main outcome measures Functional assessment of cancer therapy ( FACT ) question naire , Beck depression inventory , positive and negative affect scale , body mass index , seven day recall of physical activity , 12 minute walk test , and assessment of shoulder mobility . Results Mixed effects models with adjustment for baseline values , study site , treatment at baseline , and age gave intervention effect estimates ( intervention minus control ) at 12 weeks of 129 ( 95 % confidence interval 83 to 176 ) for metres walked in 12 minutes , 182 ( 75 to 289 ) for minutes of moderate intensity activity reported in a week , 2.6 ( 1.6 to 3.7 ) for shoulder mobility , 2.5 ( 1.0 to 3.9 ) for breast cancer specific subscale of quality of life , and 4.0 ( 1.8 to 6.3 ) for positive mood . No significant effect was seen for general quality of life ( FACT-G ) , which was the primary outcome . At the six month follow-up , most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged . No adverse effects were noted . Conclusion Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later . Clinicians should encourage activity for their patients . Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services . Trial registration Current controlled trials IS RCT N12587864 OBJECTIVE To evaluate the effectiveness of early detection of intrathoracic and bone metastases in reducing mortality in breast cancer patients . DESIGN R and omized clinical trial allocating breast cancer patients to two alternative follow-up protocol s ( intensive vs clinical ) for at least 5 years . SETTING Twelve breast clinics ( referral centers ) in different areas in Italy . PATIENTS A total of 1243 consecutive patients ( either premenopausal or postmenopausal ) surgically treated for unilateral invasive breast carcinoma with no evidence of metastases . The two study groups were well balanced in terms of clinical and prognostic characteristics . INTERVENTION Patients in both treatment groups had physical examination and mammography , while patients of the intensive follow-up group had , in addition , chest roentgenography and bone scan every 6 months . MAIN OUTCOME MEASURES Vital status at 5 years was the main outcome ; information was available for all except five patients ( 0.4 % ) . Relapse-free survival was also analyzed . RESULTS Overall , 393 recurrences ( 104 local and 289 distant ) were observed during the study . Increased detection of isolated intrathoracic and bone metastases was evident in the intensive follow-up group compared with the clinical follow-up group ( 112 vs 71 cases ) , while no difference was observed for other sites and for local and /or regional recurrences . The 5-year relapse-free survival rate was significantly higher for the clinical follow-up group , with patients in the intensive follow-up group showing earlier detection of recurrences . No difference in 5-year overall mortality ( 18.6 % vs 19.5 % ) was observed between the two follow-up groups . CONCLUSIONS Periodic chest roentgenography and bone scan allow earlier detection of distant metastases , but anticipated diagnosis appears to be the only effect of intensive follow-up , and no impact on prognosis is evident after 5 years . Periodic intensive follow-up with chest roentgenography and bone scan should not be recommended as a routine policy Abstract Objective : To assess the effect on time to diagnosis of recurrence and on quality of life of transferring primary responsibility for follow up of women with breast cancer in remission from hospital to general practice . Design : R and omised controlled trial with 18 month follow up in which women received routine follow up either in hospital or in general practice . Subjects and setting : 296 women with breast cancer in remission receiving regular follow up care at district general hospitals in Engl and . Main outcome measures : Time between first presentation of symptoms to confirmation of recurrence ; quality of life measured by specific dimensions of the SF-36 schedule , the EORTC symptom scale , and hospital anxiety and depression scale . Results : Most recurrences ( 18/26 , 69 % ) presented as interval events , and almost half ( 7/16 , 44 % ) of the recurrences in the hospital group presented first to general practice . The median time to hospital confirmation of recurrence was 21 days in the hospital group ( range 1 - 376 days ) and 22 days in the general practice group ( range 4 - 64 ) . The differences between groups in the change in SF-36 mean scores from baseline were small : -1.8 ( 95 % confidence interval -7.2 to 3.5 ) for social functioning , 0.5 ( -4.1 to 5.1 ) for mental health , and 0.6 ( -3.6 to 4.8 ) for general health perception . The change from baseline in the mean depression score was higher in the general practice group at the mid-trial assessment ( difference 0.6 , 0.1 to 1.2 ) but there was no significant difference between groups in the anxiety score or the EORTC scales . Conclusion : General practice follow up of women with breast cancer in remission is not associated with increase in time to diagnosis , increase in anxiety , or deterioration in health related quality of life . Most recurrences are detected by women as interval events and present to the general practitioner , irrespective of continuing hospital follow up . Key messages Broadly , the goals of follow up are to detect recurrence , detect new contralateral primaries , and provide psychosocial support For women who are free of disease , general prac- tice follow up was not associated with increased time to diagnosis of recurrence or deterioration in health related quality of PURPOSE Breast cancer chemotherapy may cause unfavorable changes in physical functioning , body composition , psychosocial functioning , and quality of life ( QOL ) . We evaluated the relative merits of aerobic and resistance exercise in blunting these effects . PATIENTS AND METHODS We conducted a multicenter r and omized controlled trial in Canada between 2003 and 2005 that r and omly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care ( n = 82 ) , supervised resistance exercise ( n = 82 ) , or supervised aerobic exercise ( n = 78 ) for the duration of their chemotherapy ( median , 17 weeks ; 95 % CI , 9 to 24 weeks ) . Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale . Secondary end points were fatigue , psychosocial functioning , physical fitness , body composition , chemotherapy completion rate , and lymphedema . RESULTS The follow-up assessment rate for our primary end point was 92.1 % , and adherence to the supervised exercise was 70.2 % . Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem ( P = .015 ) , aerobic fitness ( P = .006 ) , and percent body fat ( adjusted P = .076 ) . Resistance exercise was superior to usual care for improving self-esteem ( P = .018 ) , muscular strength ( P < .001 ) , lean body mass ( P = .015 ) , and chemotherapy completion rate ( P = .033 ) . Changes in cancer-specific QOL , fatigue , depression , and anxiety favored the exercise groups but did not reach statistical significance . Exercise did not cause lymphedema or adverse events . CONCLUSION Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy , but they did improve self-esteem , physical fitness , body composition , and chemotherapy completion rate without causing lymphedema or significant adverse events BACKGROUND Menopausal symptoms ( e.g. , hot flashes , vaginal dryness , and stress urinary incontinence ) are very common in breast cancer survivors and can not be managed with st and ard estrogen replacement therapy ( ERT ) in these patients . The purpose of this study was to test the efficacy of a comprehensive menopausal assessment ( CMA ) intervention program in achieving relief of symptoms , the improvement in quality of life ( QOL ) , and sexual functioning in breast cancer survivors . METHODS Using a two-group , r and omized controlled design , we assigned 76 postmenopausal breast cancer survivors with at least one severe target symptom either to the intervention group or to a usual-care group . Seventy-two women were evaluable at the end of the study period . The CMA intervention , delivered by a nurse practitioner , focused on symptom assessment , education , counseling and , as appropriate , specific pharmacologic and behavioral interventions for each of the three target symptoms . Psychosocial symptoms were assessed with the use of a self-report screening instrument , and distressed women were referred for counseling if needed . The intervention took place over a 4-month period . Outcomes measured were scores on a composite menopausal symptom scale , the R AND Short Form Health Survey Vitality Scale , and the Cancer Rehabilitation Evaluation System ( CARES ) Sexual Functioning Scale at baseline and at 4-month follow-up . All statistical tests were two-sided and were performed at the alpha = . 05 significance level . RESULTS Patients receiving the intervention demonstrated statistically significant improvement ( P = .0004 ) in menopausal symptoms but no significant change in vitality ( P = .77 ) . Sexual functioning was statistically significantly improved ( P = .04 ) in the treatment group compared with the usual-care group . CONCLUSIONS A clinical assessment and intervention program for menopausal symptom management in breast cancer survivors is feasible and acceptable to patients , leading to reduction in symptoms and improvement in sexual functioning . Measurable improvement in a general QOL measure was not demonstrated Women with breast carcinoma commonly experience psychologic distress following their diagnosis . Women who participate in breast cancer support groups have reported significant reduction in their psychologic distress and pain and improvement in the quality of their lives . Web‐based breast cancer social support groups are widely used , but little is known of their effectiveness . Preliminary evidence suggests that women benefit from their participation in web‐based support groups The value of routine follow-up with frequent visits to a breast cancer specialist-both in terms of detection of recurrence and patient satisfaction-has been question ed . The aim of this study was to compare nurse-led follow-up on dem and versus physician follow-up after breast cancer treatment with regards to patients ' well-being , satisfaction , access to medical care and medical safety . Two hundred and sixty-four consecutively selected women with newly diagnosed breast cancer , classified as UICC stage I or stage II , were r and omised to follow-up at two hospitals in Sweden , either by routine medical follow-up , the physician group ( PG , n=131 ) , or on dem and by a specialist nurse , the nurse group ( NG , n=133 ) . Measures were done at baseline and twice a year over a period of 5 years by means of a question naire containing the Hospital Anxiety and Depression Scale ( HAD ) , and the Satisfaction and Accessibility ( SaaC ) scale . Number of contacts with the health care services , number of diagnostic procedures , and time to recurrence or death were monitored . The ratings of HAD and SaaC did not show any statistically significant differences between the groups . The levels of anxiety and depression were generally low and levels of patient satisfaction high . There were no differences between the groups concerning time to recurrence or death . This study indicates that women with breast cancer in stages I to II can be followed up by a specialist nurse with high patient satisfaction and good medical safety Introduction . Breast cancer follow-up programmes consume large re sources and despite the indications that several alternative approaches could be used effectively , there is no coherent discussion about costs and /or cost-effectiveness of follow-up programmes . Patient and methods . In a prospect i ve trial there were 264 breast cancer patients , stage I and II , r and omised to two different follow-up programmes- PG ( physician group ) and NG ( nurse group ) . The trial period was 5 years . The women in the two intervention groups did not differ in anxiety and depression , their satisfaction with care , their experienced accessibility to the medical centre or their medical outcome as measured by recurrence or death . The analyses were done from different lists representing costs at three hospitals in Sweden according to the principles of a cost minimization study . Results : The cost per person year of follow-up differed between the groups , with € 630 per person year in PG compared to € 495 per person year in NG . Thus , specialist nurse intervention with check-ups on dem and was 20 % less expensive than routine follow-up visits to the physician . The main difference in cost between the groups was explained by the numbers of visits to the physician in the respective study arms . There were 21 % more primary contacts in PG than NG . Discussion . The difference in cost per year and patient by study arm is modest , but transforms to nearly € 900 per patient and 5-year period , offering a substantial opportunity for reallocating re sources since breast cancer is the most prevalent tumour worldwide PURPOSE / OBJECTIVES To examine the effectiveness of a psychoeducational intervention on quality of life ( QOL ) in breast cancer survivors in post-treatment survivorship . DESIGN A r and omized controlled trial . SETTING An academic center collaborating with a regional cancer center in the southeastern United States . SAMPLE 256 breast cancer survivors . METHODS Women were r and omly assigned to the experimental or wait control group . The Breast Cancer Education Intervention ( BCEI ) study was delivered in three face-to-face sessions and five monthly follow-up sessions ( three by telephone and two in person ) . The control group received four monthly attention control telephone calls and the BCEI at month 6 . Data were collected at baseline , three and six months after the BCEI for the experimental group , and one month after the BCEI ( at month 7 ) for the wait control group . MAIN RESEARCH VARIABLES Primary endpoints were overall QOL and physical , psychological , social , and spiritual well-being . FINDINGS No differences in QOL were reported at baseline between groups . The experimental group reported improved QOL at three months , whereas the wait control group reported a significant decline in QOL . The experimental group reported continued maintenance of QOL at six months . Although the wait control group reported improved QOL at six months , significant differences continued to exist between the groups . CONCLUSIONS The BCEI was an effective intervention in improving QOL during the first year of breast cancer survivorship . Treatment effects were durable over time . IMPLICATION S FOR NURSING Post-treatment survivorship has not been empirically studied to a large degree . The BCEI is one of the few interventions demonstrating effectiveness among survivors after primary treatment , suggesting that oncology nurses may be uniquely positioned to provide safe passage using education and support AIM To examine a model of care for breast cancer patients based on the concept of point of need access and investigate the effectiveness of this model compared to routine 6-monthly clinical review s. DESIGN A parallel r and omised controlled trial was used to examine point of need access to specialist care via the nurse specialist , compared to routine hospital based 6-monthly clinical review at year two post breast cancer diagnosis . A total of 237 patients were recruited to the study . METHODS Outcome measures at baseline , 9 and 18 months included psychological morbidity using the GHQ12 question naire , quality of life using the FACT-B plus endocrine subscale , fear and isolation . An analysis of covariance was used to detect changes over time . Recurrences and methods of detection were recorded as secondary outcome measures . RESULTS Two hundred and fourteen patients completed the study . Overall patients were not exposed to risks of increased psychological morbidity ( p=0.767 ) or decline of quality of life ( p=0.282 ) when routine review was discontinued and no significant differences were detected during an 18-month period . Patients not receiving regular review did not feel isolated , and at the end of 18 months did not wish to return to 6-monthly clinical review s. The presentation of recurrences and short symptom history demonstrate that the recurrences observed were unlikely to have been detected at a routine visit . CONCLUSIONS Point of need access is acceptable to the majority of patients . Although a third of patients may wish to maintain a regular review , patient choice is important . Findings suggest that after 2 years following the diagnosis of breast cancer there is no evidence to support the view that regular clinical review improves psychological morbidity or quality of life . Patients do not appear to be compromised in terms of early detection of recurrence . Point of need access can be provided by suitably trained specialist nurses and provides a fast , responsive management system at a time when patients really need it BACKGROUND Results from r and omized trials indicate that treatment with tamoxifen or chemotherapy for primary breast cancer reduces the risk for contralateral breast cancer . However , less is known about how long the risk is reduced and the impact of factors such as age and menopausal status . METHODS The study included 634 women with contralateral breast cancer ( case patients ) and 1158 women with unilateral breast cancer ( control subjects ) from the Women 's Environment , Cancer and Radiation Epidemiology Study . The women were younger than age 55 when they were first diagnosed with breast cancer during 1985 - 1999 . Rate ratios ( RRs ) and 95 % confidence intervals ( CIs ) for contralateral breast cancer after treatment with chemotherapy or tamoxifen were assessed by multivariable adjusted conditional logistic regression analyses . RESULTS Chemotherapy was associated with a lower risk for contralateral breast cancer ( RR = 0.57 , 95 % CI = 0.42 to 0.75 ) than no chemotherapy . A statistically significant association between chemotherapy and reduced risk for contralateral breast cancer persisted up to 10 years after the first breast cancer diagnosis and was stronger among women who became postmenopausal within 1 year of the first breast cancer diagnosis ( RR = 0.28 , 95 % CI = 0.11 to 0.76 ) . Tamoxifen use was also associated with reduced risk for contralateral breast cancer ( RR = 0.66 , 95 % CI = 0.50 to 0.88 ) compared with no use , and the association was statistically significant for 5 years after the first diagnosis . CONCLUSION The associations between chemotherapy and tamoxifen treatment and reduced risk for contralateral breast cancer appear to continue for 10 and 5 years , respectively , after the initial breast cancer is diagnosed . Ovarian suppression may have a role in the association between chemotherapy and reduced risk for contralateral breast cancer This r and omized , controlled pilot trial was carried out to assess the feasibility and efficacy of an aerobic exercise in enhancing physical performance of breast cancer patients after adjuvant treatments . The potential of the training regimen to prevent accompanying bone loss was also assessed . Thirty patients , 41–65 years of age , were r and omly assigned into training or control groups shortly after adjuvant chemo- or radiotherapy . The 12-week training included a guided aerobic exercise session once a week ( the effective part being either step aerobic- or circuit-training in alternate weeks ) and similar home exercise sessions twice a week . Adherence to the guided sessions was 78 % , while home training was performed an average 2.1 times per week . Agility assessed with figure-8 running test and peak jumping power showed significant between-group treatment-effects ( ∼5 % and ∼10 % , respectively ) . Judged from the accelerometer data , reaction forces up to six times body weight occurred during the training , which implies that the training could also have potential to affect bone mass . The present exercise regimen turned out to be feasible and effective among breast cancer patients in terms of physical performance . Large controlled trials are necessary to confirm these findings The effectiveness of support group interventions for cancer patients has been established among White patients but has been virtually unstudied among minority patients . The current study represents the 1st r and omized support group intervention targeted to African American women with breast cancer . Participants ( N = 73 ) with nonmetastatic breast cancer were r and omly assigned to an 8-week group intervention or an assessment -only control condition At 12 months , the intervention result ed in improved mood as well as improved general and cancer-specific psychological functioning among women with greater baseline distress or lower income . Subsequent research is needed to address effective methods of enrolling and following women with fewer psychosocial and financial re sources , as they were the most likely to benefit from this particular intervention Abstract Objective : To compare the experiences of patients with breast cancer who were conventionally monitored with those in whom routine follow up was restricted to the time of mammography . Design : R and omisation to conventional schedule of clinic visits or to visits only after mammography . Both cohorts received identical mammography and were invited to telephone for immediate appointments if they detected symptoms . Setting : Combined breast clinic , Chelsea and Westminster Hospital . Subjects : 211 eligible out patients with a history of breast cancer . Main outcome measures : Acceptability of r and omisation , interim use of telephone and general practitioner , satisfaction with allocation to follow up . Results : Of 211 eligible patients , 196 ( 93 % ) opted for r and omisation in the study . Of these , 55 were under 50 years , 78 were diagnosed fewer than five years before , 90 had stage T2 - 4 tumours , and 71 had involved axillary nodes . Patients who did not participate were more likely to be under 50 years , to be two to five years after diagnosis , and to have had aggressive primary disease . Twice as many patients in both groups expressed a preference for reducing rather than increasing follow up . No increased use of local practitioner services or telephone triage was apparent in the cohort r and omised to less frequent follow up by specialists . Conclusions : Reducing the frequency of routine follow up has so far proved popular among patients with breast cancer at st and ard risk in this cohort . A multicentre study is needed to determine the effectiveness and cost-effectiveness of routine follow up with respect to disease outcomes . Key messages Although it is st and ard practice to advocate routine long term follow up of patients with breast cancer , the effectiveness of non-mammographic follow up has not been assessed in r and omised trials A key concern that has delayed the implementation of such trials is whether patients would find symptom driven follow up psychologically acceptable In this study most patients agreed to undergo r and omisation to less frequent follow up , though all continued with routine mammographic review After r and omisation more patients expressed a desire to reduce further , rather than increase , the frequency of follow up Patients undergoing less frequent review did not increase their use of general practitioner or telephone ( hotline ) As the prevalence of diagnosed breast cancer increases , it is important to define how best to provide long-term follow-up . Whereas many aspects of follow-up remain controversial , guidelines recommend surveillance mammograms as the only investigation to be performed routinely . We conducted a systematic review of the literature to eluci date the effect of routine surveillance mammograms on detecting ipsilateral recurrence ( IR ) and contralateral breast cancers ( CBC ) . The systematic review yielded 15 articles . All were observational studies and ranked as level II-2 or III evidence . There were no r and omized controlled trials identified . Most of the ten studies on detection of IR did not report on outcomes after detection . When reported , most studies found that the method of detection of IR did not influence overall survival or disease-free survival . Two of the nine studies on detection of CBC found that the CBC was detected at an earlier stage than the initial breast cancer , but did not report on long-term outcomes . This systematic review highlights the need for further research to help better define the optimum surveillance mammography regimen We present the results of a breast cancer clinical trial that tested two therapy interventions delivered by telephone . Women ( N = 218 ) with Stages I , II , or III breast cancer were r and omly assigned to breast cancer health education or emotional expression interventions , or to a st and ard care control condition . Outcome and process measures were obtained at baseline , 6-month and 13-month follow-ups . Oncology certified nurses conducted the therapies in six , 30-minute individual phone sessions . Women in the health education condition reported significantly better knowledge and less perceived stress compared to women in the emotional expression and control conditions . No treatment effects , however , were obtained for quality of life or mood , and all women generally improved on these measures over time . Secondary analyses showed that younger women and women with a more advanced stage of breast cancer reported significantly greater avoidant coping . The data show that telephone therapy is a viable delivery modality and that distress improves with time for most women . Overall , this study showed that neither of the two telephone interventions tested had a meaningful effect on quality of life or mood PURPOSE This study examines the impact of yoga , including physical poses , breathing , and meditation exercises , on quality of life ( QOL ) , fatigue , distressed mood , and spiritual well-being among a multiethnic sample of breast cancer patients . PATIENTS AND METHODS One hundred twenty-eight patients ( 42 % African American , 31 % Hispanic ) recruited from an urban cancer center were r and omly assigned ( 2:1 ratio ) to a 12-week yoga intervention ( n = 84 ) or a 12-week waitlist control group ( n = 44 ) . Changes in QOL ( eg , Functional Assessment of Cancer Therapy ) from before r and om assignment ( T1 ) to the 3-month follow-up ( T3 ) were examined ; predictors of adherence were also assessed . Nearly half of all patients were receiving medical treatment . RESULTS Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates ( P < .0001 ) . Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL ( P < .008 ) , emotional well-being ( P < .015 ) , social well-being ( P < .004 ) , spiritual well-being ( P < .009 ) , and distressed mood ( P < .031 ) . Sixty-nine percent of intervention participants attended classes ( mean number of classes attended by active class participants = 7.00 + /- 3.80 ) , with lower adherence associated with increased fatigue ( P < .001 ) , radiotherapy ( P < .0001 ) , younger age ( P < .008 ) , and no antiestrogen therapy ( P < .02 ) . CONCLUSION Despite limited adherence , this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors . Among patients not receiving chemotherapy , yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL This paper reports on a r and omised controlled trial assessing two types of outpatient follow up for women previously treated for stage 1 breast cancer now in remission . These were st and ard clinic follow up ( n = 31 , age range : 48 - 83 years ) and patient initiated follow up ( n = 30 , age range 53 - 87 years ) . The latter method involved giving the women written information on the signs and symptoms of recurrence and instructing them to telephone the Breast Care Nurse if they encountered any problems . The groups were compared in terms of cancer and breast cancer-specific quality of life , and psychological morbidity at recruitment , 6 months and 1 year . Satisfaction with follow up was assessed at 6 months and 1 year . Details regarding contact with healthcare professionals were collected at 1 year . There were no major differences in quality of life and psychological morbidity between the groups although more women in the st and ard clinic group reported reassurance and being checked as advantages whereas more women in the patient initiated follow up group reported convenience as an advantage . Patient initiated follow up is a potential alternative to st and ard clinic follow up for this group of women and appears to have no adverse effects . This could enable a cost saving to be made PURPOSE Most women with breast cancer are diagnosed at an early stage and more than 80 % will be long-term survivors . Routine follow-up marks the transition from intensive treatment to survivorship . It is usual practice for routine follow-up to take place in specialist clinics . This study tested the hypothesis that follow-up by the patient 's family physician is a safe and acceptable alternative to specialist follow-up . PATIENTS AND METHODS A multicenter , r and omized , controlled trial was conducted involving 968 patients with early-stage breast cancer who had completed adjuvant treatment , were disease free , and were between 9 and 15 months after diagnosis . Patients may have continued receiving adjuvant hormonal therapy . Patients were r and omly allocated to follow-up in the cancer center according to usual practice ( CC group ) or follow-up from their own family physician ( FP group ) . The primary outcome was the rate of recurrence-related serious clinical events ( SCEs ) . The secondary outcome was health-related quality of life ( HRQL ) . RESULTS In the FP group , there were 54 recurrences ( 11.2 % ) and 29 deaths ( 6.0 % ) . In the CC group , there were 64 recurrences ( 13.2 % ) and 30 deaths ( 6.2 % ) . In the FP group , 17 patients ( 3.5 % ) compared with 18 patients ( 3.7 % ) in the CC group experienced an SCE ( 0.19 % difference ; 95 % CI , -2.26 % to 2.65 % ) . No statistically significant differences ( P < .05 ) were detected between groups on any of the HRQL question naires . CONCLUSION Breast cancer patients can be offered follow-up by their family physician without concern that important recurrence-related SCEs will occur more frequently or that HRQL will be negatively affected PURPOSE The justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses ( IBTR ) outside the index quadrant are mostly new primary ( NP ) tumors that develop despite radiotherapy . We tested the hypothesis that whole-breast radiotherapy ( WBRT ) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT . METHODS AND MATERIAL S We retrospectively review ed 1,410 women with breast cancer who were entered into a prospect i ve r and omized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses ( IBTR ) and contralateral breast cancer ( CLBC ) . Cases of IBTR were classified into local recurrence ( LR ) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data . Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up . RESULTS At a median follow-up of 10.1 years , there were 150 documented cases of IBTR : 118 ( 79 % ) cases were definite or likely LR ; 27 ( 18 % ) cases were definite or likely NP ; and 5 ( 3 % ) cases could not be classified . There were 71 cases of CLBC . The crude proportion of definite-plus-likely NP was 1.9 % ( 27/1,410 ) patients compared with 5 % ( 71/1,410 ) CLBC patients . Cumulative incidence rates at 5 , 10 , and 15 years were 0.8 % , 2.0 % , and 3.5 % , respectively , for definite-plus-likely NP and 2.4 % , 5.8 % , and 7.9 % , respectively for CLBC , suggesting a difference in the rates of NP and CLBC . CONCLUSIONS This analysis suggests that WBRT reduces the rate of ipsilateral NP tumors . The late presentation of NP has implication s for the reporting of trials that are testing partial breast radiotherapy Given observational findings that physical activity reduces breast cancer risk , improves survival , and improves quality of life in breast cancer survivors , a need has been identified for r and omized controlled trials that testthe efficacy of exercise on biological mechanisms associated with breast cancer survival . The primary aims of the Yale Exercise and Survivorship Study were to 1 ) determine the feasibility of recruiting breast cancer survivors into a r and omized controlled trial of the effects of exercise on biological markers and /or mechanisms associated with survival , 2 ) compare the effectiveness of various recruitment strategies on accrual rates and baseline characteristics , and 3 ) report adherence to the exercise trial |
2,329 | 21,603,785 | CONCLUSION The effective presence of bias seriously weakened the reliability of the results from the dental studies evaluated , such that they would be of little use for clinicians and administrators as support for decision-making processes | CONTEXT AND OBJECTIVE Well-conducted r and omized controlled trials ( RCTs ) represent the highest level of evidence when the research question relates to the effect of therapeutic or preventive interventions .
However , the degree of control over bias between RCTs presents great variability between studies .
For this reason , with the increasing interest in and production of systematic review s and meta-analyses , it has been necessary to develop methodology supported by empirical evidence , so as to encourage and enhance the production of valid RCTs with low risk of bias .
The aim here was to conduct a method ological analysis within the field of dentistry , regarding the risk of bias in open-access RCTs available in the Lilacs ( Literatura Latino-Americana e do Caribe em Ciências da Saúde ) data base . | The effects of oral environment stabilization procedures on counts of C and ida spp . have rarely been discussed , and no conclusive results are found in the literature . The aim of this study was thus to ascertain the effects of oral environment stabilization procedures with glass ionomer and zinc oxide-eugenol cements on counts of C and ida spp . in the oral cavity of children . For this purpose , oral rinses of sterile phosphate-buffered saline were initially collected from 30 boys and 30 girls , positive for C and ida in the saliva and aged from 4 to 10 years . Data on the initial quantity of CFU/ml of C and ida were obtained . Then , the children were r and omly divided into two groups and oral environment stabilization procedures were performed using zinc oxide-eugenol cement or glass ionomer cement . One week after the procedures were performed , oral rinses were collected again and final C and ida counts were obtained . An expressive reduction in C and ida counts was observed in both groups . The zinc oxide-eugenol and glass ionomer cements were efficient in the reduction of C and ida counts and statistically significant differences were observed between initial and final counts in both groups . Considering the percentage of reduction , the zinc oxide-eugenol cement presented more favorable results , with a reduction of 70 % . A reduction of 46 % was observed with the use of the glass ionomer cement . According to the obtained results , we concluded that oral environment stabilization procedures were efficient in reducing C and ida spp . counts , especially when the zinc oxide-eugenol cement was employed OBJECTIVE The aim of this r and omized clinical trial was to evaluate the frequency of bacteriemia during endodontic treatment , with comparison between two techniques for biomechanical preparation of the root canal system . MATERIAL S AND METHODS The sample comprised 50 patients aged 16 to 52 years , of both genders , which were divided into 2 groups with 25 patients each . Group I underwent biomechanical preparation by the step-back technique , and Group II was treated by the rotary technique with nickel-titanium instruments ( K3 ) . Patients were su bmi tted to antisepsis of the oral cavity with chlorhexidine digluconate and three sample s of blood were collected for blood culture : preoperatively , immediately after the biomechanical preparation and 10 minutes later . The significance level adopted was 5.0 % , and analysis was performed by descriptive and inferential statistics by means of the Fisher 's exact test , Fisher-Freeman-Halton test and Student 's t test . Data were analyzed on the Statexact and SPSS softwares . RESULTS All blood cultures achieved before and immediately after preparation were negative . On the other h and , with regard to the blood cultures collected 10 minutes after preparation , one ( 4 % ) positive case was found for Group I. However , this difference was not statistically significant ( p = 0.50 ) . CONCLUSION The frequency of bacteriemia was low and observed just for Group Objective : The objective of this study was to evaluate the incidence of adverse effects reported by adolescents following 14 days of use of a mouthrinse containing 0.05 % NaF+0.12 % chlorhexidine . Methods : This double-blind study was developed as part of a r and omized clinical trial . The adolescents enrolled to the study were r and omly divided into two groups to use either : 0.05 % NaF+0.12 % chlorhexidine ( G1 , n=85 ) or 0.05 % NaF ( G2 , n=85 ) . Both groups used a 10mL solution of the mouthwash during 1 minute daily for 2 weeks under supervision . After that period , the subject 's acceptance of taste was measured using a verbal descriptive scale ( Labeled Magnitude Scale - LMS)11 . Participants were also interviewed regarding the occurrence of possible adverse effects during treatment ( temporary palate disorders , tooth staining or unpleasant taste ) . The proportional differences between the groups were tested using the chi-square test . Results : Palate changes were reported by 26 % of participants of each group ; 17.7 % of G1 and 32 % of G2 reported an unpleasant taste ( p = 0.062 ) , while staining was reported by 55 % of G1 and 68.9 % of G2 ( p = 0.117 ) . Absenteeism rates were similar in both groups ( G1= 2.58 ± 2.69 ; G2=2.81 ± 2.39 ) , p=0.362 . Conclusion : adherence was high in both groups and side effects reported by subjects were not perceived by them as being important . Since subjects ' acceptance and compliance is fundamental to the success of an oral health program , chlorhexidine-fluoride could be a useful re source in a program of plaque control Different dental procedures in children undergoing treatment can induce changes in blood pressure . These changes will be minimized if psychological treatment is applied prior to any procedure . The objective of this study was to determine changes in blood pressure ( systolic-diastolic ) in children undergoing psychological treatment before dental procedures . The population studied consisted of 100 children and adolescents , ages 6 to 15 years . The patients were assigned to two groups at r and om , i.e. with or without psychological treatment before dental procedures . Behavior management was carried out applying the tell-show-do technique of conduct h and ling . The systolic and diastolic blood pressures were measured prior to the initiation of the treatment , during drilling , restoring , and before dismissing the patient . The no-psychological treatment group exhibited significant differences in diastolic and systolic blood pressures during the dental procedure whereas the psychological treatment group evidence d no significant differences in blood pressure . No correlation was found between the alterations of blood pressure and the type of dental treatment performed . The application of the tell-show-do method would have an effect on the blood pressure in patients undergoing dental procedures Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available Chloral hydrate and hydroxyzine are a drug combination frequently used by practitioners to se date pediatric dental patients , but their effectiveness has not been compared to a negative control group in humans . The aim of this crossover , double-blinded study was to evaluate the effect of these drugs compared to a placebo , administered to young children for dental treatment . Thirty-five dental sedation sessions were carried out on 12 uncooperative ASA I children aged less than 5 years old . In each session patients were r and omly assigned to groups P ( placebo ) , CH ( chloral hydrate 75 mg/kg ) and CHH ( chloral hydrate 50 mg/kg plus hydroxyzine 2.0 mg/kg ) . Vital signs and behavioral variables were evaluated every 15 min . Comparisons were statistically analyzed using Friedman and Wilcoxon tests . P , CH and CHH had no differences concerning vital signs , except for breathing rate . All vital signs were in the normal range . CH and CHH promoted more sleep in the first 30 min of treatment . Overall behavior was better in CH and CHH than in P. CH , CHH and P were effective in 62.5 % , 61.5 % and 11.1 % of the cases , respectively . Chloral hydrate was safe and relatively effective , causing more satisfactory behavioral and physiological outcomes than a placebo The aim of this double-blind , controlled , split-mouth design ed clinical trial was to assess the effect of a single application of Gluma Desensitizer on alleviating dentin hypersensitivity . Twelve subjects entered the study and ten completed the protocol . Each subject had two teeth treated : one with Gluma Desensitizer according to the manufacturer 's instructions and one with water . The assessment of pain was performed with the VAS ( Visual Analogue Scale ) , after tactile ( probe ) , thermal ( cold blast of water ) and thermal/evaporative ( cold blast of air ) stimuli at baseline , immediately after treatment , after 1 week and after 4 weeks . The mean VAS values for the test and control teeth were compared by the paired t test ( alpha = 0.05 ) . Repeated measurements ANOVA was used to compare the different experimental times . The results showed that for test teeth , at baseline , mean VAS values were 1.76 ( + /- 2.82 ) , 7.10 ( + /- 2.10 ) and 4.75 ( + /- 2.65 ) , and , after 4 weeks , the mean values were 1.70 ( + /- 2.31 ) , 5.50 ( + /- 3.30 ) and 4.61 ( + /- 3.14 ) , respectively for probe , water and air stimuli . For the control teeth , at baseline , the mean VAS values were 1.86 ( + /- 2.92 ) , 6.61 ( + /- 2.31 ) and 4.08 ( + /- 2.91 ) and , after 4 weeks , 2.66 ( + /- 3.07 ) , 6.32 ( + /- 2.94 ) e 4.76 ( + /- 3.26 ) . There were no statistically significant differences between test and control teeth at any time . No intra-group differences were demonstrated either . It was concluded that Gluma Desensitizer had no effect on hypersensitive teeth from periodontally treated patients for a period up to 4 weeks The aim of this r and omised , double blind controlled trial was to verify the efficacy of a herbal dentifrice on the reduction of plaque and gingivitis . Forty eight volunteers with established gingivitis were r and omly assigned to either a test group ( herbal dentifrice ) or positive control group ( dentifrice with triclosan and fluoride ) . The dentifrices were distributed in plain white tubes by an independent pharmacy , which revealed the contents of each tube only after the experimental period . Plaque and gingivitis assessment s were carried out on baseline and after 28 days of product use . All examinations were conducted by the same calibrated investigator . Subjects were instructed to brush their teeth three times daily using their assigned dentifrice for 28 days . There was a significant reduction in plaque levels in both the test and control groups . However , there was no significant difference between the groups . A significant reduction in gingivitis was observed in both groups , although there was no significant difference between them . No adverse reactions were reported . The authors concluded that both dentifrices were effective in reducing plaque and gingivitis in subjects with established gingivitis The aim of the present study was to evaluate the efficacy of manual and electric toothbrushes in plaque control in periodontal patients after proper instructions . Thirty six periodontal patients ( mean age of 49 years , 21 females and 15 males ) were included and completed the study ( 100 % compliance ) . A single-blinded , r and omized , controlled , cross-over clinical design was adopted , with the patients using during 2 periods of 14 days each the manual and /or electric toothbrush . Four subgroups of 9 individuals were studied : A1 - -used manual toothbrush in both experimental periods ; A2 - -used the manual toothbrush during the first period and the electrical toothbrush during the second period ; B1 - -used electrical toothbrush during both periods ; B2 - -used the electrical toothbrush in the first period and the manual one in the second period . Brushing was performed during 14 days and at day 14 and 28 it was performed in the clinic , and timing of brushing was recorded without patients being aware . The Plaque Index ( Silness , Löe , 1964 ) was used . Intra-group comparisons were performed by paired t-test and inter-group comparisons by independent sample t-test , with an alpha level of 0.05 . The results showed no difference between the tested brushes neither for plaque nor for timing . However , re-instruction was detected as an important factor , since for all groups the second period , after reinstruction , showed lower plaque scores . It is concluded that professional advice and instruction and re-instruction seem more important in order to obtain good plaque control than the choice of toothbrush in subjects with periodontal disease UNLABELLED The dentin hypersensitivity is a painful condition rather prevalent in the general population . There are several ways of treatment for such condition , including the low intensity lasers . The proposal of this study was to verify the effectiveness of the Gallium-Aluminum-Arsenide diode laser in the treatment of this painful condition , using a placebo as control . MATERIAL S AND METHODS Thirty-two patients were selected , 22 females and 10 males , with ages ranging from 20 to 52 years old . The 32 patients were r and omly distributed into two groups , treated and control ; the sample consisted of 68 teeth , 35 in the treated group and 33 in the control group . The treated group was exposed to six laser applications with intervals from 48 to 72 hours , and the control group received , as placebo , applications of a curing light . RESULTS A significant reduction was observed in the pain condition between the initial phase and after six laser applications ; however , such reduction could also be observed for the control group exposed to the placebo . CONCLUSION Therapy with the low intensity Gallium-Aluminum-Arsenide laser - AsGaAl induces a statistically significant reduction in the painful condition after each application and between the beginning and end of treatment , although there was no statistically significant difference between the treated group ( laser ) and the control group ( placebo ) at the end of treatment and after the mediate evaluation results ( after 6 weeks ) , this way impairing the real measurement of laser effectiveness and placebo effect The aim of this prospect i ve study was to determine the effectiveness of caries preventive measures started during pregnancy on the caries experience of first-time mothers and their infants . Eighty-one pregnant women with low social background were selected on the basis of the presence of active carious lesions and were r and omly divided into control ( 38 ) and experimental ( 43 ) groups . The initial dental status ( DMFS and white spot lesions ) was established through clinical examination . The prophylactic measures were repeated during pregnancy and 6 and 12 months after delivery . Both groups received primary care intervention . They were instructed in relation to the etiologic factors of dental caries and received oral hygiene kits . Oral hygiene instructions were reinforced through interactive brushing . The experimental group also received antimicrobial treatment ( topical application of NaF and iodine solution immediately after prophylaxis and 3 and 5 days later ) and restorative care using glass ionomer cement . By the time the children were 2 years of age , 33.3 % of the infants in the control group and 14.7 % in the experimental group had caries activity . A significant difference in caries prevalence was observed between children with and without visible dental plaque . The mean number of tooth surfaces with carious lesions ( including areas of demineralization ) was higher among the children in the control group compared to the experimental group ( 6.3 x 3.2 ) , however , with no statistical significance . Maternal caries increase was a significant factor influencing the caries experience of the children . These data support the evidence of an association between caries prevalence in young children and clinical ( dental plaque ) and maternal factors Several different plant extracts have been evaluated with respect to their antimicrobial effects against oral pathogens and for reduction of gingivitis . Given that a large number of these substances have been associated with significant side effects that contraindicate their long-term use , new compounds need to be tested . The aim of this study was to assess the short-term safety and efficacy of a Lippia sidoides ( " alecrim pimenta")-based essential oil mouthrinse on gingival inflammation and bacterial plaque . Fifty-five patients were enrolled into a pilot , double-blinded , r and omized , parallel-armed study . Patients were r and omly assigned to undergo a 7-day treatment regimen with either the L. sidoides-based mouthrinse or 0.12 % chlorhexidine mouthrinse . The results demonstrated decreased plaque index , gingival index and gingival bleeding index scores at 7 days , as compared to baseline . There was no statistically significance difference ( p>0.05 ) between test and control groups for any of the clinical parameters assessed throughout the study . Adverse events were mild and transient . The findings of this study demonstrated that the L. sidoides-based mouthrinse was safe and efficacious in reducing bacterial plaque and gingival inflammation The purpose of this study was to evaluate cardiovascular parameters during dental procedures : systolic , diastolic , and mean blood pressures , and heart rate . Nineteen healthy normotensive patients ( 18 - 56 years of age ) received restorative treatment on three maxillary molars . The patients were continuously monitored by a non-invasive automatic monitor for blood pressure and heart rate during the pre- , trans- , and post-operative periods at the following stages : 15 min prior to anesthesia ; during topical anesthesia ; during infiltrative anesthesia ; for 5 minutes immediately after ; during cavity preparation ; during restorative procedure ; for 10 min after completion . Patients were divided into three groups : A ( without pre-medication ) , B ( preceded by 10 mg diazepam ) , and C ( preceded by placebo ) . All patients received infiltrative anesthesia containing 1.8 mL of 2 % lidocaine ( 36 mg ) with epinephrine 1:100,000 ( 18 microg ) . There were no changes in the parameters during the clinical procedures . When groups were compared , there were significant differences in diastolic arterial pressures during anesthesia Objectives : The antiplaque and antigingivitis effects of a gel containing 10 % Punica granatum Linn extract were evaluated using a 21-day partial-mouth experimental model of gingivitis . Methods : 23 volunteers participated in this cross-over , doubleblind study , carried out in 2 phases of 21 days each . For each period of the experiment , an acrylic toothshield was made for each volunteer to carry the test or placebo gel as well as to avoid brushing of the 4 experimental teeth ( posterior teeth in the lower left quadrant ) . The subjects were r and omly assigned to use either the placebo gel ( control group ) or the test gel ( experimental group ) and were instructed to brush the remaining teeth normally 3 times a day . On days 0 and 21 , the visible plaque index ( VPI ) and gingival bleeding index ( GBI ) were recorded . Results : The results did not show statistically significant difference between control and experimental groups for either of the indices ( VPI and GBI ) . Conclusion : The gel containing 10 % Punica granatum Linn extract was not efficient in preventing supragingival dental plaque formation and gingivitis OBJECTIVE The aim of the present study was to evaluate the efficacy of low-level laser therapy ( LLLT ) and the microelectric neurostimulation ( MENS ) in the treatment of patients with temporom and ibular disorders ( TMD ) . MATERIAL AND METHODS A sample of 19 individuals presenting with signs and symptoms of myogenic TMD was r and omly divided into two groups ( I - LLLT and II - MENS ) . Therapy was done in 10 sessions , three times a week , for one month . Patients were evaluated by the Visual Analogue Scale ( VAS ) , measurement of active range of motion ( AROM ) and muscle palpation , performed immediately before and 5 minutes after each therapeutic session by a blinded TMD specialist . The ANOVA for repeated measurements and Mann-Whitney tests were used for the statistical analysis . RESULTS The results showed an increase in maximum mouth opening and a decrease in tenderness to palpation for both groups . The VAS reduced for both groups , although more evident for the laser group ( p<0.05 ) . CONCLUSION Authors concluded that both therapies were effective as part of the TMD treatment , and the cumulative effect may have been responsible for this fact . However , caution is recommended when judging the results due to the self-limiting aspect of musculoskeletal conditions such as TMD Histories of clinical trials have recorded and analysed the development of quantification in therapeutic evaluation , the emergence of probabilistic thinking , the application of statistical methods and theory , and the sociology , ethics and politics of clinical trials ; but it is surprising that they only rarely identify as a distinct theme the development of efforts to control biases . An exception is Kaptchuk 's recent account of the history of blinding and placebos for reducing observer biases . In this complementary paper I introduce and discuss some milestones between 1662 and 1948 in the development of methods to control selection biases when assembling therapeutic comparison groups , to ensure , as far as possible , that ' like is compared with like ' . In the paper I note ( i ) that treatment allocation based on strict alternation abolishes selection bias as effectively as treatment allocation based on strict r and om allocation ; ( ii ) that use of schedules based on r and om numbers is more likely to prevent foreknowledge of allocation schedules , and thus the risk of introducing selection bias at the point of recruitment to trials ; ( iii ) that a concern to conceal allocation schedules was the rationale for using schedules based on r and om numbers in the Medical Research Council trials of vaccination for whooping cough and streptomycin for pulmonary tuberculosis ; and ( iv ) that the introduction of allocation concealment more than half a century ago remains the most recent substantive milestone in the history of efforts to control selection biases in therapeutic experiments We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 The aim of this study was to evaluate the efficacy of electro-acupuncture ( EAC ) on postoperative pain control after m and ibular third molar surgery . Twenty four young patients ( 12 male and 12 female ) with symmetrically impacted m and ibular third molars were selected . Each patient was su bmi tted to two separate surgical procedures under local anesthesia . At one side , extraction was carried out employing both prior ( 24h ) and immediately postoperative application of EAC , while on the contralateral side surgery was carried out without any treatment . EAC was applied on 6 bilateral systemic and 2 auricular points with a WQ10Dl appliance using 40 - 60Hz frequency for 20 min and individually adjusted intensity . Postoperative pain intensity was rated on a 100 mm visual analog scale ( VAS ) between 2 and 72 h and recording the amount of analgesics intake after surgery . Statistical analysis was performed using theWilcoxon test . Postoperative pain VAS scores were significantly lower for the EAC group ( p<0.05 ) and analgesic intake decreased ( p<0.05 ) for all evaluated periods ( p<0.05 ) . Under the tested conditions EAC therapy is efficient was proved controlling postoperative pain following m and ibular third molar surgical removal This study evaluated the fluoride intake from dentifrices with different fluoride concentrations ( [ F ] ) by children aged 24 - 36 months , as well as the influence of the dentifrice flavor in the amount of fluoride ingested during toothbrushing . Thirty-three children were r and omly divided into 3 groups , according to the [ F ] in the dentifrices : G-A ( 523 microgF/g ) , G-B ( 1,062 microgF/g ) and G-C ( 1,373 microgF/g ) . Dentifrices A and B are marketed for children , while dentifrice C is a regular product . The amount of F ingested was indirectly obtained , subtracting the amount expelled and the amount left on the toothbrush from the amount initially loaded onto the brush . The results were analyzed by ANOVA , Tukey 's test and linear regression analysis ( p < 0.05 ) . Children ingested around 60 % of the dentifrice loaded onto the brush , but no significant differences were seen among the groups ( p > 0.05 ) . Mean daily fluoride intake from dentifrice for G-A , G-B and G-C was 0.022(a ) feminine , 0.032(a ) feminine and 0.061(b ) mg F/kg body weight , respectively ( p < 0.01 ) . There was a strong positive correlation ( r = 0.86 , p < 0.0001 ) between the amount of dentifrice used and the amount of fluoride ingested during toothbrushing . The results indicate the need for instructing children 's parents and care givers to use a small amount of dentifrice ( < 0.3 g ) to avoid excessive ingestion of fluoride . The use of low-[F ] dentifrices by children younger than 6 years also seems to be a good alternative to minimize fluoride intake . Dentifrice flavor did not influence the percentage of fluoride intake The effectiveness of oral midazolam in pediatric dentistry is controversial . This r and omized , controlled , crossover , double blind clinical trial was conducted in order to study the effect of midazolam , used either alone or in association with hydroxyzine , during child dental treatment . Thirty seven dental sedation sessions were carried out on 11 ASA I uncooperative children less than five years-old . In each appointment children were r and omly assigned to groups : P - placebo , M - midazolam ( 1.0 mg/kg ) , or MH - midazolam ( 0.75 mg/kg ) plus hydroxyzine ( 2.0 mg/kg ) . Vital signs ( blood pressure , breathing rate , pulse and oxygen saturation ) and behavior parameters ( consciousness , crying , movement , overall behavior ) were evaluated every 15 minutes . Friedman and Wilcoxon statistical tests were used to compare groups and different moments in the same group . Normal values of vital signs were usually registered . Heart rate increased in groups P and M as the session went on . Group M presented less crying and movement at the first 15 minutes of treatment . Group MH caused more drowsiness at the beginning of the session . Overall behavior was better in group M than in groups P or MH . Group M produced effective sedation in 77 % of the cases , and group MH did so in 30.8 % . It was concluded that midazolam was effective and safe , and its association with hydroxyzine did not lead to additional advantages in pediatric dental sedation The aim of this r and omized , double-blind clinical trial was to evaluate the effect of the Paradontax dentifrice on the reduction of plaque and gingivitis . Subjects were r and omly allocated into either the test group ( n = 15 , Paradontax ) or the control group ( n = 15 , st and ard dentifrice with fluoride ) . Plaque levels were measured using the Turesky modification of the Quigley & Hein Plaque Index ( PI ) , and gingivitis was evaluated with the Gingival Index ( GI ) . Subjects were asked to brush their teeth with the allocated dentifrice , three times a day , for 21 days . There was no significant difference between groups in relation to the PI and GI medians , at baseline and at the end of the 21-day period . There was no significant reduction in PI in either the test or control groups . There was a significant decrease in GI in the test group . The authors concluded that there was no difference between the dentifrices in the reduction of plaque and gingivitis Low salivary flow rates are associated with higher oral C and ida spp . counts , which may predispose to oral c and idiasis . The aim of this study was to compare the effect of stimulating salivary flow rates with that of a regimen of chlorhexidine mouth rinse on the intensity of C and ida colonization in patients with reduced salivary flow rates . Thirty-one out patients were r and omized to stimulate salivary output ( group 1 ) or to receive chlorhexidine mouth rinses ( group 2 ) . Evaluations were performed at baseline ( T0 ) , at end of treatment ( T1 ) , and 15 days after last day of treatment ( T2 ) . Chewing-stimulated whole saliva sample s were collected at each visit . Group 1 showed a constant reduction in median cfu counts , although the difference was significant only between T0 and T2 ( p = 0.004 ) . Group 2 showed a reduction in median C and ida cfu counts between T0 and T1 ( p = 0.01 ) , but the counts increased at T2 ( p = 0.01 ) , and the difference between T0 and T2 was not significant ( p = 0.8 ) . In conclusion , patients who received salivary stimulation showed reductions of C and ida cfu counts in saliva and a trend for increasing salivary flow rates between baseline and end of study evaluations . The use of chlorhexidine mouth rinses dramatically reduced C and ida cfu counts , but when patients discontinued treatment , intensity of colonization rose again This study aim ed at evaluating the effectiveness of partial use of anterior repositioning appliances in the management of TMJ pain and dysfunction when compared to stabilization splints and a control group in a one-year follow-up . Sample was initially constituted by 60 patients , r and omly divided into three groups : I- stabilization splints , II- repositioning splints and III- no treatment . The whole sample was evaluated by means of TMJ and muscle palpation , m and ibular AROM , analysis of occlusal contacts , joint sounds inspection and Visual Analogue Scale ( VAS ) for one year ; 52 patients composed the final sample . A significant ( after 15 days ) improvement in pain report ( VAS ) and palpation index was found for group II ( p < or = 0.01 ) . The occurrence of occlusal alterations as posterior open bite or gross interferences after the splint therapy and increased muscle tenderness were not problems in this study . Similar results in joint noises reduction were observed for the entire sample . It was concluded that controlled partial use of repositioning splints is a beneficial tool in the management of intra-articular pain and dysfunction , with no risks of irreversible occlusal changes The aim of this study was to evaluate the VSC-inhibiting effect of a commercially available mouthrinse ( 0.1 % chlorine dioxide ) when compared to its placebo . A 2-step double blind , crossover , r and omised study was conducted with 14 dental students with healthy periodontium , who refrained from any mechanical plaque and tongue coating control during two 4-day experimental periods . The subjects were instructed to rinse 3 times daily with the assigned product during each period . A 7-day washout interval was established . VSCs levels were measured by a sulphide monitor at the beginning ( baseline ) and at the end of each experimental period . Statistical analyses were performed using Wilcoxon 's and Mann-Whitney 's non-parametric tests . At baseline , intragroup analysis revealed that VSCs levels did not differ between groups ( p > 0.05 ) ; at day 5 , the use of the chlorine dioxide mouthrinse did not change the baseline VSCs scores in the control group ( p > 0.05 ) , while a 2-fold increase was observed with the use of the placebo mouthrinse ( p < 0.05 ) . Intergroup analysis showed a significant difference between the VSCs levels of the test and control groups ( 40.2 + /- 30.72 and 82.3 + /- 75.63 ppb , p < 0.001 ) at day 5 . Within the limits of this study , the findings suggest that a mouthrinse containing chlorine dioxide can maintain VSCs at lower levels in the morning breath The aim of the present parallel , double-blind investigation was to evaluate the effect of using systemic metronidazole alone or associated to scaling and root planing on adult chronic periodontal disease , monitored at baseline , 30 , 60 and 90 days . Twelve subjects were divided into three groups : the first group ( Group I - 22 sites ) was su bmi tted to scaling and root planing ( SRP ) alone ; the second group ( Group II - 30 sites ) received SRP and 250 mg of metronidazole ( 3 times a day for 10 days ) , and the third group ( Group III - 31 sites ) was treated with metronidazole alone . The clinical parameters evaluated were probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PlI ) , gingival index ( GI ) and bleeding upon probing ( BP ) . Microbiological ( BANA test ) and enzymatic ( Pocket Watch ) tests were also performed . All three proposed treatments produced significant improvements in clinical conditions of subjects , from baseline , 30 , 60 and 90-day period , except for clinical attachment level . The results obtained by microbiological and enzymatic tests did not show statistical differences among the groups for the 90-day period ( r = 0.7924 and r = 0.7757 , respectively ) . In relation to clinical parameters , statistical differences among groups were observed only for the gingival index ( p = 0.0261 ) between Groups I and II , and probing depth ( p = 0.0124 ) between Group I and the others . We conclude that the use of systemic metronidazole did not produce additional effects on the microbiological conditions of these patients with chronic periodontal disease The objective of this split-mouth , double-blind , r and omized controlled trial was to compare the clinical effect of treatment of 2- or 3-wall intrabony defects with open flap debridement ( OFD ) combined or not with enamel matrix proteins ( EMP ) . Thirteen volunteers were selected with one pair of or more intrabony defects and probing pocket depth ( PPD ) > or = 5 mm . All individuals received instructions regarding oral hygiene and were su bmi tted to scaling and root planing . Each participant received the two treatment modalities : test sites were treated with OFD and EMP , and control sites received only OFD . After 6 months , a significant reduction was observed in PPD for the EMP group ( from 6.42 + /- 1.08 mm to 2.67 + /- 1.15 mm ) and for the OFD group ( from 6.08 + /- 1.00 mm to 2.00 + /- 0.95 mm ) ( p < 0.0001 ) , but with no significant difference between groups ( p = 0.13 ) . A significant gain in relative attachment level ( RAL ) was observed in both groups ( EMP : from 13.42 + /- 1.88 mm to 10.75 + /- 2.26 mm , p < 0.001 ; OFD : from 12.42 + /- 1.98 mm to 10.58 + /- 2.23 mm , p = 0.013 ) , but with no significant difference between groups ( p = 0.85 ) . Gingival recession ( GR ) was higher in the EMP group ( from 1.08 + /- 1.50 mm to 2.33 + /- 1.43 mm ; p = 0.0009 ) than in the OFD group ( from 0.66 + /- 1.15 mm to 1.16 + /- 1.33 mm ; p = 0.16 ) , but this difference was not significant ( p = 0.06 ) . In conclusion , the results showed that OFD combined with EMP was not able to improve treatment of intrabony defects compared to OFD alone A r and omized clinical trial was conducted to investigate the effect of a 0.5 % chlorhexidine ( CHX ) gel on dental plaque superinfecting microorganisms in mentally h and icapped patients . Thirty inmates from the institution " Casas And ré Luiz " were assigned to either test group ( CHX gel , n = 15 ) or control group ( placebo gel , n = 15 ) . The gel was administered over a period of 8 weeks . Supragingival plaque sample s were collected at baseline , after gel use ( 8 weeks ) and 16 weeks after baseline . The presence of Gram-negative Enterobacteriaceae , Staphylococcus and yeasts was evaluated . No significant growth of any superinfecting microorganism was observed in the CHX group , when compared to the placebo group . The results indicated that the 0.5 % chlorhexidine gel did not produce an undesirable shift in these bacterial population The aims of this double-blind r and omized clinical trial were to evaluate the presence of periodontal pathogens and the clinical response of periodontal pockets treatment to scaling and root planing ( SRP ) associated with subgingival minocycline ( SM ) . A total of 36 subjects , 26 to 60 years old ( 40.7 + /- 9.1 ) , who had been previously diagnosed with chronic periodontitis , were included in the present study . Eighteen subjects were selected for the test group ( TG ) , who were treated with SRP plus SM ( new treatment ) , and 18 subjects for the control group ( CG ) who received SRP plus vehicle ( current treatment ) . Two homologous sites in each subject with a probing depth ( PD ) > or = 6 mm were chosen . To evaluate the clinical response after treatment , PD was measured at baseline and at 90 days . Microbiological evaluation was performed to detect 7 periodontal pathogens using polymerase chain reaction at baseline , 30 , and 120 days . A mean reduction in PD of 2.8 and 2.1 mm was observed in the TG and CG , respectively . At baseline , P. gingivalis was the most prevalent organism in both test ( 65.8 % ) and control ( 48.6 % ) groups . After 120 days it fell to 30.8 % in TG and to 23.1 % in CG . There were no statistically significant differences between the test and control groups concerning PD ( p > 0.05 by Wilcoxon test ) or presence of periodontal pathogens ( p > 0.05 by Wilcoxon and chi-square ; p > 0.01 by Signal test ) . The results observed showed that the new treatment was as effective as the current treatment in reducing periodontal pathogens and PD among chronic periodontitis subjects The purpose of this study was to evaluate the effectiveness of subgingival application of Carisolv gel as an adjunctive therapy to scaling and root planing ( SRP ) on calculus removal compared to conventional instrumentation . Forty-five teeth requiring extraction due to severe periodontal disease were r and omized to the following treatments : 1 ) SRP alone ; 2 ) placebo gel + SRP ; 3 ) Carisolv gel + SRP . Either test or placebo gel was applied subgingivally for 1 min and then the root were instrumented until a smooth and calculus-free surface was achieved . Instrumentation time and the number of strokes required were recorded . After extraction , the efficacy of root surface instrumentation was measured by percentage of remaining calculus . There was no statistically significant difference ( p>0.05 ) between the treatment groups regarding either time required for instrumentation or the percentage of residual calculus . The subgingival application of Carisolv gel prior to SRP did not provide any additional benefit to root instrumentation compared to scaling and root planing alone OBJECTIVES To study publication trends , as well as the number and proportion of r and omised controlled trials covering different areas of periodontal research ( RCT -Ps ) . MATERIAL AND METHODS The study was based on Medline search es ( MeSH terms ) for the period 1980- 2000 . The RCT -Ps ( n = 675 ) were examined for relevance for different areas of periodontal research , journals of publication , and the countries of origin . RESULTS In periodontal research the annual number of publications had increased from 162 in 1980 to 440 in 2000 . Moreover , clinical trials in periodontal research ( CT-Ps ) had increased more than 10-fold , and RCT -Ps more than 15-fold . More than 4 out of 10 RCT -Ps covered the areas ' periodontal surgery ' and ' gingivitis and plaque treatment or prevention ' . More than 6 out of 10 RCT -Ps in total and more than 8 out of 10 RCT -Ps about ' periodontal surgery ' , were published in two different journals . U.S.A was the most common country of origin of RCT -Ps , contributing to almost 4 out of 10 RCT -Ps during 1988 - 2000 . CONCLUSION The annual number of RCT -Ps increased substantially during 1980 - 2000 , and a few clinical research areas predominated . Future research should give priority to areas where clinical evidence is scarce and where high- quality RCT -Ps are most needed This work evaluated the remineralization of demineralized enamel of pits and fissures of human third molars sealed with a glass ionomer cement ( Fuji IX , GC Corporation -- Japan ) or with a Bis-GMA sealant ( Delton -- Dentsply ) . Ten volunteers participated in this in situ study that consisted of two thirty-day periods using intra-oral devices , with a weeks interval in between . Four experimental treatment procedures and one control were r and omly assigned to the volunteers specimens : Group I , no treatment , control ; Group II , artificial caries process ; Group III , same treatment as Group II , but sealed with Delton ( Dentsply ) ; Group IV , same treatment as Group II , but sealed with Fuji IX ( GC Corporation -- Japan ) ; Group V , same treatment as Group II and no sealing . Groups I and II were not su bmi tted to the oral environment and served as controls . After a period of 30 days in the oral environment , the specimens were removed from the devices , embedded in acrylic resin , ground flat and polished . Then , Knoop hardness tests were performed , with a 25 g static load applied for 15 seconds . The measurements were made from the base of the fissure up to an opening of 600 microm , pre-established between the inclines of the cusps . Three indentations were then made , located at 25 , 75 , and 125 microm in depth from the outer enamel margin and 100 microm apart from each other ( Micromet 2003 ) . The Brieger F and Bonferronis tests were applied to the measurements . It was concluded that sealing with the glass ionomer cement Fuji IX was capable of making the enamel of pits and fissures more resistant by increasing the value of Knoop hardness STATEMENT OF PROBLEM R and omized controlled trials ( RCTs ) have become the gold st and ard for evaluating the effectiveness of treatment interventions . If not properly controlled , bias in the design of trial methodology can affect the validity of the study results . PURPOSE The purpose of this investigation was to assess the method ological quality of RCTs published in 3 prosthodontic journals over a 10-year period . MATERIAL AND METHODS Issues of The International Journal of Prosthodontics , The Journal of Prosthetic Dentistry , and The Journal of Prosthodontics published between 1988 and 1997 were search ed manually to identify RCTs . Specific inclusion and exclusion criteria were established to identify articles about studies that qualified as RCTs . Two independent review ers evaluated all qualified RCTs on the basis of how potential sources of bias in the trial methodology were controlled . Three areas -control of bias at entry , control of bias in assessment of outcome , and control of bias after entry-were evaluated with a scheme developed through the Cochrane Collaboration . A score of 1 or 0 was assigned for each of the 3 potential sources of bias , with the maximum quality score for an RCT being 3 ( good bias control ) and the minimum 0 ( poor control ) . Frequencies were calculated for each dimension of trial methodology and overall quality scores of the RCTs . RESULTS Sixty-two RCTs were identified from 3631 articles screened . The method of r and omization was explicit in only 47 % of the RCTs . Forty percent of RCTs incorporated blinding in the assessment of outcome , and 76 % accounted for all subjects at the end of the study . Overall quality scores revealed that only 16 % of RCTs attempted to control bias in all 3 areas examined . Forty percent were deficient in 1 area , 34 % were deficient in 2 areas , and 10 % were deficient in all areas examined . CONCLUSION The quality of RCTs published in prosthodontic journals may be improved by minimizing potential sources of bias and adequately reporting trial methodology |
2,330 | 23,572,464 | We could show a significant advantage of L-TERPT/TERPT over OPEN surgery regarding the incidence of soiling/incontinence and constipation .
No differences were seen for enterocolitis and anastomotic stricture .
We conclude from our data that L-TERPT/TERPT represents a valid option in the treatment of HD and might have some advantages over the OPEN techniques . | INTRODUCTION Various surgical techniques for the treatment of Hirschsprung disease ( HD ) have been proposed .
The most relevant long-term complications of HD surgery include constipation , soiling/incontinence , enterocolitis , and anastomotic stricture .
To date , there has been no r and omized controlled trial evaluating the long-term outcome of OPEN surgery compared with transanal approaches with and without laparoscopy ( laparoscopic-assisted transanal-endorectal pull-through [ L-TERPT ] and transanal-endorectal pull-through [ TERPT ] ) .
We performed a systematic literature review of the long-term outcome of OPEN surgery compared with L-TERPT/TERPT . | PURPOSE Transanal endorectal pull-through ( TEPT ) has drastically changed the treatment of Hirschsprung 's disease ( HD ) . A short follow-up of children su bmi tted to TEPT reveals results that are similar to the classic transabdominal pull-through procedures . However , few reports compare the late results of TEPT with transabdominal pull-through procedures with respect to complication rates and the fecal continence . The aims of the present work are to describe some technical refinements that we introduced in the procedure and to compare the short and long-term outcome of TEPT with the outcomes of a group of patients with HD who previously underwent the Duhamel procedure . METHODS Thirty-five patients who underwent TEPT were prospect ively studied and compared to a group of 29 patients who were treated with colostomy followed by a classical Duhamel pull-through . The main modifications introduced in the TEPT group were no preoperative colon preparation , operation conducted under general anesthesia in addition to regional sacral anesthesia , use of only one purse-string suture in the rectal mucosa before transanal submucosal dissection , and no use of retractors and electrocautery during the submucosal dissection . RESULTS The most frequent early complications of TEPT group were perineal dermatitis ( 22.8 % ) and anastomotic strictures ( 8.6 % ) . The comparison with patients who underwent Duhamel procedure revealed no difference in the incidence of preoperative enterocolitis , the patients of the TEPT group were younger at the time of diagnosis and of surgery , they had shorter operating times , and they began oral feeding more quickly after the operation . The incidence of wound infection was lower in the TEPT group . Moreover , the TEPT and Duhamel groups showed no difference in the incidences of mortality , postoperative partial continence , and total incontinence . Although the incidences of complete continence and postoperative enterocolitis were not different , a tendency to the increased incidence in the TEPT group was observed . CONCLUSIONS This study further supports the technical advantages , the simplicity , and the decreased incidence of complications of a primary TEPT procedure when compared to a classical form of pull-through . Some technical refinements are described , and no preoperative colon preparation was necessary for the patients studied here . The results show that the long-term outcomes of the modified TEPT procedure are generally better than those obtained with classical approaches Transanal one-stage endorectal pull-through ( TOSEPT ) has been presented as the most recent progression in treatment of Hirschsprung ’s disease ( HD ) , which may be able to replace various previous techniques . This prospect i ve study was design ed to compare the efficacy and probable complications of the commonly used open surgery with those of TOSEPT technique in management of HD . Forty-two children ( 35 boys and 7 girls ) between 3 days and 12 years of age underwent surgical treatment for HD — all after being diagnosed by barium enema over an 18-month period . In a manner of systematic r and om selection , 21 patients were operated by TOSEPT and the other 21 by Swenson procedures . All patients were followed-up at least for 12 months after hospital discharge . The necessary data containing age , sex , length of the resected aganglionic segment , intraoperative details , duration of hospital stay and postoperative functional results or complications were collected during hospitalization and follow-up period . There was no significant difference in age at the first operation , sex distribution and length of resected bowel between the two groups . Rate of postoperative complications were significantly higher in Swenson procedure group ( P < 0.01 ) . Narcotics were needed in all patients of Swenson procedure group but only in two patients operated by TOSEPT also required laparotomy ( P < 0.001 ) . The hospitalization period of TOSEPT group was also less than that of Swenson group ( P < 0.001 ) . The total cost of treatment by Swenson procedure is considerably higher than by TOSEPT . TOSEPT can significantly diminish postoperative pain , surgical complications , hospital stay and cost burden caused by Hirschsprung ’s disease . Besides , this procedure is cosmetically preferable because no visible scar remains AIM Our aim was to examine the long-term bowel dysfunction that followed surgery for Hirschsprung 's disease . METHODS Of 414 patients diagnosed with Hirschsprung 's disease between 1974 and 2002 , 98 were interviewed using a structured question naire to provide an assessment of bowel function , medication , diet , physical and social limitations . Forty-two completed a prospect i ve 4-week toileting diary and 16 underwent anorectal manometry . RESULTS Four of the 98 patients had permanent stomas and 10 had Down 's syndrome . Of the remaining 84 patients ( mean age 12 + /- 8 years , range 1.9 - 41.9 years ) , 13 % ( 11/84 ) had heavy soiling by day and 17 % ( 14/84 ) by night . Fifty percent reported episodic urgency , but 36 % also reported episodic constipation . Stool consistency was looser in patients with a history of long segment disease . Some aspects of bowel function improved with age . Enuresis was much more frequent than expected . Sixty-four percent reported adverse reactions to foods , particularly to fruit , vegetables , fats and diary products , and 15 % limited their social activities because of fecal incontinence . There were no significant differences in manometric parameters between those patients who soiled and those who did not . CONCLUSIONS Fecal incontinence is common after surgery for Hirschsprung 's disease and has a significant impact on social activities . Some aspects of bowel function did improve with age . Adverse reactions to food were unexpectedly frequent and need to be further studied PURPOSE The reported incidence of Hirschsprung's-associated enterocolitis ( HAEC ) is extremely variable . A st and ardized definition would permit comparison of different studies and provide an interpretable outcome measure for future prospect i ve studies in patients with Hirschsprung 's disease . METHODS The Delphi method is a technique for achieving consensus among a panel of experts . A list of 38 potential criteria from the history , physical examination , radiologic studies , and pathologic specimens was made available to pediatric surgeons and gastroenterologists who have contributed to the literature on Hirschsprung 's disease . Each expert ranked the diagnostic importance of each item using a Likert scale . In subsequent surveys , the same process was used , but the means and SDs from previous rounds were included as a way of influencing the experts toward consensus . Cronbach 's alpha was used after each round to measure variability among the experts . Once consensus was reached , an overall " HAEC score " was developed by assigning a value of 1 or 2 to each item that was considered important by the expert panel . The score was then vali date d by circulating 10 clinical cases to the panel and asking if each represented HAEC or not . RESULTS Twenty-seven experts completed the survey . Cronbach 's alpha increased from 0.93 after the first round to 0.97 after the second . Criteria receiving the highest scores were diarrhea , explosive stools , abdominal distension , and radiologic evidence of bowel obstruction or mucosal edema . Eighteen items were included in the score . During the validation process , the score agreed with the experts in 9 of the 10 case scenarios . CONCLUSION The most important clinical diagnostic criteria for HAEC were identified from a larger pool of potential diagnostic items through a consensus approach using the Delphi method . A score was developed and vali date d and can now be used as a st and ardized and reproducible outcome measure for future studies in children with Hirschsprung 's disease PURPOSE A new endorectal pull-through technique using a transanal approach is presented in this report . METHODS Mucosectomy , colectomy , and pull-through are performed transanally , and neither laparotomy or laparoscopy are required . Five patients affected with Hirschsprung 's disease have been operated on with this technique . CONCLUSION During the 6- to 15-month follow-up period , all of them have had postoperative normal bowel movements AIM To evaluate the indications , results , and complications of Transanal Endorectal Pull-Through ( TEPT ) in the management of rectosigmoid Hirschsprung 's disease ( HD ) compared with the open technique . PATIENTS AND METHODS Between November 1998 and March 2002 , 68 Transanal Endorectal Pull-Through ( TEPT ) procedures were performed in infants and children . The patients ' ages ranged from 6 days to 13 years . The primary diagnosis in all 68 patients was Hirschsprung 's disease confined to the rectosigmoid region . All children were operated without construction of a pre-operative colostomy except for one patient . Follow-up period ranged from 6 - 46 months ( mean 32 months ) . These patients were compared with fifty patients who had undergone open pull-through for HD during the period from November 1995 to October 1998 . RESULTS AND COMPLICATIONS For the TEPT group , the mean operating time was 90 min and the average length of resected bowel was 25 cm . Sixty-two patients had satisfactory results without complications . Blood transfusion was needed in eleven patients only . Recovery was very fast and patients were often hungry within 24 hours . Feeding was resumed within 48 hours . One patient required laparotomy during the procedure due to injury to the urethra . Two patients required colostomy 3 and 5 days after surgery because of delayed leakage . Three patients suffered from attacks of enterocolitis 6 - 9 months postoperatively . There was increased frequency of defecation ( 5 - 15 times daily ) for 4 - 6 weeks after surgery in all patients . There was no constipation , no incontinence , no cuff abscess and no mortality in any of the patients . Average frequency of defecation was 1 - 3 times daily after 3 months postoperatively . For the open technique group , mean operating time was 150 min , the length of the average resected segment was 29 cm . Forty-one patients had satisfactory results without complications . The cost of the open technique was almost double that of the TEPT ( 6300 vs. 3200 pounds ) . CONCLUSIONS Transanal Endorectal Pull-Through ( TEPT ) is characterized by a shorter operating time , less bleeding , shorter hospital stay , less morbidity and earlier recovery than similar open pull-through procedures . The hazards and morbidities associated with laparotomy and colostomy may be avoided with a one-stage technique in Hirschsprung 's disease confined to the rectosigmoid area ( 70 - 80 % ) . Careful long-term follow-up is required to assess continence and sexual function BACKGROUND The transanal one-stage endorectal pull-through operation for Hirschsprung 's disease is relatively new and makes assessment of the functional outcome and colonic motility difficult . The aim of this study was to evaluate the stooling patterns and colonic motility after a one-stage transanal pull-through operation for Hirschsprung 's disease in children . METHODS Twenty-two children who underwent a one-stage transanal pull-through operation for Hirschsprung 's disease were followed up for at least 6 months . The children ( 17 boys and 5 girls ) were from 12 months to 13 years of age ( mean age , 4 years ) . All patients had an aganglionic segment confined to the rectosigmoid area ( confirmed by preoperative barium enema and postoperative histology ) . Clinical outcome was assessed by interviews and question naires , and children were divided into symptomatic and nonsymptomatic groups . Contrast barium enema and defecography and determination of total and segmental colonic transit time ( using radio-opaque markers ) were performed on all 22 children . RESULTS The stooling patterns were considered satisfactory in 17 children . Of all the children , the mean stool times were 1 to 2 per day and only 2 were 8 to 10 per day ; postoperative soiling was found in 4 , constipation was observed in 2 , and Hirschsprung-associated enterocolitis in 1 . There was no incontinence , cuff infection , anastomotic leak , or mortality noted . Barium enema showed that the dilated and spastic colonic segment disappeared in all 22 children . The dilated sigmoid loops decreased in 17 ( 2 symptomatic , 15 nonsymptomatic ) and disappeared in 5 ( 4 symptomatic , 1 nonsymptomatic ) . There was a significant difference between the decreasing and disappearing loop group in regard to stooling disorders ( P < .05 ) . Postoperative defecography showed that the anorectal angle of all children was open , fixed , and significantly larger than that of the preoperative and control groups ( 123.3 degrees + /- 15.1 degrees vs 84.7 degrees + /- 8.3 degrees vs 79.0 degrees + /- 11.6 degrees , P < .01 ) and larger in the symptomatic group when compared with the nonsymptomatic group ( 135.6 degrees + /- 15.9 degrees vs 111.0 degrees + /- 14.3 degrees , P < .05 ) . Postoperatively , the total gastrointestinal transit time , left colonic transit time , and rectosigmoid colonic transit time of all the children were shorter than preoperatively ( 26.8 + /- 8.2 vs > 188 hours , P < .01 ; 6.3 + /- 4.1 vs > 60 hours , P < .01 ; 11.8 + /- 4.4 vs > 120 hours , P < .01 ) and similar to controls . The total gastrointestinal transit time and rectosigmoid colonic transit time of the symptomatic group were significantly shorter than the nonsymptomatic group ( 25.2 + /- 5.6 vs 28.1 + /- 10.1 hours , P < .05 ; 12.2 + /- 6.7 vs 9.8 + /- 4.0 hours , P < .05 ) . CONCLUSIONS The stooling pattern and colonic motility are satisfactory in most children after the one-stage transanal pull-through operation for Hirschsprung 's disease . Normalization of colon appearance and total and segmental colonic transit time are signs of recovery of colonic motility . Stooling disorders were noted in a few cases and may be related to decrease or disappearance of the sigmoid loop , dysfunction of the " neorectosigmoid " , an open and fixed anorectal angle , and ischemia of the pull-through segment BACKGROUND / PURPOSE Transanal endorectal pull-through ( TEPT ) is the latest development in treatment of Hirschsprung 's disease ( HD ) . This prospect i ve study was design ed to evaluate the safety and efficacy of 1 stage TEPT technique in the management of patients with HD . METHODS One hundred forty-nine children ( 116 boys and 33 girls ) aged 8 days to 14 years underwent 1 stage TEPT procedure over an 18-month period at 5 Egyptian academic pediatric surgical centers and affiliated hospitals . Median follow-up was 12 months ( range , 3 to 21 months ) . These patients were evaluated with regard to age , sex , length of the aganglionic segment , intraoperative details , and postoperative functional results or complications . An electromyogram ( EMG ) , endorectal ultrasound scan , and lower gastrointestinal ( GI ) motility studies were reserved for patients with postoperative problems with bowel control . RESULTS Mean operating time was 120.2 + /- 27.8 minutes ( range , 60 to 210 minutes ) . The average length of resected bowel was 26.8 + /- 12.4 cm ( range , 15 to 45 cm ) . Thirteen patients required laparotomy because of extension of aganglionic segment beyond the sigmoid colon in 9 , tear in the mesenteric vessels in 2 , and difficulties in getting to the submucosal plane in 2 . Three deaths ( 2 % ) occurred 3 days , 4 days , and 4 weeks postoperatively , respectively . Postoperative complications included transient perianal excoriation in 48 patients ( 30 were <3 months of age ) , enterocolitis ( n = 26 ) , anastomotic stricture ( n = 7 ) , recurrent constipation ( n = 6 ) , hypoganglionosis at distal end of pulled through segment ( n = 2 ) , cuff abscess ( n = 3 ) , anastomotic leak ( n = 1 ) , adhesive bowel obstruction ( n = 1 ) , and rectal prolapse ( n = 1 ) . Complete anorectal continence was noted in 35 of 42 ( 83.3 % ) children older than 3 years , whereas soiling and frequent accidents still occur in 7 , who showed a steady improvement in their continence status . CONCLUSIONS One-stage TEPT technique is both feasible and safe technique in properly selected children with rectosigmoid HD in all ages . The technique is easily learned and is associated with excellent clinical results BACKGROUND It has been hypothesized that the extensive transanal dissection in transanal endorectal pull-through ( TEPT ) for Hirschsprung disease ( HD ) can impair the anal sphincters in neonates and thereby cause incontinence . Theoretically , transabdominal endorectal pull-through might have less impact on the sphincters . The aim of this study was to compare functional outcome in HD patients operated with either TEPT or laparotomy-assisted endorectal pull-through ( LEPT ) with particular focus on soiling and fecal incontinence . PATIENTS AND METHODS Anorectal function in 52 children older than 3 years is reported . The patients were operated for HD with either TEPT ( n = 28 ) or LEPT ( n = 24 ) and followed prospect ively . Functional outcome was recorded by st and ardized interviews . The Krickenbeck criteria were used to classify voluntary bowel movements , soiling , and constipation . RESULTS The median age at follow-up was 5.7 years ( 3.1 - 13.2 ) for TEPT and 10.1 years ( 7.7 - 16.2 ) for LEPT . Twenty-nine patients reported soiling at final follow-up . There was no difference in the rate of soiling between children operated with TEPT ( 54 % ) or LEPT ( 58 % ) . Constipation was reported in 11 children ( TEPT , 25 % ; LEPT , 17 % ) . CONCLUSIONS The functional outcome and in particular the rate of soiling did not differ between patients operated with LEPT or TEPT INTRODUCTION Endorectal pull-through ( ERPT ) is a widely accepted procedure for the treatment of Hirschsprung 's disease ( HSCR ) . This study was aim ed at presenting the long-term results of patients with classic HSCR who were operated on with a laparoscopic-assisted Georgeson procedure and to compare them to patients treated with a Soave-Boley procedure . PATIENTS AND METHODS Patients treated for Hirschsprung disease in the period 1997 - 2006 with a minimum follow-up of 6 months were prospect ively included in this study . Demographic details , associated anomalies , surgical technique , length of aganglionosis , and postoperative complications were collected . A question naire was su bmi tted to all families to assess general health , bowel adaptation , fecal and urinary continence , cosmetic results , and patients ' and parents ' perspective of overall outcome . RESULTS Overall , 162 patients underwent a pull-through procedure : 25 patients treated with Georgeson and 21 with Soave-Boley ERPT were eligible for this study . Conversion was required in 3 of 28 patients approached laparoscopically . Hospitalization was shorter for patients treated laparoscopically ( P < 0.05 ) , whereas length of surgery was comparable . Complication rate was similar for both groups , as well as growth that remained within normal ranges for age . Long-term outcome , in terms of bowel movements , was similar . None of the patients experienced fecal and /or urinary incontinence . Cosmetic results proved to be excellent to good in all patients undergoing the Georgeson and in 67 % of patients undergoing the Soave-Boley procedure ( P < 0.05 ) . Patients ' perspective of overall outcome was excellent in more than 90 % of patients from both groups . CONCLUSIONS Overall results proved to be similar . Likewise , long-term bowel function did not show significant differences . Nonetheless , if we consider hospitalization and cosmetic results , it becomes clear that the minimally invasive approach should be preferred , when possible , to improve patients ' comfort , perspective of overall health status , and psychologic acceptance |
2,331 | 19,420,093 | Data for serum copper suggested its value as a biomarker , reflecting changes in status in both depleted and replete individuals , although these changes were smaller in the latter .
Total ceruloplasmin protein is related to copper status but reflects changes in highly depleted individuals only .
Erythrocyte superoxide dismutase and urinary deoxypyridinoline are not useful biomarkers , but there were insufficient data to draw firm conclusions about plasma , erythrocyte , and platelet copper ; leukocyte superoxide dismutase ; erythrocyte , platelet , and plasma glutathione peroxidase ; platelet and leukocyte cytochrome-c oxidase ; total glutathione ; diamine oxidase ; and urinary pyridinoline .
Despite limited data , serum copper appears to be a useful biomarker of copper status at the population level . | BACKGROUND The assessment of dietary adequacy of copper is constrained by the absence of recognized copper status biomarkers .
OBJECTIVES The objectives were to systematic ally review the usefulness of copper status biomarkers and identify those that reflected changes in status over > or = 4 wk . | The study of Cu metabolism is hampered by a lack of sensitive and specific biomarkers of status and suitable isotopic labels , but limited information suggests that Cu homeostasis is maintained through changes in absorption and endogenous loss . The aim of the present study was to employ stable-isotope techniques to measure Cu absorption and endogenous losses in adult men adapted to low , moderate and high Cu-supplemented diets . Twelve healthy men , aged 20 - 59 years , were given diets containing 0.7 , 1.6 and 6.0 mg Cu/d for 8 weeks , with at least 4 weeks intervening washout periods . After 6 weeks adaptation , apparent and true absorption of Cu were determined by measuring luminal loss and endogenous excretion of Cu following oral administration of 3 mg highly enriched (65)Cu stable-isotope label . Apparent and true absorption ( 41 and 48 % respectively ) on the low-Cu diet were not significantly different from the high-Cu diet ( 45 and 48 % respectively ) . Endogenous losses were significantly reduced on the low- ( 0.45 mg/d ; P<0.001 ) and medium- ( 0.81 mg/d ; P=0.001 ) compared with the high-Cu diet ( 2.46 mg/d ) . No biochemical changes result ing from the dietary intervention were observed . Cu homeostasis was maintained over a wide range of intake and more rapidly at the lower intake , mainly through changes in endogenous excretion A double-blind study was done giving 10 mg of copper/day as copper gluconate or placebo capsules for 12 wk . The seven subjects receiving copper gluconate had no change in the level of copper in the serum , urine , or hair . There was also no change in the levels of zinc or magnesium . There was also no significant change in levels of hematocrit , triglyceride , SGOT , GGT , LDH , cholesterol , or alkaline phosphatase . The side effects of nausea , diarrhea , and heartburn were the same in the subjects receiving copper gluconate and subjects receiving placebo capsules We examined the effects of low-copper diets on indexes of immune response of 11 healthy men ( aged 21 - 32 y ) during a 90-d metabolic suite study . Daily copper intake for the first 24 d , next 42 d , and the last 24 d of the study was 0.66 , 0.38 , and 2.49 mg , respectively . Feeding the diet with 0.38 mg Cu/d was associated with a significant ( P < or = 0.05 ) decrease in the proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin , Concanavalin A , or pokeweed , and an increase in the percentage of circulating B cells ( CD 19 + ) , but had no effect on the concentration of serum interleukin 2 receptor , the percentage of peripheral monocytes , neutrophils , CD3 + , CD4 + , or CD8 + T cells ; or on the neutrophil phagocytic activity . Feeding 2.49 mg Cu/d for 24 d prevented further decreases in the indexes affected by the low-copper diet but did not restore them to the pre study concentrations , even though plasma copper and ceruloplasmin concentrations were restored to normal The effects of calcium supplementation ( as calcium citrate malate , 1000 mg elemental Ca/d ) with and without the addition of zinc ( 15.0 mg/d ) , manganese ( 5.0 mg/d ) and copper ( 2.5 mg/d ) on spinal bone loss ( L2-L4 vertebrae ) was evaluated in healthy older postmenopausal women ( n = 59 , mean age 66 y ) in a 2-y , double-blind , placebo-controlled trial . Changes ( mean + /- SEM ) in bone density were -3.53 + /- 1.24 % ( placebo ) , -1.89 + /- 1.40 % ( trace minerals only ) , -1.25 + /- 1.46 % ( calcium only ) and 1.48 + /- 1.40 % ( calcium plus trace minerals ) . Bone loss relative to base-line value was significant ( P = 0.0061 ) in the placebo group but not in the groups receiving trace minerals alone , calcium alone , or calcium plus trace minerals . The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals ( P = 0.0099 ) . These data suggest that bone loss in calcium-supplemented , older postmenopausal women can be further arrested by concomitant increases in trace mineral intake A study was conducted in young men to evaluate the effect of a low-copper diet on copper absorption , excretion , and retention . Eleven young men were confined to a metabolic research unit for 90 d. The study was divided into three periods , with dietary copper as the only variable . Dietary copper intake was 0.66 mg/d for 24 d , 0.38 mg/d for 42 d , and 2.49 mg/d for 24 d. The stable isotope 65Cu was fed to five of the subjects once during the first and last dietary period and twice , early and late , in the second period to determine copper absorption . 65Cu was infused into an arm vein of the other six subjects once during each dietary period to estimate excretion of endogenous copper . Total copper and 65Cu were determined by isotope dilution with thermal-ionization mass spectrometry . Fractional absorption was significantly higher during the low-copper period than in either period with higher dietary copper and excretion of the infused isotope was significantly lower in the low-copper period . Subjects were in negative balance early in the first two periods but achieved balance by the end of those periods . They retained copper during the highest dietary copper period ( third period ) . The results suggest that endogenous copper excretion is a major point of regulation of the body 's copper stores . Regulation of absorption and of endogenous excretion in response to dietary copper intake helps to protect against deficiency and toxicity . However , this regulation was not sufficient to maintain copper status at the lowest intake of dietary copper , 0.38 mg/d Red cell superoxide dismutase ( SOD ) activity was evaluated as a biochemical index of copper nutrition in a double-blind study of 17 infants recovering from malnutrition and receiving marginal copper intakes . Children were paired on admission by sex , birth weight , nutritional status and antecedents of diarrhea and breast feeding . Nine served as controls receiving a copper sulfate supplement ( 80 micrograms/kg daily for 120 d ; eight received a placebo and were supplemented only if plasma copper levels dropped below 90 micrograms/dl or on d 90 for at least 30 d. After copper supplementation there was a significant rise ( paired t-test ; P less than 0.05 ) in plasma copper ( 96 vs. 165 micrograms/dl ) ; ceruloplasmin ( 33 vs. 50 mg/dl ) and SOD ( 1073 vs. 1371 U/g Hb ) . After supplementation these values were similar to those of the controls . SOD was correlated with plasma copper ( r = 0.78 ; P less than 0.001 ) and not with weight-for-age or weight-for-length . Addition of copper in vitro did not modify the SOD activity . Red cell SOD is a good marker of copper nutrition in humans and correlates well with plasma copper BACKGROUND Numerous studies have examined the effect of low and adequate intakes of copper on absorption and retention , but little information is available on the regulation of absorption and retention of copper when intake is high . OBJECTIVE A study was conducted in men to determine the effect of long-term high copper intake on copper absorption , retention , and homeostasis . DESIGN Nine men were confined to a metabolic research unit ( MRU ) for 18 d and were fed a 3-d rotating menu containing an average of 1.6 mg Cu/d . They continued the study under free-living conditions for 129 d , supplementing their usual diets with 7 mg Cu/d . They then returned to the MRU for 18 d and consumed the same diet as during the first period , except that copper intake was 7.8 mg/d . The stable isotope (63)Cu was fed to 3 subjects and infused into the other 6 on day 7 of each MRU period , and complete urine and stool collection s were made throughout the study . Total copper and (63)Cu were determined by inductively coupled plasma mass spectrometry . Copper absorption , excretion , and retention were calculated on the basis of dietary , urinary , and fecal copper and (63)Cu . RESULTS Results were as follows when comparing the high copper intake with the usual intake : fractional copper absorption was significantly lower , but the amount absorbed was significantly higher ; excretion of the infused (63)Cu was significantly faster ; and total retention was significantly higher . CONCLUSIONS Homeostatic regulation of copper absorption and retention helped to minimize the amount of copper retained with high copper intake but was not sufficient to prevent retention of > 0.6 mg Cu/d Western diets containing suboptimal Cu concentrations could be widespread . A link between marginal Cu deficiency and CVD has been suggested . The objective of the present study was to investigate the effect of Cu supplementation on both Cu status and CVD risk factors in healthy young women . Sixteen women with a mean age of 24 ( sd 2 ) years participated in a r and omised crossover study of three 4-week periods with 3-week washouts between periods . During each intervention period , subjects received 0 , 3 or 6 mg elemental Cu/d as CuSO4 in addition to their habitual diet . Blood sample s were taken to assess the effect of supplementation on putative markers of Cu status . The content of plasma lipids , lipoprotein ( a ) , apo and certain haemostatic factors , as putative indices of CVD , was also analysed . Daily supplementation with 3 mg Cu significantly increased ( P < 0.05 ) serum Cu concentration and the activity of erythrocyte superoxide dismutase , although there was no further significant increase after an intake of 6 mg Cu/d . The concentration of the fibrinolytic factor plasminogen activator inhibitor type 1 was significantly reduced ( P < 0.05 ) by about 30 % after supplementation with 6 mg Cu/d . No other marker of Cu status or CVD risk factor was affected by Cu supplementation . The results indicate that supplementation with 3 or 6 mg Cu/d may improve Cu status in these healthy young women . Increased Cu intake could reduce the risk of CVD and atherosclerosis in man by promoting improved fibrinolytic capacity In rats , copper deficiency leads to low copper metalloenzyme activity , high serum cholesterol , and cardiovascular lesions . In humans , moderately low copper intake may be common , but the consequences remain largely uncertain . The present study examined the effects of copper supplementation ( 2 mg/d for 4 weeks in a copper/placebo crossover design ) in 20 adult men with moderately high plasma cholesterol . End-point measurements were three copper enzyme activities , erythrocyte superoxide dismutase ( SOD ) , plasma ceruloplasmin ( Cp ) , and plasma diamine oxidase ( DAO ) , and three parameters related to the risk of cardiovascular disease ( CVD ) , plasma cholesterol , plasma lipoprotein ( a ) [ Lp(a ) ] , and lag times for very-low-density lipoprotein ( VLDL ) and low-density lipoprotein ( LDL ) oxidation in vitro . Although copper had no significant effects on any parameter for the entire study group , it did significantly increase two enzyme activities ( SOD and DAO ) , as well as lipoprotein oxidation lag times , in 10 subjects in the lower half of a median split for precopper values . Thus , copper supplementation appeared to influence some types of measurements in subjects beginning with less than median values No sensitive functional index is currently available to assess Cu status in healthy human population s. This study evaluated the effect of Cu supplementation on putative indices of Cu status in twelve women and twelve men , aged between 22 and 45 years , who participated in a double-blind placebo controlled crossover study . The study consisted of three 6-week supplementation regimens of 3 mg CuSO4 , 3 mg Cu-glycine chelate and 6 mg Cu-glycine chelate , each separated by placebo periods of equal length . Women had significantly higher caeruloplasmin oxidase activity ( P < 0.001 ) , caeruloplasmin protein concentration ( P < 0.05 ) , and serum diamine oxidase activity ( P < 0.01 ) at baseline than men . Erythrocyte and leucocyte superoxide dismutase activity , leucocyte cytochrome c oxidase activity , and erythrocyte glutathione peroxidase activity did not respond to Cu supplementation . Platelet cytochrome c oxidase activity was significantly higher ( P < 0.01 ) , after supplementation with 6 mg Cu-glycine chelate in the total group and in women but did not change in men . Caeruloplasmin oxidase activity was significantly higher ( P < 0.05 ) , in men after supplementation with 3 mg Cu-glycine chelate , while caeruloplasmin protein concentration was significantly lower in men after supplementation with 6 mg Cu-glycine chelate ( P < 0.05 ) . Serum diamine oxidase activity was significantly higher after all supplementation regimens in the total group and in both men and women ( P < 0.01 ) . These results indicate that serum diamine oxidase activity is sensitive to changes in dietary Cu intakes and may also have the potential to evaluate changes in Cu status in healthy adult human subjects A multicenter European study ( FoodCue ) was undertaken to provide data on the significance of increased dietary copper as a pro-oxidant or antioxidant in vivo . The present work describes the effect of Cu supplementation on ( 2,2'-azo-bis(2-amidinopropane ) hydrochloride (AAPH)-induced red blood cell oxidation in middle-aged people . Double-blinded copper supplementation was achieved in 26 healthy volunteers ( 50 - 70 years ) with pills containing 3 mg CuSO(4 ) , 3 mg Cu glycine chelate ( CuG ) and 6 mg CuG. Each 6 week supplementation period was preceded and followed by 6 weeks of washout ( WO ) on placebo . The results show significant increases in time necessary to achieve 50 % hemolysis ( LT(50 ) ) after 3CuSO(4 ) and 6CuG compared with values after WO periods . Cu supplementation did not increase the levels of (Cu , Zn)SOD activity in red blood cells . Resistance to hemolysis was significantly and positively correlated ( r = .30 , p < .01 ) with alpha- and beta-carotene content in the plasma . Together , these data suggest that intake of copper as high as 7 mg/d has no pro-oxidant activity and may rather result in protection of red blood cells against oxidation . The decreased oxidizability of red blood cells did not result from increased (Cu , Zn)SOD activity and may occur through other mechanisms such as changes in membrane antioxidant content The oxidative modification of low-density lipoprotein cholesterol ( LDL ) has been implicated in the pathogenesis of atherosclerosis . Copper ( Cu ) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation . Nevertheless , Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro . Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant , a multicenter European study ( FOODCUE ) was instigated to provide data on the biological effects of increased dietary Cu . Four centers , Northern Irel and ( coordinator ) , Engl and , Denmark , and France , using different experimental protocol s , examined the effect of Cu supplementation ( 3 or 6 mg/d ) on top of normal Cu dietary intakes or Cu-controlled diets ( 0.7/1.6/6.0 mg/d ) , on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers . Each center coordinated its own supplementation regimen and all sample s were subsequently transported to Northern Irel and where lipid peroxidation analysis was completed . The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation . These data show that high intakes ( up to 6 mg Cu ) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation Background / Aims : Copper is routinely used in the laboratory to promote oxidation in vitro . However , copper concentrations are million-fold higher than physiological concentrations and , in contrast , accumulating evidence suggests that copper may have an antioxidant role in vivo . The aim of this study was to provide data on how increased intake of copper affected mononuclear leukocyte DNA damage and liver function in healthy young free-living men and women . Methods : The study design was a double-blind repeated crossover trial with treatment and intervening placebo periods , each of 6 weeks ’ duration . The following supplementations were given orally in sequence : CuSO4 at a dose of 3 mg copper/day and copper amino acid chelates at doses of 3 and 6 mg copper/day . Oxidative DNA damage was assessed using a modification of the alkaline Comet assay incorporating an endonuclease III digestion step . The assessment of liver function was by measurement of the liver enzymes , alanine aminotransferase and L-γ-glutamyltransferase . Results : There was no significant alteration in mononuclear leukocyte DNA damage or on liver function after 6 weeks of copper supplementation at two doses ( 3 and 6 mg/day ) . Conclusions : Copper supplementation ( giving total copper intake at the highest level of 7 mg/day ) did not induce DNA damage or adversely affect liver function in healthy adults |
2,332 | 22,876,779 | Conclusion : In acute medically ill patients , prolonged thromboprophylaxis with an oral FXa inhibitor is more protective than regular short-term treatment with enoxaparin .
However , treatment with FXa inhibitors is significantly associated with major bleeding , both in long- and short-term treatment compared with enoxaparin | Abstract Introduction : Venous thromboembolism ( VTE ) is a common and potentially avoidable cause of morbidity and mortality in patients hospitalized for acute medical illness .
Objective : Our objective was to conduct a systematic review of studies that assessed the efficacy and safety of new oral anticoagulant ( OAC ) drugs versus st and ard pharmacological drugs and /or placebo in prevention of VTE in acute medically ill patients . | BACKGROUND Extended- duration low-molecular-weight heparin has been shown to prevent venous thromboembolism ( VTE ) in high-risk surgical patients . OBJECTIVE To evaluate the efficacy and safety of extended- duration enoxaparin thromboprophylaxis in acutely ill medical patients . DESIGN R and omized , parallel , placebo-controlled trial . R and omization was computer-generated . Allocation was central ized . Patients , caregivers , and outcome assessors were blinded to group assignment . ( Clinical Trials.gov registration number : NCT00077753 ) SETTING : 370 sites in 20 countries across North and South America , Europe , and Asia . PATIENTS Acutely ill medical patients 40 years or older with recently reduced mobility ( bed rest or sedentary without [ level 1 ] or with [ level 2 ] bathroom privileges ) . Eligibility criteria for patients with level 2 immobility were amended to include only those who had additional VTE risk factors ( age > 75 years , history of VTE , or active or previous cancer ) after interim analyses suggested lower-than-expected VTE rates . INTERVENTION Enoxaparin , 40 mg/d subcutaneously ( 2975 patients ) , or placebo ( 2988 patients ) , for 28 + /- 4 days after receiving open-label enoxaparin for an initial 10 + /- 4 days . MEASUREMENTS Incidence of VTE up to day 28 and of major bleeding events up to 48 hours after the last study treatment dose . RESULTS Extended- duration enoxaparin reduced VTE incidence compared with placebo ( 2.5 % vs. 4 % ; absolute risk difference favoring enoxaparin , -1.53 % [ 95.8 % CI , -2.54 % to -0.52 % ] ) . Enoxaparin increased major bleeding events ( 0.8 % vs. 0.3 % ; absolute risk difference favoring placebo , 0.51 % [ 95 % CI , 0.12 % to 0.89 % ] ) . The benefits of extended- duration enoxaparin seemed to be restricted to women , patients older than 75 years , and those with level 1 immobility . LIMITATION Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial . CONCLUSION Use of extended- duration enoxaparin reduces VTE more than it increases major bleeding events in acutely ill medical patients with level 1 immobility , those older than 75 years , and women . PRIMARY FUNDING SOURCE Sanofi-aventis Betrixaban is an oral direct inhibitor of factor Xa ( FXa ) being developed for the prevention of venous thromboembolism ( VTE ) . Its antithrombotic effects had not been previously tested in patients . This exploratory clinical trial in the US and Canada r and omized 215 patients undergoing elective total knee replacement ( TKR ) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o . bid or enoxaparin 30 mg s.c . q12h , respectively , for 10 - 14 days . The betrixaban dosage was blinded , but enoxaparin was not . Primary efficacy outcome was the incidence of VTE , consisting of deep-vein thrombosis ( DVT ) on m and atory unilateral ( operated leg ) venography , symptomatic proximal DVT , or pulmonary embolism ( PE ) through Day 10 - 14 . Safety outcomes included major and clinical ly significant non-major bleeds through 48 h after treatment . All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee . Of 214 treated patients , 175 ( 82 % ) were evaluable for primary efficacy . VTE incidence was 14/70 ( 20 % ; 95 % CI : 11 , 31 ) for betrixaban 15 mg , 10/65 ( 15 % ; 95 % CI : 8 , 27 ) for betrixaban 40 mg , and 4/40 ( 10 % ; 95 % CI : 3 , 24 ) for enoxaparin . No bleeds were reported for betrixaban 15 mg , 2 ( 2.4 % ) clinical ly significant non-major bleeds with betrixaban 40 mg , and one ( 2.3 % ) major and two ( 4.6 % ) clinical ly significant non-major bleeds with enoxaparin . A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed . Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied BACKGROUND The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain . We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin . METHODS In this double-blind , double-dummy , placebo-controlled trial , we r and omly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban , administered orally at a dose of 2.5 mg twice daily for 30 days , or enoxaparin , administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days . The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism , pulmonary embolism , symptomatic deep-vein thrombosis , or asymptomatic proximal-leg deep-vein thrombosis , as detected with the use of systematic bilateral compression ultrasonography on day 30 . The primary safety outcome was bleeding . All efficacy and safety outcomes were independently adjudicated . RESULTS A total of 6528 subjects underwent r and omization , 4495 of whom could be evaluated for the primary efficacy outcome --2211 in the apixaban group and 2284 in the enoxaparin group . Among the patients who could be evaluated , 2.71 % in the apixaban group ( 60 patients ) and 3.06 % in the enoxaparin group ( 70 patients ) met the criteria for the primary efficacy outcome ( relative risk with apixaban , 0.87 ; 95 % confidence interval [ CI ] , 0.62 to 1.23 ; P=0.44 ) . By day 30 , major bleeding had occurred in 0.47 % of the patients in the apixaban group ( 15 of 3184 patients ) and in 0.19 % of the patients in the enoxaparin group ( 6 of 3217 patients ) ( relative risk , 2.58 ; 95 % CI , 1.02 to 7.24 ; P=0.04 ) . CONCLUSIONS In medically ill patients , an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin . Apixaban was associated with significantly more major bleeding events than was enoxaparin . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00457002 . ) This study aim ed to determine the frequency of fatal pulmonary emboli in hospitalised medical patients by a retrospective necropsy review and prospect i ve non-interventional patient follow up study . The main outcome measure , necropsy proven fatal pulmonary embolism , was determined from 400 consecutive necropsy records and 200 consecutive medical inpatient episodes . Fatal pulmonary embolism was recorded in 29 of 400 necropsies ; 17 were medical patients . Thirty one of 200 consecutive medical patients died . Fourteen necropsies were performed and revealed pulmonary embolism as the cause of death in five patients . The incidence of necropsy proven fatal pulmonary embolism was therefore 2.5 % ( 95 % confidence intervals 0.8 % to 5.7 % ) . Therefore , one in 40 medical patients had pulmonary embolism recorded as the cause of death at necropsy . As the necropsy rate was only 45 % the incidence of fatal pulmonary embolism may be greater . There is , therefore , a need to perform more large prospect i ve studies to confirm the incidence of fatal pulmonary embolism in medical patients and to identify risk factors and effective antithrombotic prophylaxis BACKGROUND Hospitalized patients with medical illness are especially susceptible to the development of venous thromboembolism ( VTE ) . METHODS To improve our underst and ing of the demographics , comorbidities , risk factors , clinical presentation , prophylaxis , and treatment of hospitalized medical patients with deep vein thrombosis ( DVT ) , we evaluated hospitalized medical patients in a prospect i ve registry of 5,451 consecutive ultrasound-confirmed DVT patients at 183 institutions in the United States . RESULTS Of those patients who participated in the registry , 2,609 ( 48 % ) were hospitalized medical patients . Compared with 1,953 hospitalized nonmedical patients with DVT , medical patients with DVT experienced pulmonary embolism ( PE ) more often ( 22.2 % vs 15.5 % , respectively ; p < 0.0001 ) . However , medical patients in whom DVT developed had received VTE prophylaxis far less frequently than nonmedical patients ( 25.4 % vs 53.8 % , respectively ; p < 0.0001 ) . The underutilization of VTE prophylaxis among hospitalized medical patients extended to both pharmacologic and mechanical modalities . In a multivariable logistic regression analysis of all hospitalized VTE patients , status as a medical patient was negatively associated with receiving prophylaxis ( adjusted odds ratio , 0.47 ; 95 % confidence interval , 0.28 to 0.78 ) . CONCLUSIONS Hospitalized medical patients face " double trouble . " First , during hospitalization for a reason other than VTE , VTE prophylaxis is omitted in medical patients more often than in nonmedical patients . Second , when VTE develops as a complication of hospitalization , hospitalized medical patients experience PE more often . Further studies should focus on underst and ing why prophylaxis is often omitted in hospitalized medical patients and on improving its implementation in this vulnerable population PURPOSE The purpose of this investigation is to estimate the prevalence of acute pulmonary embolism ( PE ) in a general hospital , its frequency among patients who died , and the ability of physicians to diagnose PE antemortem . METHODS The prevalence of acute PE among 51,645 patients hospitalized over a 21-month period was assessed in 1 of the 6 clinical centers ( Henry Ford Hospital ) that participated in the collaborative study , prospect i ve investigation of pulmonary embolism diagnosis ( PIOPED ) . The diagnosis of PE was made by pulmonary angiography , or in those who did not undergo pulmonary angiography because they declined or were ineligible for r and omization to angiography in PIOPED , the diagnosis was based on the ventilation/perfusion ( V/Q ) lung scan . Based on data in PIOPED , PE was considered to be present in 87 % of patients with high probability V/Q scam interpretations , 30 % with intermediate probability interpretations , 14 % with low probability interpretations , and 4 % with nearly normal V/Q scans . RESULTS The estimated prevalence of acute PE in hospitalized patients was 526 of 51,645 ( 1.0 % ; 95 % confidence interval [ CI ] , 0.9 to 1.1 % ) . Based on extrapolated data from autopsy , PE was estimated to have caused or contributed to death in 122 of 51,645 ( 0.2 % ; 95 % CI , 0.19 to 0.29 % ) . Pulmonary embolism was observed at autopsy in 59 of 404 ( 14.6 % ; 95 % CI , 11.3 to 18.4 % ) . Among patients with PE at autopsy , the PE caused or contributed to death in 22 of 59 ( 37.3 % ; 95 % CI , 25.0 to 50.9 % ) and PE was incidental in 37 of 59 ( 62.7 % ; 95 % CI , 49.1 to 75.0 % ) . Among patients at autopsy who died from PE , the diagnosis was unsuspected in 14 of 20 ( 70.0 % ; 95 % CI , 45.7 to 88.1 % ) . Most of these patients had advanced associated disease . In these patients , death from PE occurred within 2.5 h in 13 of 14 ( 92.9 % ; 95 % CI , 66.1 to 99.8 % ) . CONCLUSION Pulmonary embolism is common in a general hospital . The prevalence of PE at autopsy has not changed over 3 decades . The frequency of unsuspected PE in patients at autopsy has not diminished . Even among patients who die from PE , the PE is usually unsuspected . Such patients , however , typically have advanced disease . Among moribund patients , incidental PE is rarely diagnosed . Patients who suffer sudden unexplained catastrophic events in the hospital are a group in whom the diagnosis might be suspected more frequently if physicians maintain a high index of suspicion |
2,333 | 24,497,229 | Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis .
There is evidence of less nephrotoxicity in children | BACKGROUND People with cystic fibrosis , who are chronically colonised with the organism Pseudomonas aeruginosa , often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations .
The properties of aminoglycosides suggest that they could be given in higher doses less often .
OBJECTIVES To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis . | BACKGROUND : There is evidence that administration of higher doses of aminoglycosides given less frequently improves the bactericidal effect and reduces the potential to cause side effects . To investigate this , a prospect ively r and omised open label therapeutic trial was undertaken in stratified groups of patients with cystic fibrosis to examine the efficacy and toxic potential of an aminoglycoside dosing regimen design ed to generate high peak drug concentrations at 12 hourly intervals compared with conventional dosing at eight hourly intervals . METHODS : Patients in group A received tobramycin eight hourly using a dose aim ed at generating a peak concentration of 10 mg/l with trough concentrations below 2 mg/l , and those in group B received the total daily dose required to achieve eight hourly target concentrations administered as two equal 12 hourly doses . Clinical outcomes measured and assessed included vestibular symptoms , hearing and renal function , length of hospital stay , readmission rate , and mortality . RESULTS : Twenty nine patients were recruited during a six month period , 20 to group A and nine to group B. The average peak tobramycin level was higher in group B ( 12.5 ( 2.2 ) mg/l ) than in group A ( 7.9 ( 1.9 ) mg/l ) , whilst the average trough level was higher in group A ( 0.8 ( 0.3 ) mg/l ) than in group B ( 0.5 ( 0.2 ) mg/l ) . There was a difference in the number of ototoxic events between patients in group A ( seven of 18 , 38.9 % ) and group B ( none of eight ) , but no difference was found in other outcome measures assessed . CONCLUSIONS : These results suggest that 12 hourly high peak aminoglycoside dosing may be less toxic than equivalent eight hourly dosing , without any apparent difference in efficacy OBJECTIVES Once-daily administration of aminoglycosides in cystic fibrosis ( CF ) patients is considered equally efficacious and potentially less nephrotoxic than dosing three times a day . However , the choice of the most suitable PK/PD index ( C(max)/MIC versus AUC(24)/MIC ) to ensure optimum clinical outcome in this patient population is not clear . PATIENTS AND METHODS In a single-centre , open , r and omized , controlled , non-blinded study 33 adult CF patients ( 20 females , 19 - 37 years ) were treated with intravenous tobramycin ( 10 mg/kg/day ) for 14 days given either as single dose once a day ( Q24 ; 17 patients ) or divided into three equal doses every 8 h ( Q8 ; 16 patients ) . Tobramycin serum concentrations and MICs for Pseudomonas aeruginosa were determined on days 1 and 14 . The clinical outcome parameter , correlated to PK/PD indices , was the percentage predicted forced expiratory volume in 1 s ( FEV(1)% pred . ) . RESULTS FEV(1)% pred . improved significantly for both treatments . There was a log-linear relationship between C(max)/MIC and FEV(1)% pred . and AUC/MIC and FEV(1)% pred . for both treatments . For equal values of AUC24/MIC , however , Q24 treatment provided better improvement in lung function than Q8 dosing , whereas C(max)/MIC did not show any dosing interval dependence . A statistically significant increase was observed for MIC ( day 1 ) versus MIC ( day 14 ) for Q24 treatment , however , no such difference was observed for Q8 treatment . CONCLUSIONS The most important PK/PD parameter for clinical outcome in CF patients was C(max)/MIC . Outcome prediction of AUC(24)/MIC was dependent on the regimen . The increase of P. aeruginosa resistance after once-daily administration is linked to a long dosing interval . More and larger studies are needed to optimize the dosing regimen for maximum clinical outcome with minimum resistance development Twenty-six patients with cystic fibrosis and pulmonary exacerbations were enrolled in a prospect i ve r and omized study to compare the efficacy of aminoglycosides ( tobramycin or netilmicin ) administered once daily ( 21 episodes , 5 with netilmicin , 16 with tobramycin ) and thrice daily ( 23 episodes , 2 with netilmicin , 21 with tobramycin ) , respectively . In addition , the patients received an anti-pseudomonal beta-lactam antibiotic . In the single-dose group the total daily dosage was 4.97 + /- 1.12 mg/kg ( total dosage per exacerbation : 74.55 mg/kg ) , compared to 9.60 + /- 2.70 mg/kg in the triple-dose group ( total dosage per exacerbation : 165.12 mg/kg ) . The mean peak and trough serum levels of the aminoglycoside were 8.31 + /- 1.76 mg/l and 0.18 + /- 0.10 mg/l , respectively in the single dose group compared to 6.12 + /- 1.30 mg/l and 0.58 + /- 0.31 mg/l in the triple dose group . Success of treatment , defined as decrease in leucocyte counts , normalization of elevated CRP-values , number of days in hospital and interval until next admission to hospital , was not different between both groups . We conclude that single daily dose of aminoglycosides was as efficacious as triple dose in our patients Aminoglycosides are often prescribed as part of the treatment regimen for acute pulmonary exacerbations due to their potent activity and low potential for development of resistance . Preliminary evidence from r and omized controlled trials in patients with cystic fibrosis ( CF ) suggests that once-daily administration of aminoglycosides results in similar efficacy and a low risk for toxicity compared with traditional dosing . The pharmacokinetics of aminoglycosides administered once daily in CF patients are currently not well described . In this study we compare the distribution and elimination patterns of traditional dosing ( 3.3 mg/kg q8h ) versus once-daily dosing ( 10 mg/kg q24h ) of tobramycin in six adult patients with CF . The pharmacokinetics of tobramycin administered either once daily or every 8 h were best described by a two-compartment model . No statistically significant differences in any of the pharmacokinetic parameter values between regimens were noted . The distribution phase half-lives of 32 and 24 min following the q8h and q24h regimens were longer than expected . The use of a one-compartment model requires clinical peak levels to be drawn 2 h after initiation of either a 30 min infusion for multiple daily dosing or a 60 min infusion with once-daily dosing , to ensure completion of the distribution phase . Our data indicate that a dose of 10 mg/kg/day provides post-distributional phase peak concentrations that achieve the desired goal for susceptible organisms ( > 20 mg/L ) and AUC(24 ) values at the upper end of the desired range ( 70 - 100 mg.h/L ) ABSTRACT We undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large r and omized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis ( the TOPIC study ) . All patients were eligible to have st and ard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz . High-frequency pure tone audiometry over 10 to 16 kHz was also performed with a subset of patients . Audiometry was undertaken at the start of tobramycin treatment , at the end of a 14-day course of treatment , and at follow-up 6 to 8 weeks later . We enrolled 244 patients , of whom 219 ( 125 children and 94 adults ) completed treatment . Nineteen patients were excluded from analysis due to abnormal baseline audiometry . Complete pre- and posttreatment st and ard audiological data were obtained for 168/219 patients . We found no significant differences in hearing thresholds when they were assessed at the baseline , at the end of treatment , and at follow-up 6 to 8 weeks later were compared . In addition , no significant differences in hearing thresholds were detected between treatment regimens . Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry . We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit , no measurable effect on hearing was apparent with either once- or three-times-daily treatment . Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy , as evidence d by the patients excluded from this study due to hearing loss , also requires further characterization Our objective was to compare the efficacy , safety , and microbiology of once-daily intravenous ( IV ) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa ( PA ) pulmonary exacerbations in cystic fibrosis ( CF ) . CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin ( Mono ) or conventional therapy with tobramycin/ceftazidime given 8-hourly ( Conv ) . The two longitudinal groups received therapy in a double-blind , r and omized manner over a period of 2 years . Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups . Results were assessed for both short-term changes ( efficacy and safety after 10 days of IV antibiotics during acute exacerbations ) and long-term changes ( efficacy , safety , and sputum microbiology between study entry and exit ) . Pulmonary function tests ( PFTs ) on admission were similar in both groups . After 10 days of IV antibiotics , absolute mean improvements in percent of predicted PFTs were 12.8 , 12.1 , and 13.7 for forced expiratory volume in 1 sec ( FEV(1 ) ) , forced vital capacity ( FVC ) , and forced expired flow between 25 - -75 % of FVC ( FEF(25 - -75 % ) ) in the Conv group ( n = 51 admissions ) compared to 10.6 , 9.9 , and 10.6 in the Mono group ( n = 47)(P<0.05 for all ) . Sixteen percent in the Conv group and 15 % of patients in the Mono group did not respond to therapy by day 10 . Long-term PFT patterns were similar for the Conv and Mono groups . The time between admissions did not differ . The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations ( MICs ) against PA from study entry to study exit ( P = 0.02 , n = 27 strains ) ; this failed to reach significance in the Conv group ( P = 0.08 , n = 25 ) . There was no significant increase in the number of isolates , with MIC > or = 8 mg/L in both groups . No short- or long-term changes in audiology or serum creatinine were found in either group . After 10 days of IV therapy , the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups ( P0.05 ) . This increase was greater in the Conv compared to the Mono group ( P < 0.05 ) . We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy . Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy . Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation , including the impact on susceptibility of PA to tobramycin The efficacy and toxicity of a shortened tobramycin dosing interval in the treatment of exacerbations of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis patients were evaluated prospect ively . Patients ages 13 to 30 years received 34 treatment courses and were r and omized by pairs to receive tobramycin administered either every 6 or 8 hours . Peak serum concentrations were adjusted to 8 to 10 micrograms/ml ; thus a larger total daily dosage was administered to patients receiving tobramycin every 6 hours . The shorter dosing interval was associated with better pulmonary function at follow-up and significantly longer time before next hospital admission for a pulmonary exacerbation . During the study hospitalization there were no differences in pulmonary function tests , clinical score , sputum carriage of P. aeruginosa , toxicity or necessary length of hospitalization . A 6-hour tobramycin dosing interval was more efficacious than an 8-hour dosing interval in the treatment of cystic fibrosis patients Although there are reports of cases of acute renal failure occurring in cystic fibrosis ( CF ) patients , usually in association with the use of nephrotoxic antibiotic therapy , there have been no studies of renal function in this patient group . We hypothesized that long-term use of intravenous ( IV ) nephrotoxic antibiotics ( aminoglycosides and colistin sulphomethate ) may contribute to renal disease in CF patients . In a prospect i ve study , we assessed creatinine clearance as an index of renal function with two techniques ( 24-hr urine collection s and the Cockroft-Gault formula ) in a group of 80 stable adult CF out patients chronically infected with Pseudomonas aeruginosa but with no history of preceding renal disease . Using a multiple linear regression model , we evaluated their renal function in terms of their lifetime IV use of aminoglycosides and colistin . Between 31 % ( Cockroft-Gault formula method ) and 42 % ( 24-hr urine collection method ) of patients had a creatinine clearance below normal range . Using either method , there was a strong correlation between aminoglycoside use and diminishing renal function ( r=- 0.32 , P=0.0055 ) , which was potentiated by the coadministration of colistin ( r=- 0.42 , P < 0.0002 ) . However , there was no correlation with colistin when used in combination with other antibiotics alone ( r=0.18 , P = NS ) . Repeated IV aminoglycoside use in CF is associated with long-term renal damage . Although this effect is potentiated by colistin , colistin on its own in moderate doses does not appear to be nephrotoxic . IV aminoglycosides should be used cautiously in CF patients , with regular monitoring of renal function BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset . CONCLUSIONS In patients with cystic fibrosis , the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms , result ed in slight improvement in pulmonary function , and was well tolerated The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose . Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy . Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing , and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens . Dogs given gentamicin , tobramycin , or netilmicin once daily , with maximum serum concentrations of greater than 100 mg/liter , had less nephrotoxicity than dogs given continuous infusions . Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter . Intermittent dosing of aminoglycosides , causing infrequent large maximum serum concentrations , may be less toxic and equally efficacious as frequent dosing |
2,334 | 26,907,163 | The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores .
The impact of ESAs on AEs and survival remains highly uncertain , although point estimates are lower , confidence intervals are wide and not statistically significant .
Base-case incremental cost-effectiveness ratios ( ICERs ) for ESA treatment compared with no ESA treatment ranged from £ 19,429 to £ 35,018 per QALY gained , but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs , including the possibility of overall health disbenefit .
ESAs could be cost-effective when used closer to licence , but there is considerable uncertainty , mainly because of unknown impacts on overall survival . | BACKGROUND Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life .
Erythropoiesis-stimulating agents ( ESAs ) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia ( CIA ) .
OBJECTIVE To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment ( specifically chemotherapy ) . | Anemia , one of the most common complications of cancer chemotherapy , has been managed with red blood cell ( RBC ) transfusions . As an alternative , the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy . To estimate the value that cancer patients place on the drug , an economic analysis using the concept of willingness to pay ( WTP ) was conducted ABSTRACT Objective : To compare the cost-effectiveness of epoetin alfa ( EPO ) and darbepoetin alfa ( DARB ) for the treatment of chemotherapy-induced anemia ( CIA ) , using dosing regimens approved by the FDA ( EPO 40 000 U once weekly and DARB 2.25 mcg/kg once weekly ) . Methods : The study compared published results of two double-blind , r and omized , phase III trials one utilizing EPO ( N = 166 ) and the other , DARB ( N = 367 ) . Patients in both trials had similar baseline characteristics . Effectiveness was measured as the proportion of EPO or DARB patients who were successfully treated ( i.e. , did not require blood transfusion ) during weeks 0–16 and 5–16 , respectively . Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost ( WAC ) and average drug utilization over 16 weeks . Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness . Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs . Results : Estimated drug costs over 16 weeks were $ 9039 for EPO and $ 13 555 for DARB . During weeks 5–16 , 85 % of EPO patients and 73 % of DARB patients were successfully treated , result ing in average cost-effectiveness ratios of $ 106 for EPO and $ 186 for DARB per one per cent of successfully treated patients . A 33 % reduction in DARB WAC was required to achieve the same drug costs as for EPO . Conclusions : Utilizing FDA -approved doses , EPO was found to result in lower drug costs and better treatment success when compared to DARB . Hence , EPO is a dominant alternative compared to DARB for the treatment of CIA . The analyses presented here are not without limitations . Specifically , although the studies were comparable , patients were ultimately drawn from different population Previous phase I-II clinical trials have shown that recombinant human erythropoietin ( rHuEpo ) can ameliorate anemia in a portion of patients with multiple myeloma ( MM ) and non-Hodgkin 's lymphoma ( NHL ) . Therefore , we performed a r and omized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo . A total of 146 patients who had hemoglobin ( Hb ) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial . Patients were r and omized to receive 1,000 U ( n = 31 ) , 2,000 U ( n = 29 ) , 5,000 U ( n = 31 ) , or 10,000 U ( n = 26 ) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy ( n = 29 ) . Of the patients , 84 suffered from MM and 62 from low- to intermediate- grade NHL , including chronic lymphocytic leukemia ; 116 of 146 ( 79 % ) received chemotherapy during the study . The mean baseline Hb level was 9.4 + /- 1.0 g/dL. The median serum Epo level was 32 mU/mL , and endogenous Epo production was found to be defective in 77 % of the patients , as judged by a value for the ratio of observed-to-predicted serum Epo levels ( O/P ratio ) of < or = 0.9 . An intention-to-treat analysis was performed to evaluate treatment efficacy . The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 ( P = .57 ) , 0.22 ( P = .05 ) , 0.43 ( P = .01 ) , and 0.58 ( P = .0001 ) g/dL in the 1,000 U , 2,000 U , 5,000 U , and 10,000 U groups , respectively ( P values versus control ) . The probability of response ( delta Hb > or = 2 g/dL ) increased steadily and , after 8 weeks , reached 31 % ( 2,000 U ) , 61 % ( 5,000 U ) , and 62 % ( 10,000 U ) , respectively . Regression analysis using Cox 's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo , whereas only one quarter of those with adequate Epo levels did so . Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50 % of these patients are expected to respond to rHuEpo . Thus , rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production . From a practical point of view , we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels , whereas the choice of the initial dosage should be based on residual marrow function OBJECTIVE To compare the steady-state pharmacokinetics and pharmacodynamics following multiple subcutaneous administration of a new erythropoiesis stimulating agent ( HX575 , Binocrit , S and oz GmbH , Holzkirchen , Germany ) with that of epoetin beta ( NeoRecormon , Roche Ltd. , Welwyn Garden City , UK ) . METHODS An open , r and omized , parallel group study was conducted in 80 healthy adult males . Subjects were r and omized to multiple subcutaneous doses of 100 IU/kg body weight of HX575 or epoetin beta three-times-weekly for 4 weeks . Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay ( ELISA ) and pharmacokinetic parameters for the two treatments were compared . The time course and area under the effect curve ratios of hematological characteristics were used as surrogate parameters for efficacy evaluation . RESULTS The pharmacokinetic profiles after multiple doses were similar for both treatments . HX575 was bioequivalent to epoetin beta with respect to the rate and extent of exposure of exogenous epoetin , as indicated by the ratios ( 90 % confidence intervals ) of AUC(tau ) ( 96.1 ( 86.4 - 106.9 ) ) and C(max , ss ) ( 98.5 ( 85.2 - 113.9 ) ) . The hematological profiles of both treatments were similar as determined from the population mean curves and the AUEC(Hb ) ratio ( 90 % confidence interval ] ( 99.2 ( 97.7 - 100.7 ) ) , the primary endpoint of this study . Study medication was well tolerated with no clinical ly relevant differences between safety profiles of the treatments . Anti-epoetin antibodies were not detected at any time . CONCLUSIONS HX575 and epoetin beta were bioequivalent with respect to their steady-state pharmacokinetic profile and pharmacodynamic action . These results support the conclusion that HX575 and epoetin beta will be equally efficacious and may be interchangeable as therapy Patients with breast cancer treated with adjuvant chemotherapy experience not only fatigue and menopausal symptoms but also documented cognitive dysfunction and reduced capacity to carry out activities of daily living . The role of epoetin alfa in improving cognition and functional capacity was assessed in a large r and omized trial through patient self-reported outcomes . Patients with breast cancer ( N = 354 , adjuvant and metastatic ) undergoing chemotherapy were r and omized in a 1:1 ratio to receive epoetin alfa ( 40,000 IU once weekly ) or the st and ard of care ( SOC ) . Change in patient-reported Health Utilities Index Mark 3 ( HUI3 ) from baseline to week 12 was compared between the epoetin alfa and SOC groups . In addition , correlations between the disease-nonspecific HUI3 utility scale and the cancer-specific quality of life instrument Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) and Fatigue subscales were assessed . Epoetin alfa treatment significantly improved HUI3 scores compared with patients receiving SOC ( P = 0.036 ) . Three subscales within HUI3 were also significantly better for epoetin alfa-treated patients ( emotion , P = 0.048 ; ambulation , P = 0.048 ; and cognition , P = 0.02 ) . Moreover , a strong correlation ( P = 0.0001 ) exists between the disease-nonspecific utility scale HUI3 and the disease-specific FACT-An and FACT-Fatigue scales in terms of overall scores and score changes . The findings of the study demonstrate for the first time in patients with breast cancer that epoetin alfa significantly enhances functional well-being , which translates into significantly better utility scores . In addition , epoetin alfa also significantly improved cognitive function of women undergoing chemotherapy , and this could have an important impact on their lives from a societal perspective Health-related quality of life ( HrQOL ) assessment s are gaining importance as outcome measures in cancer clinical trials . A recently published clinical trial reported statistically significant ( P<0.001 ) increases in haemoglobin ( Hb ) levels and significantly ( P<0.01 ) increased HrQOL scores following the administration of recombinant human erythropoietin ( r-HuEPO , epoetin alfa ) versus placebo to anaemic cancer patients who received non-platinum chemotherapy . This study employed five cancer-specific HrQOL instruments . Hb and HrQOL data from this trial were analysed to estimate the minimally important difference ( MID ) in HrQOL measures that could be interpreted as clinical ly meaningful , with Hb level selected as the best external st and ard . Patients were assigned to two groups : improved ( Hb increases of > /=1 g/dL ) or stable ( change in Hb of-1 g/dL to < 1 g/dL ) . The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group . By this analysis , the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinical ly important for all Hb-sensitive , cancer-specific HrQOL evaluations . Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinical ly significant . These analyses were repeated using a data set from a separate clinical trial , which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre , double-blind study were clinical ly important . These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials Background HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway . Therefore , in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa , the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations . Methods An open , r and omised , parallel group study was conducted in 80 healthy adult males . Subjects were r and omised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks . Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared . The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation . Results The haematological profiles of both treatments were similar , as determined from their population mean curves and the AUECHb ratio and 90 % confidence interval ( 99.9 % [ 98.5–101.2 % ] ) , the primary pharmacodynamic endpoint of this study . The pharmacokinetic parameters after the treatments showed minor differences after single dosing , but not at steady state doses . After multiple doses , HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin ( AUCτ ratio and 90 % confidence interval : 89.2 % [ 82.5–96.2 % ] ) . Study medication was well tolerated with no clinical ly relevant differences between safety profiles of the treatments . Anti-epoetin antibodies were not detected . Conclusion HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action . This supports the conclusion that HX575 and the comparator epoetin alfa , when administered intraveneously , will be equally efficacious and may be interchangeable as therapy PURPOSE Erythropoietin , an oxygen-regulated glycoprotein hormone , is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [ erythropoietin receptor ( EPOR ) ] . The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients . However , in a recent r and omized , placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck , erythropoietin treatment was associated with poorer locoregional progression-free survival . The purpose of our study was to determine whether EPOR and its lig and erythropoietin are expressed in primary head and neck cancer . We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia , an important factor involved in resistance to radiation treatment , tumor aggressiveness , and poor prognosis . EXPERIMENTAL DESIGN Twenty-one patients received an i.v . infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies . Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding . RESULTS EPOR expression was present in tumor cells in 97 % of the biopsies . Coexpression of erythropoietin was observed in 90 % of biopsies . Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors , but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding . CONCLUSIONS The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer . The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia PURPOSE This open-label , r and omized phase III study was design ed to investigate the effects of erythropoietin alfa ( EPO ) in addition to adjuvant chemotherapy and pelvic radiotherapy ( CRT ) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy . PATIENTS AND METHODS Two hundred fifty-seven patients were r and omly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy ( CRT group ) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO ( CRT + EPO group ) . The primary end point was recurrence-free survival ( RFS ) . Secondary end points included overall survival ( OS ) , change in hemoglobin levels , and safety , including thromboembolic events . RESULTS The estimated 5-year RFS rates were 78 % for patients receiving CRT + EPO and 70 % for patients receiving CRT . There was no statistically significant difference in RFS , although a trend favoring patients treated with CRT + EPO was observed ( hazard ratio [ HR ] , 0.66 ; 95 % CI , 0.39 to 1.12 ; log-rank P = .06 ) . Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease ( HR , 0.39 ; 95 % CI , 0.18 to 0.85 ; P = .014 ) or patients with complete resection ( HR , 0.55 ; 95 % CI , 0.31 to 0.98 ; P = .039 ) . OS was similar in both groups ( HR , 0.88 ; 95 % CI , 0.51 to 1.50 ; log-rank P = .63 ) . Patients treated with EPO maintained higher hemoglobin levels throughout CRT . No significant differences in safety profiles were observed between the two groups . Incidence of thrombovascular events was low ( 2 % ) and comparable between both groups . CONCLUSION This study confirms that EPO can be added safely to CRT in patients with cervical cancer , but it failed to demonstrate a significant benefit in RFS and OS PURPOSE To exp and on our experience with the combination of paclitaxel , fluorouracil , hydroxyurea , and twice daily irradiation ( T-FHX ) and to assess the impact of weekly administration of erythropoietin ( r-HuEpo ) on transfusion requirements , we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and r and omized patients to receive weekly doses of r-HuEpo . PATIENTS AND METHODS A total of 90 patients with locally advanced head and neck cancers ( stage IV , 96 % ; N(2)/N(3 ) , 66 % ) were treated on a regimen of 1-h infusion of paclitaxel ( 100 mg/m(2)/day , day 1 ) , 120-h infusion of 5-fluorouracil ( 600 mg/m(2)/day , days 0 - 5 ) ; hydroxyurea 500 mg p.o . every 12 h for 11 doses ; and radiation 150cGy bid , days 1 - 5 of each 14-day cycle repeated for five cycles over 10 weeks ( 7200 - 7500 cGy ) . Before initiating therapy , patients were r and omized to receive r-HuEpo 40,000 IU s.c . once weekly . RESULTS At median follow-up of 40 months , 3-year progression-free survival is 62 % , locoregional control is 84 % , and systemic control is 79 % . Overall survival is 59 % . Anemia , leucopenia , dermatitis , and mucositis were the most frequent grade 3 or 4 toxicities . Patients r and omized to erythropoietin experienced less grade 2/3 anemia ( 52 versus 77 % ; P = 0.02 ) , but transfusion requirements were not significantly different . CONCLUSIONS T-FHX is an active and tolerable regimen inducing local tumor control and promising survival with organ preservation in high-risk patients . One h infusion of paclitaxel simplified the regimen without compromising efficacy . Addition of erythropoietin does not reduce the need for transfusion with this nonplatinum-containing regimen . T-FHX should be advanced to a r and omized trial and compared with a cisplatin-based concomitant regimen Experimental evidence suggests that the hypoxic fraction in a solid tumor may increase its malignant potential and reduce its sensitivity towards non-surgical treatment modalities ( e.g. st and ard irradiation , certain anticancer agents ) . However , the clinical importance of tumor hypoxia remains uncertain since valid methods for the routine measurement of intratumoral O2-tensions in patients have so far been lacking . A clinical ly applicable st and ardized procedure has been established which enables the determination of intratumoral oxygen tensions in advanced cervical cancers by use of a computerized polarographic needle electrode histography system . Tumor oxygenation as measured by this method represents a novel tumor feature which can be individually determined for each tumor and which is independent from other known oncological parameters . The results of an interim analysis of an open prospect i ve clinical trial to evaluate the prognostic significance of tumor oxygenation based on the survival data of the first 31 patients are presented . Fifteen patients have been treated by primary radiation , 11 patients received multimodality therapy including irradiation . After a median follow-up of 19 months ( range 5 - 31 months ) , Kaplan-Meier-life table analysis showed significantly lower survival and recurrence-free survival for patients with a median pO2 of < or = 10 mmHg compared to those with better oxygenated tumors ( median pO2 > 10 mmHg ) . The Cox proportional hazards model revealed that the median pO2 and the clinical stage according to the FIGO are independent , highly significant predictors of survival and recurrence-free survival . We conclude from these preliminary results that tumor oxygenation as determined with this st and ardized procedure appears to be a new independent prognostic factor influencing survival in advanced cancer of the uterine cervix Background Several studies have shown that darbepoetin alfa , an erythropoiesis-stimulating agent ( ESA ) , can reduce transfusions and increase hemoglobin ( Hb ) levels in patients with chemotherapy-induced anemia ( CIA ) . Recent safety concerns , however , have prompted changes to ESA product information . In the European Union and United States , ESA therapy initiation for CIA is now recommended at a Hb level ≤10 g/dL. The present exploratory analysis examined how ESA initiation at this Hb level may impact patient care . Methods Data from a phase 3 r and omized trial were retrospectively reanalyzed . CIA patients with nonmyeloid malignancies were r and omized 1:1 to 500 mcg darbepoetin alfa every three weeks ( Q3W ) or 2.25 mcg/kg darbepoetin alfa weekly ( QW ) for 15 weeks . A previously published report from this trial showed Q3W dosing was non-inferior to QW dosing for reducing transfusions from week 5 to end-of-the-treatment period ( EOTP ) . In the present analysis , outcomes were reanalyzed by baseline Hb < 10 g/dL and ≥10 g/dL. Endpoints included transfusion rates , Hb outcomes , and safety profiles . Results This study reanalyzed 351 and 354 patients who initiated ESA therapy at a baseline Hb of < 10 g/dL or ≥10 g/dL , respectively . From week 5 to EOTP , the estimated Kaplan-Meier transfusion incidence ( Q3W vs QW ) was lower in the ≥10 g/dL baseline-Hb group ( 14 % vs 21 % ) compared with the < 10 g/dL baseline-Hb group ( 36 % vs 41 % ) . By week 5 , the ≥10 g/dL baseline-Hb group , but not the < 10 g/dL baseline-Hb group , achieved a mean Hb ≥11 g/dL. The Kaplan-Meier estimate of percentage of patients ( Q3W vs QW ) who achieved Hb ≥11 g/dL from week 1 to EOTP was 90 % vs 85 % in the ≥10 g/dL baseline-Hb group and 54 % vs 57 % in the < 10 g/dL baseline-Hb group . Both baseline-Hb groups maintained mean Hb levels < 12 g/dL and had similar safety profiles , though more patients in the ≥10 g/dL baseline-Hb group reached the threshold Hb of ≥13 g/dL. Conclusion In this exploratory analysis , darbepoetin alfa Q3W and QW raised Hb levels and maintained mean Hb at < 12 g/dL in both baseline-Hb groups . The ≥10 g/dL baseline-Hb group had fewer transfusions and faster anemia correction . Additional studies should prospect ively evaluate the relationship between Hb levels at ESA initiation and outcomes .Trial Registration Clinical Trials.gov Identifier NCT00118638 Aim : To compare the steady-state pharmacokinetics and pharmacodynamics ( PK/PD ) of two erythropoesis-stimulating agents ( ESA ) , HX575 ( Binocrit ® , S and oz GmbH , Holzkirchen , Germany ) , human recombinant epoetin alfa approved as the first biosimilar ESA , and a comparator epoetin alfa , following multiple subcutaneous administrations . Methods : An open , r and omized , parallel group study was conducted in 80 healthy adult males . Subjects were r and omized to multiple subcutaneous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa 3 times weekly for 4 weeks . Results : The hematological profiles of both treatments were similar , as determined from the population mean curves and area under the effect curve ( AUEC ) ratios . HX575 met the predefined biosimilarity criteria with respect to the ratio and 90 % confidence interval of the AUECHb ( 98.9 % [ 97.7–100.2 % ] ) , the primary PD endpoint . The PK of the two treatments were also similar as shown by the AUC0–48 ratios and 90 % confidence intervals , 94.3 % [ 84.7–105.0 % ] and 96.9 % [ 88.2–106.5 % ] , respectively . Study medication was well tolerated and neutralizing anti-epoetin antibodies were not detected . Conclusions : HX575 and the comparator epoetin alfa were bioequivalent with respect to their PK/PD , supporting the conclusion that both , when administered subcutaneously , will be equally efficacious and may be interchangeable as therapy Introduction Recombinant human erythropoietin ( r-HuEPO ) is used to treat symptomatic anaemia due to chemotherapy . A new r-HuEPO , Epoetin theta ( Eporatio ® ) , was investigated and compared to placebo and Epoetin beta in a r and omised , double-blind clinical trial in adult cancer patients receiving platinum-based chemotherapy , using a fixed weekly starting dose of 20,000 IU Epoetin theta . The primary efficacy endpoint was the responder rate ( complete Hb response , Hb increase ≥ 2 g/dL ) . Research Design and Methods 223 patients were r and omised to s.c . treatment for 12 weeks with either Epoetin theta ( n = 76 ) once per week , Epoetin beta ( n = 73 ) three times per week or placebo ( n = 74 ) . The starting dose was 20,000 IU once weekly Epoetin theta or 450 IU/kgBW per week Epoetin beta administered in 3 equal weekly doses . Results In the Epoetin theta group were significantly more responders than in the placebo group ( 65.8 vs. 20.3 % , P < 0.0001 ) . Epoetin beta was also more effective than placebo ( 71.2 vs. 20.3 % , P < 0.0001 ) . The mean weekly dose at the time of complete Hb response was lower in the Epoetin theta group ( 30,000 IU ) than in the Epoetin beta group ( 42,230 IU ) . Epoetin theta was clearly more effective than placebo . Conclusion This small study showed , that Epoetin theta is a safe and effective treatment of symptomatic anaemia due to platinum-based chemotherapy in cancer patients Summary Anaemia commonly occurs in cancer patients receiving chemotherapy , often necessitating blood transfusion . This multicentre study was design ed to evaluate the efficacy and safety of epoetin α in preventing the decline in haemoglobin ( Hb ) level , and to determine whether the transfusion requirement could be reduced , in patients receiving 4–6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer ( SCLC ) . A total of 130 non-anaemic SCLC patients were r and omized to receive no additional treatment ( n = 44 ) , epoetin α 150 IU kg–1 subcutaneously ( s.c . ) three times a week ( n = 42 ) or 300 IU kg–1 s.c . three times a week ( n = 44 ) . Reductions in epoetin α dosage were made during the study if Hb level increased to > 15 g dl–1 . The mean weekly dosage was 335 and 612 IU kg–1 , respectively , in the two active treatment groups . Significantly fewer ( P < 0.05 ) epoetin α-treated patients experienced anaemia ( Hb < 10 g dl–1 ) during the course of chemotherapy ( 300 IU kg–1 , 39 % ; 150 IU kg–1 , 48 % ; untreated , 66 % ) . This was reflected in the significantly lower number of treated patients transfused [ 300 IU kg–1 , 20 % ( P < 0.001 ) ; 150 IU kg–1 , 45 % ( P < 0.05 ) ; untreated , 59 % ] . Epoetin α was well-tolerated , and there was no evidence of sustained , clinical ly significant , hypertension . In summary , epoetin α is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P < .0001 ) . After 12 and 16 weeks of treatment , QOL significantly improved in the epoetin beta group compared with placebo ( P < .05 ) ; this improvement correlated with an increase in Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL PURPOSE Recombinant human erythropoietin ( rHuEPO ) represents an attractive alternative to red blood cell ( RBC ) transfusions for the treatment of chemotherapy-induced anaemia . This prospect i ve , controlled study evaluated the safety and efficacy of rHuEPO in reducing RBC transfusion requirements in patients receiving platinum-based chemotherapy . PATIENTS AND METHODS Patients with histologically proven malignancies , haemoglobin ( Hb ) values < 10.5 g/dl , and receiving platinum-based chemotherapy were r and omised to either 150 IU/kg of rHuEPO subcutaneously ( s.c . ) x3/week ( group A ) , or simple follow-up plus RBC transfusions upon indication ( group B ) . All patients received 200 mg of elementary iron ( Fe ) daily . RESULTS A total of 47 patients were r and omised to either group A ( n=24 ) or the control group B ( n=23 ) . There was a statistically significant increase of Hb ( p < 0.0002 ) and haematocrit ( Ht ) ( p < 0.002 ) in group A patients compared to the control group B. The levels of Hb in group A patients increased significantly with each chemotherapy cycle number . There was a statistically significant ( p < 0.04 ) difference in the number of transfusions between the two groups , with only 37.5 % of group A patients requiring a RBC transfusion at any time during the study , compared to all patients ( 100 % ) in group B. CONCLUSIONS Administration of rHuEPO is an effective intervention for the management of chemotherapy-induced anaemia , significantly reducing RBC transfusion requirements in patients receiving platinum-based chemotherapy . Hb and Ht levels proved reliable indicators for response to rHuEPO treatment This multicentre , open-label , controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life ( QOL ) parameters in 182 anaemic ( Hb⩽12 g dl−1 ) ovarian cancer patients receiving platinum chemotherapy . Patients were r and omised 2 : 1 to receive epoetin alfa 10 000–20 000 IU three times weekly plus best st and ard treatment ( BST ) or BST only . Main study end points were changes from baseline in haemoglobin ( Hb ) level , transfusion requirements , and QOL . For the epoetin alfa group , mean Hb increased by 1.8 g dl−1 by weeks 4–6 and was significantly increased from baseline through study end ( P<0.001 ) . The mean change in Hb from baseline was significantly ( P<0.001 ) greater for epoetin alfa than BST patients at all postbaseline evaluations . Significantly fewer epoetin alfa than BST patients required transfusion(s ) after the first 4 weeks of treatment ( 7.9 vs 30.5 % ; P<0.001 ) . Also , significant ( P⩽0.04 ) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores ( Energy Level , Ability to Do Daily Activities , Overall QOL ) and the median average CLAS score during chemotherapy . These findings support use of epoetin alfa to increase Hb levels , reduce transfusion use , and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy BACKGROUND Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer . Strategies to improve efficacy include the use of anthracyclines , taxanes , and intensified dose with bone marrow support . PATIENTS AND METHODS Patients received neoadjuvant epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) followed by paclitaxel 175 mg/m(2 ) ( EC→T ) , each 3-weekly for four cycles ( n = 370 ) , or epirubicin 150 mg/m(2 ) followed by paclitaxel 225 mg/m(2 ) with pegfilgrastim followed by CMF ( cyclophosphamide 500 mg/m(2 ) , methotrexate 40 mg/m(2 ) , fluorouracil 600 mg/m(2 ) ) on days 1 and 8 ( E(dd)→T(dd)→CMF ) , each 2-weekly and for three cycles ( n = 363 ) . Patients were r and omly allocated to either simultaneous darbepoetin alfa ( DA ) ( n = 356 ) or none ( n = 377 ) . RESULTS Pathological complete response ( pCR ) rate ( breast ) was higher with E(dd)→T(dd)→CMF , 18.7 % versus 13.2 % with EC→T ; P = 0.043 , ypT0/Tis ; ypN0 was reported in 20.9 % versus 14.3 % respectively ; P = 0.019 . Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate . Mean hemoglobin values maintained higher with DA ( 13.6 versus 12.6 g/dl ) . E(dd)→T(dd)→CMF regimen showed more grade 3 - 4 mucositis , sensory neuropathy , and neurological complaints . Thromboembolic events were more frequent on DA ( 3 % versus 6 % ; P = 0.055 ) . CONCLUSION Dose-dense and -intensified neoadjuvant chemotherapy with E(dd)→T(dd)→CMF was potentially superior to EC→T in terms of pCR . Primary use of DA did not affect pCR BACKGROUND In the United States , darbepoetin alfa ( Aranesp ) is often used to treat patients with chemotherapy-induced anemia using weekly or every-2-week administration schedules . In Europe , darbepoetin alfa is used either weekly or in every-3-week dosing . The every-3-week schedule can be synchronized with many chemotherapy regimens , result ing in fewer visits and reducing burden to patients , but the safety and efficacy of this regimen have not been clear . METHODS A r and omized , double-blind , double-dummy , active-controlled phase 3 trial was performed in 110 European centers . Eligible patients ( age > or = 18 years ) were anemic ( hemoglobin level < 11 g/dL ) , had a nonmyeloid malignancy , and were to receive at least 12 weeks of chemotherapy . Patients were r and omly assigned 1:1 to darbepoetin alfa treatment every 3 weeks ( 500-microg dose ) or weekly ( 2.25-microg/kg ) for 15 weeks . We compared red blood cell transfusion incidence among the two arms from week 5 to the end of the treatment phase using a noninferiority study design . Noninferiority was determined if the upper limit of the 95 % confidence interval ( CI ) for the difference in blood transfusions between groups , calculated using Kaplan-Meier methods , did not exceed 12.5 % , a margin based on previous placebo-controlled studies . RESULTS A total of 705 patients were r and omly assigned , and 672 remained in the study at week 5 . Fewer patients in the every-3-week arm than in the weekly arm received blood transfusions from week 5 to the end of the treatment phase ( unadjusted Kaplan-Meier estimates = 23 % versus 30 % , difference = -6.8 % ; 95 % CI = -13.6 to 0.1 ) . Percentages of patients achieving the target hemoglobin level ( > or = 11 g/dL , consistent with evidence -based practice guidelines ) were 84 % ( every 3 weeks ) and 77 % ( weekly ) . The frequency of cardiovascular/thromboembolic adverse events was 8 % in both groups , and safety was comparable . CONCLUSIONS Patients with chemotherapy-induced anemia can safely and effectively be treated with 500 microg of darbepoetin alfa every 3 weeks Background Chemotherapy-induced anemia ( CIA ) is responsive to treatment with erythropoiesis-stimulating agents ( ESAs ) such as darbepoetin alfa . Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery . Methods This phase 2 , 25-week , open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule ( every 2 or 3 weeks ) in patients with CIA . Patients were r and omized 1:1 to an extended dosing schedule ( EDS : darbepoetin alfa 300 μg Q2W if chemotherapy was QW , Q2W , or Q4W or darbepoetin alfa 500 μg Q3W if chemotherapy was Q3W ) or weekly ( 150 μg QW regardless of chemotherapy schedule ) . Stratification factors included chemotherapy cycle length , screening hemoglobin ( < 10 g/dL vs. ≥10 g/dL ) , and tumor type ( lung/gynecological vs. other nonmyeloid malignancies ) . The primary endpoint was change in hemoglobin from baseline to Week 13 . Results Seven hundred fifty-two patients ( 374 QW patients ; 378 EDS patients ) received ≥1 dose of darbepoetin alfa and were included in the analysis . Demographics and disease state were similar between groups . Seventy-one percent of patients in the EDS group and 76 % in the QW group achieved the target hemoglobin of ≥11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin ( baseline to Week 13 ) between the QW and the EDS groups ( -0.04 g/dL ; 95 % confidence interval : -0.26 , 0.17 g/dL ) . The upper limit of the 95 % confidence interval was less than the prespecified limit of < 0.75 g/dL , supporting noninferiority of the EDS dosing schedule . Reported adverse events were similar between groups . A slight increase in transfusions was reported in the QW group . Conclusion Darbepoetin alfa , when administered synchronously with chemotherapy , on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events . This study provides prospect i ve data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules . Trial registration Clinical Trials.gov Identifier NCT00144131 PURPOSE To determine whether weekly epoetin alfa could improve hemoglobin ( HgB ) levels , reduce RBC transfusions , and improve quality of life ( QOL ) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy . PATIENTS AND METHODS This double-blind , placebo-controlled study r and omly assigned patients to placebo or epoetin alfa ( Ortho Biotech , Bridgewater , NJ ) 40,000 U subcutaneous weekly for 16 weeks . QOL , HgB , and RBC transfusions were measured pretreatment and monthly . RESULTS The study accrued 344 patients ; 330 were assessable for efficacy and 305 were assessable for QOL . Placebo-treated patients had a mean increase in HgB of 0.9 g/dL ( range , -3.8 to + 5.3 ) compared with 2.8 g/dL ( range , -2.2 to + 7.5 ) for epoetin-treated patients ( P < .0001 ) . During the study , 31.7 % of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7 % of epoetin-treated patients ( P < .0001 ) . The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6 % and 25.3 % ( P = .005 ) , respectively . The placebo group received 256 units of RBCs compared with 127 units in the epoetin group ( P < .0001 ) . The incidence of toxicity in the groups was similar . Changes in the average QOL scores from baseline to the end of the study were similar in the two groups ( P = not significant ) . The HgB responders ( irrespective of treatment arm ) had a mean change in Functional Assessment of Cancer Therapy ( FACT ) fatigue score from a baseline of + 5.1 compared with -2.1 for the nonresponders ( P = .006 ) . CONCLUSION Epoetin alfa significantly improved HgB and reduced transfusions in this patient population . These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia PURPOSE We report on a clinical trial developed to compare four different instruments that provide overall quality -of-life ( QOL ) scores , ranging from a simple , one-item instrument to more detailed instruments . Two issues addressed were ( 1 ) Will QOL tools suffer from missing data when used in a community-based cooperative group setting ? , and ( 2 ) Are there additional data generated by a more detailed multiitem instrument over that provided by a single-item global QOL question ? MATERIAL S AND METHODS A four-arm r and omized trial was design ed to compare four instruments that provide overall QOL scores in patients with advanced colorectal cancer . Patients and physicians completed the single-item Spitzer Uniscale ( UNISCALE ) at baseline and monthly . Patients were r and omly assigned to complete , in addition , either the 22-item Functional Living Index-Cancer ( FLIC ) , the five-item Spitzer QOL index ( QLI ) , a picture-face scale ( PICT ) , or nothing else . RESULTS A total of 128 patients were r and omized . Greater than 90 % complete QOL data were obtained . There was strong correlation , concordance , and criterion-related validity among all four patient-completed tools . The UNISCALE had a greater decrease over time than did the FLIC ( P=.005 ) , which suggests a greater sensitivity ; the UNISCALE was similar to the QLI and the PICT in this regard . Physicians provided lower UNISCALE scores than patients . Results supported the hypothesis that QOL is prognostic for survival . CONCLUSION Patients can effectively complete QOL tools in a cooperative group setting with proper education of health care providers and patients . A simple single-item tool ( UNISCALE ) appears to be appropriate to obtain a measure of overall QOL PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer Background The purpose of this study was to evaluate the safety and efficacy of epoetin alfa ( EPO ) at an initial dose of 60,000 Units ( U ) once weekly ( QW ) followed by extended dosing of 80,000 U every 3 weeks ( Q3W ) in patients with chemotherapy-induced anemia ( CIA ) . Material s and methods Anemic patients ( hemoglobin [ Hb ] ≤ 11 g/dl ) receiving Q3W chemotherapy for nonmyeloid malignancy were enrolled in this prospect i ve , open-label , single-arm study to receive EPO 60,000 U subcutaneously ( SC ) QW ( initial dosing phase [ IDP ] ) until a target Hb level of 12 g/dl was reached ( maximum 12 weeks ) . Patients who achieved an Hb level of 12 g/dl at any point during the IDP then entered the extended dosing phase ( EDP ; EPO 80,000 U SC Q3W ) . Maximum study duration ( IDP + EDP ) was 24 weeks . The primary endpoint was the proportion of patients achieving a hematopoietic response ( Hb increase ≥ 2 g/dl from baseline or Hb ≥ 12 g/dl ) during the IDP . Results One hundred fifteen patients were enrolled . During the IDP , 76 % ( 84/110 ) of patients achieved a hematopoietic response , and 15 % ( 17/115 ) received red blood cell ( RBC ) transfusion . Sixty-three percent ( 73/115 ) of patients entered the EDP , and 88 % ( 64/73 ) of these patients maintained a mean Hb level > 11.0 and ≤13.0 g/dl . Two of 73 patients received RBC transfusion during the EDP . Adverse events were consistent with the underlying disease and chemotherapy treatment . Conclusion These results suggest that initiation of EPO 60,000 U SC QW is effective in the treatment of CIA and that EPO 80,000 U SC Q3W can be an effective extended dosing option PURPOSE To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin ( R-HUEPO ) compared to " st and ard " treatment ( transfusion for HGB < or = 10.0 g/dL ) improves progression-free survival ( PFS ) , overall survival ( OS ) and local control ( LC ) in women receiving concurrent weekly cisplatin and radiation ( CT/RT ) for carcinoma of the cervix . In addition , to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome . METHODS Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were r and omly assigned to CT/RT+/-R-HUEPO ( 40,000 units s.c . weekly ) . R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS , OS and LC . Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells . RESULTS Between 08/01 and 09/03 , 109 of 114 patients accrued were eligible . Fifty-two received CT/RT and 57 CT/RT+R-HUEPO . The study closed prematurely , with less than 25 % of the planned accrual , due to potential concerns for thromboembolic event ( TE ) with R-HUEPO . Median follow-up was 37 months ( range 9.8 - 50.4 months ) . PFS and OS at 3 years should be 65 % and 75 % for CT/RT and 58 % and 61 % for CT/RT+R-HUEPO , respectively . TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO , not all considered treatment related . No deaths occurred from TE . High-platinum adducts were associated with inferior PFS and LC . CONCLUSION TE is common in cervical cancer patients receiving CT/RT . Difference in TE rate between the two treatments was not statistically significant . The impact of maintaining HGB level > 12.0 g/dL on PFS , OS and LC remains undetermined PURPOSE Patients with primary breast cancer who have extensive axillary lymph node involvement have a poor prognosis after conventional adjuvant therapy . We compared intense dose-dense ( IDD ) adjuvant chemotherapy with conventionally scheduled adjuvant chemotherapy in patients with high-risk primary breast cancer . PATIENTS AND METHODS In this r and omized , phase III trial , a total of 1,284 eligible patients with four or more involved axillary lymph nodes were r and omly assigned to receive IDD sequential epirubicin , paclitaxel , and cyclophosphamide ( IDD-ETC ) every 2 weeks or conventionally scheduled epirubicin/cyclophosphamide followed by paclitaxel every three weeks . The primary end point was event-free survival ( EFS ) . RESULTS At a median follow-up of 62 months , 5-year event-free survival rates were 62 % in the conventional arm and 70 % in the IDD-ETC arm , representing a 28 % reduction of the relative risk of relapse ( P < .001 ) . This benefit was independent of menopausal , hormone receptor , or human epidermal growth factor receptor 2 status . The 5-year overall survival rates were 77 % versus 82 % , representing a 24 % reduction of the relative risk of death ( P = .0285 ) . IDD therapy was associated with significantly more nonhematologic and hematologic toxicities , but no treatment-related death occurred . Four occurrences of acute myeloid leukemia or myelodysplastic syndrome ( MDS ) were observed in the IDD-ETC arm . No severe congestive heart failure was reported . CONCLUSION IDD-ETC was less well tolerated compared with conventional chemotherapy but significantly improved event-free and overall survivals in patients with high-risk primary breast cancer who had four or more positive axillary lymph nodes OBJECTIVE To evaluate the effect of epoetin alfa on quality of life ( QOL ) in patients with solid tumors and mild-to-moderate anemia receiving platinum-based chemotherapy relative to population norms . METHODS In the original study , patients ( n = 316 ) with hemoglobin ( Hb ) levels < or = 12.1 g/dl were r and omized 2:1 to receive either epoetin alfa at a dose of 10,000 U thrice weekly s.c . or best supportive care ( BSC ) to compare the effects on transfusion use , hematologic response , and QOL ( measured by the Functional Assessment of Cancer Therapy-Anemia [ FACT-An ] and Cancer Linear Analogue Scale [ CLAS ] ) . The QOL data from this previously reported trial were reanalyzed here relative to population norms . RESULTS Mean baseline QOL scores were similar between groups . At study completion , mean CLAS , FACT-An , FACT-An Anemia subscale , and FACT-An Fatigue subscale scores were significantly higher for patients given epoetin alfa than for those treated with BSC . Compared with population norms , both groups had impaired QOL at baseline . Differences in mean QOL change scores from baseline to study end for epoetin alfa versus BSC were 3.17 points for the FACT-General Total , 9.90 for the FACT-An Fatigue subscale , and 7.30 for the FACT-An Anemia subscale . This was equivalent to corrections in QOL deficits attributable to epoetin alfa of 97.3 % , 40.7 % , and 38.0 % for the FACT-General Total , FACT-An Fatigue , and FACT-An Anemia subscale scores , respectively , versus BSC . A somewhat greater QOL benefit was observed for the FACT-An Fatigue and FACT-An Anemia subscales in the subset of patients with baseline Hb levels > 10.5 g/dl . CONCLUSION Patients in this study had impaired QOL compared with population norms . Early treatment with epoetin alfa to correct anemia improved QOL in a statistically significant and clinical ly meaningful way , and improvements were greater in patients with baseline Hb levels > 10.5 g/dl Darbepoetin alfa is an erythropoiesis-stimulating agent ( ESA ) approved for treating chemotherapy-induced anemia . This phase II , double-blind , placebo-controlled study examined the efficacy of darbepoetin alfa for treating anemia of cancer ( AoC ) in patients not receiving chemotherapy or radiotherapy . Patients were r and omized 3:1 to receive darbepoetin alfa ( 6.75 microg/kg ) or placebo every 4 weeks ; the end of the study was at week 17 . The primary endpoint was the percentage of patients with a hematopoietic response . Secondary endpoints included transfusion incidence and safety parameters . Efficacy analyses were performed on 162 patients in the darbepoetin alfa group and 56 patients in the placebo group . The Kaplan-Meier percentages of patients who achieved a hematopoietic response ( darbepoetin alfa , 69 % ; placebo , 24 % ) or achieved the target hemoglobin ( darbepoetin alfa , 85 % ; placebo , 50 % ) differed significantly between treatment groups . The transfusion incidence did not differ between treatment groups probably because of the low baseline transfusion rates in AoC patients . The incidence of adverse events ( including on- study deaths ) was similar in both groups . In conclusion , darbepoetin alfa appeared to be well tolerated and significantly increased hemoglobin levels in these AoC study patients Chemotherapy-induced anemia ( CIA ) may substantially impact the health-related quality of life ( HRQoL ) of older cancer patients . This exploratory analysis evaluated the effect of darbepoetin alfa administered as a fixed dose ( 300 microg ) every 3 weeks ( Q3W ) on hematologic outcomes , HRQoL , and safety in older ( > or = 65 years old ) versus younger ( < 65 years old ) patients with CIA ( hemoglobin < 11 g/dl ) . Patients were categorized by age at screening : < 65 , > or = 65 to < 70 , > or = 70 to < 75 , > or = 75 to < 80 , and > or = 80 years old . Patients who received at least one dose of darbepoetin alfa were included in the analysis ; of 1,493 patients , 724 were > or = 65 years old . Age did not appear to influence hematologic outcomes after treatment with darbepoetin alfa ; in all age categories , similar percentages of patients ( 78%-80 % ) achieved the target hemoglobin in approximately the same time ( 4 - 5 weeks ) . Also , the percentage of patients in each age category who received RBC transfusions was reduced from 10%-13 % in month 1 to 2%-4 % in month 4 . Although younger patients reported the greatest improvement in HRQoL scores , approximately one half in each older age category reported clinical ly significant improvement in fatigue , and improvement in the Energy and Overall Health Assessment and Work Productivity and Activity Impairment scales . There were no treatment-related deaths . Treatment-related thromboembolic events were reported by < 1 % of patients < 65 years old and < 1 % of patients > or = 65 to < 70 and > or = 70 to < 75 years old . Darbepoetin alfa Q3W appeared well tolerated and effective for treating older patients with CIA Advanced cancer is frequently associated with a significant anemia that may be due to the disease itself or the effect of concomitantly administered chemotherapeutic agents . In a series of double-blind , placebo-controlled trials , three population s of anemic cancer patients were r and omized to rHuEPO or placebo . The three population s were : A ) patients not receiving concomitant chemotherapy , B ) patients receiving chemotherapeutic regimens which did not contain cisplatin , and C ) patients receiving chemotherapeutic regimens which contained cisplatin . In the no-chemotherapy trials , patients were treated with rHuEPO ( 100 U/kg ) or placebo s.c . three times a week for up to eight weeks . In the two types of chemotherapy trials , patients were treated with rHuEPO ( 150 U/kg ) or placebo SC three times a week for 12 weeks . A total of 413 patients were enrolled in these trials ( 124 in the no-chemotherapy group , 157 in the no-cisplatin chemotherapy group and 132 in the cisplatin chemotherapy group ) . In each trial , patients r and omized to rHuEPO had a significantly greater ( p < .004 ) increase in hematocrit than placebo-treated patients . In the two types of chemotherapy trials combined , utilizing an rHuEPO dose of 150 U/kg , rHuEPO-treated patients had significantly lower ( p < /=.009 ) transfusion requirements ( percentage of patients transfused and mean units of blood transfused per patient ) than placebo-treated patients during months two and three , but not during month one . Quality -of-life parameters measured on a 100 mm visual analog scale significantly improved ( p<.05 ) in rHuEPO-treated patients whose hematocrit increased > /= 6 percentage points , compared to corresponding quality -of-life changes in placebo-treated patients . rHuEPO was well tolerated compared to placebo . The above results suggest that rHuEPO may be a useful agent to palliate the morbid consequences of the anemia that is often found in association with advanced cancer This study evaluated the effects of epoetin alfa on patient-reported outcomes in patients with breast cancer receiving myelotoxic chemotherapy . Early intervention with epoetin alfa was well tolerated and improved anemia-related patient-reported outcomes BACKGROUND This r and omized , open-label study evaluated the efficacy , safety and pharmacokinetics of darbepoetin alfa administered intravenously ( i.v . ) or subcutaneously ( s.c . ) in chemotherapy-induced anemia . PATIENTS AND METHODS Patients received darbepoetin alfa i.v . ( n=59 ) or s.c . ( n=59 ) at a dose of 4.5 mug/kg once weekly for 6 weeks ( correction phase ) followed by 4.5 mug/kg once every 3 weeks for the remainder of the 18-week treatment period ( maintenance phase ) . RESULTS During the correction phase , the mean [ 95 % confidence interval ( CI ) ] change in hemoglobin ( intention-to-treat ) was 1.1 ( 0.6 - 1.5 ) g/dl in the i.v . group and 1.3 ( 0.9 - 1.7 ) g/dl in the s.c . group ; using available data , the mean change was 1.4 ( 1 - 1.9 ) g/dl and 1.6 ( 1.2 - 2 ) g/dl , respectively . The percentage ( 95 % CI ) of patients maintaining hemoglobin ( i.e. average decrease < or = 0.5 g/dl ) during the maintenance phase was similar between the i.v . ( 82 % ; 95 % CI 66 % to 92 % ) and s.c . ( 80 % ; 95 % CI 66 % to 90 % ) groups . Thirty-five per cent ( 95 % CI 20 % to 50 % ) of patients in the i.v . group and 32 % of patients in the s.c . group ( 95 % CI 18 % to 45 % ) received red blood cell transfusions during week 5 to the end of the treatment period . Darbepoetin alfa was well tolerated in both groups . No significant difference ( P=0.36 ) in weekly darbepoetin alfa serum concentrations was observed between groups . CONCLUSIONS Darbepoetin alfa can be administered i.v . or s.c . at equal doses for the treatment of anemia in this setting OBJECTIVE The efficacy and safety of weekly administration of epoetin beta ( EPO ) for chemotherapy-induced anemia ( CIA ) patients was evaluated . METHODS One hundred and twenty-two patients with lung cancer or malignant lymphoma undergoing chemotherapy were r and omized to the EPO 36 000 IU group or the placebo group . Hematological response and red blood cell ( RBC ) transfusion requirement were assessed . Quality of life ( QOL ) was assessed using the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) question naire . RESULTS Mean change in hemoglobin level with EPO increased significantly over placebo ( 1.4 + /- 1.9 g/dl versus -0.8 + /- 1.5 g/dl ; P < 0.001 ) . The proportion of patients with change in hemoglobin level > or = 2.0 g/dl was higher for EPO than those for placebo ( P < 0.001 ) . After 4 weeks of administration , the proportion of RBC transfusion or hemoglobin level < 8.0 g/dl was significantly lower for EPO than those for placebo ( P = 0.046 ) . The changes in the FACT-An total Fatigue Subscale Score ( FSS ) were less deteriorated with EPO than those with placebo . Progressive disease ( PD ) did not influence the change in hemoglobin level but there was less decrease in FSS in non-PD patients . No significant differences in adverse events were observed . Thrombovascular events and pure red cell aplasia related to EPO were not observed . Retrospective analysis of survival showing the hazard ratio of EPO to placebo was 0.94 . CONCLUSION Weekly administration of EPO 36 000 IU significantly increased hemoglobin level and ameliorated the decline of QOL in CIA patients over the 8-week administration period Background : Erythropoietin-stimulating agents ( ESAs ) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia ( CIA ) . Recent studies indicate that ESAs increase mortality and accelerate tumour progression . The studies also identify a 1.6-fold increased risk of venous thromboembolism . The ESA labelling was thus revised in Europe and the United States in 2008 . This is the first r and omised , phase III trial evaluating the efficacy and safety of epoetin-β ( EPO ) , an ESA , dosed in accordance with the revised labelling , which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ⩽10 g dl–1 and that a sustained haemoglobin level of > 12 g dl–1 should be avoided . Methods : A total of 186 CIA patients ( 8.0 g dl–1⩽ haemoglobin ⩽10.0 g dl–1 ) with lung or gynaecological cancer were r and omised to receive EPO 36 000 IU or placebo weekly for 12 weeks . Results : The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl–1 between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group ( n=89 ) than in the placebo group ( n=92 ; 10.0 % vs 56.4 % , P<0.001 ) . The proportion receiving transfusions was significantly lower in the EPO group ( 4.5 % vs 19.6 % , P=0.002 ) . Changes in quality of life were not different . No significant differences in adverse events – for example , the incidence of thromboembolic events was 1.1 % for each group – or the 1-year overall survival were observed between groups . Conclusion : Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment . Further investigations are needed on the effect of ESAs on mortality Introduction Recombinant human erythropoietin ( r-HuEPO ) is used to treat symptomatic anaemia due to chemotherapy . A new r-HuEPO , Epoetin theta ( Eporatio ® ) , was investigated and compared to placebo in a r and omised , double-blind clinical trial in adult cancer patients receiving nonplatinum-based chemotherapy . The primary efficacy endpoint was the responder rate ( complete haemoglobin ( Hb ) response , i.e. , Hb increase ≥2 g/dl ) without the benefit of a transfusion within the previous 4 weeks . Research Design and Methods 186 patients were r and omised to s.c . treatment for 12 weeks with either Epoetin theta ( N = 95 ) or placebo ( N = 91 ) . The starting dose was 20,000 IU once weekly Epoetin theta or placebo . Results The incidence of complete Hb responders was significantly higher in the Epoetin theta group than in the placebo group ( 72.6 vs. 25.3 % , P < 0.0001 ) . More patients in the placebo group than in the Epoetin theta group received blood transfusions after r and omisation ( 23 patients , 25.3 % vs. 13 patients , 13.7 % , P = 0.0277 ) . The majority of patients with a complete Hb response had 20,000 IU/week as their maximum dose prior to response , indicating that a dose of 20,000 IU is an appropriate starting dose . The overall frequencies of adverse events ( AEs ) were similar in both treatment groups . Hypertension was the only AE that was more frequent in the Epoetin theta group compared to the placebo group ( 8.4 vs. 1.1 % ) . Conclusions Epoetin theta showed a superior efficacy to placebo in terms of complete Hb response without blood transfusion within the previous 4 weeks . Treatment with Epoetin theta result ed in a statistically significant increase in mean haemoglobin levels compared to placebo . The overall frequencies of adverse events were similar in both treatment groups In myelodysplastic syndromes ( MDS ) , anemia responds to recombinant human erythropoietin ( rHuEPO ) alone and in combination with recombinant human granulocyte-colony-stimulating factor ( rHuGCSF ) in 10 % to 20 % and in 35 % to 40 % of patients , respectively . We r and omly divided 60 patients with low- grade anemic MDS and serum EPO levels lower than 500 IU/L ( 500 mU/mL ) into 2 groups : rHuEPO + rHuG-CSF ( arm A ) and supportive care ( arm B ) . After 12 weeks , those who had erythroid responses were given rHuEPO alone for 40 additional weeks . They were also given rHuG-CSF if they had relapses . A response was considered major if the hemoglobin ( Hb ) level was 115 g/L ( 11.5 g/dL ) or higher and minor Hb increase was 15 g/L ( 1.5 g/dL ) or more or if it remained stable without transfusion . Ten of 24 patients responded in arm A , and 0 of 26 responded in arm B ( P = .01 ) . Eight patients in arm A continued rHuEPO therapy alone , and 6 had relapses . Responses were always restored when rHuG-CSF was reintroduced . Mean direct costs per patient were 26,723 euros ( arm A ) and 8,746 euros ( arm B ) . Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) scale . Similar percentages of patients from both arms showed significant clinical improvement . rHuEPO plus rHuG-CSF led to responses in 41.7 % of MDS patients . This treatment was expensive . No effect on quality of life was demonstrated Background The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense ( IDD ) sequential chemotherapy with epirubicin ( E ) , paclitaxel ( T ) , and cyclophosphamide ( C ) ( IDD-ETC ) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel ( EC→T ) ( every 3 weeks ) as adjuvant treatment in high-risk breast cancer patients . The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second r and omization of the intense dose-dense arm . Methods One thous and two hundred eighty-four patients were enrolled ; 658 patients were r and omly assigned to the IDD-ETC treatment group . Within the IDD-ETC group , 324 patients were further r and omly assigned to the epoetin alfa group , and 319 were r and omly assigned to the non – erythropoiesis-stimulating agent ( ESA ) control group . Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion . Relapse-free survival , overall survival , and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods . Except for the primary hypothesis , all statistical tests were two-sided . Results Epoetin alfa avoided the decrease in hemoglobin level ( no decrease in the epoetin alfa group vs –2.20g/dL change for the control group ; P < .001 ) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion ( 12.8 % vs 28.1 % ; P < .0001 ) . The incidence of thrombotic events was 7 % in the epoetin alfa arm vs 3 % in the control arm . After a median follow-up of 62 months , epoetin alfa treatment did not affect overall survival , relapse-free survival , or intramammary relapse . Conclusions Epoetin alfa result ed in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival . However , epoetin alfa had an adverse effect , result ing in increased thrombosis BACKGROUND Epoetin ( EPO ) administration reduces the need for transfusion . Identifying patients at high risk of anemia requiring red blood cell ( RBC ) transfusion is needed . This multicentric phase III trial tested epoetin alpha ( EPOalpha ) administration according to our risk model on the basis of three clinical parameters : hemoglobin ( Hb ) < 12 g/dl , lymphocytes < or=700/microl , and /or performance status ( PS ) > 1 . PATIENTS AND METHODS Patients > or=18 years with chemotherapy-treated solid or hematologic tumors were r and omized to 150 UI/kg/TIW s.c . EPOalpha ( arm 1 ) or no EPOalpha ( arm 2 ) and stratified on Hb level at day 0 , lymphocyte count , and PS . The primary end point was transfusion rate ; secondary end points included overall survival ( OS ) , safety , and quality of life . RESULTS From September 2000 to January 2005 , 218 patients ( median age 64 years , 42.7 % males ) with principally breast cancer , sarcoma , or lung carcinoma were included . In total , 93 % patients had PS > 1 and 35 % had < or=700/microl lymphocytes . Baseline Hb levels were 10.1 g/dl ( range 6.9 - 11.9 ) . Two hundred and thirteen patients were assessable for the primary end point : 36 % received RBC in arm 1 and 58 % in arm 2 ( P = 0.0012 ) . Median OS was 7.6 [ 95 % confidence interval ( CI ) : 5 - 12 ] and 6 ( 95 % CI : 5 - 8 ) months in arms 1 and 2 , respectively . Median OS was significantly worse for patients with three prognostic factors ( 3.6 months ) compared with two factors ( 8.3 months ) ( P < 0.001 ) . No difference in toxicity ( 47 % versus 41 % ) or thrombovascular events ( 4.5 % versus 3.7 % ) was observed . CONCLUSION Patients at high risk for RBC transfusion according to the ELYPSE model could be given prophylactic EPO with significantly reduced RBC transfusions and no significant impact on side-effects , progression-free survival , and OS Recent studies have suggested that epoetin treatment of anaemia may influence the survival of patients with cancer . We conducted an analysis of long‐term survival in patients with lymphoproliferative malignancies treated with epoetin‐β or placebo in a large‐scale study . This was a r and omized , double‐blind trial in which patients with transfusion‐dependent anaemia and lymphoproliferative malignancy received epoetin‐β 150 IU/kg or placebo three times weekly for 16 weeks . Long‐term survival data were analysed by st and ard Kaplan – Meier methods and differences between groups were assessed using a log‐rank test . The intention‐to‐treat population consisted of 343 patients ( epoetin‐β , n = 170 ; placebo , n = 173 ) . There were no major differences between the two treatment groups in demographic or clinical characteristics/prognostic factors . A total of 110 ( 65 % ) patients died in the epoetin‐β group ( censored , n = 60 ) and 109 ( 63 % ) died in the placebo group ( censored , n = 64 ) up to the end of long‐term follow up . Kaplan – Meier curves for survival were similar in both groups . Median survival was 17 months with epoetin‐β and 18 months with placebo . A log‐rank test indicated no significant difference in survival ( P = 0·76 ) . This long‐term follow up indicated that epoetin‐β has no significant effect on survival compared to placebo in anaemic patients with lymphoproliferative malignancies Background : Cervical cancer , in women , is the second most common cancer world wide , next to breast cancer . During the treatment of carcinoma cervix , anemia is selectively frequent and its origin is complex combining hemorrhage , iron deprivation , inflammatory reactions and infection . The objective of this study is to evaluate the role of epoetin in correction of anemia and on treatment outcomes in patients with advanced cervical cancer receiving concurrent chemoradiotherapy . Results : A total of 120 patients were enrolled in the study of which 60 patients were r and omized to receive epoetin beta in the treatment arm and 60 patients were in control arm where epoetin beta was not given . Total two and three patients absconded during treatment from treatment and control arm respectively ; therefore total evaluable patients were 115 . Mean Hb at baseline in the control arm was 10.70 + /- 0.62 g/dl and 10.45 + /- 0.43 g/dl in the treatment arm ( p = NS ) . At the end of treatment mean Hb increased by 1.55 g/dl in patients receiving epoetin beta ( p < 0.01 ) , but decreased by 1.50 g/dl in the control arm ( p < 0.01 ) . There was significant reduction in blood transfusion in patients receiving epoetin beta ( p < 0.01 ) . At the end of treatment there was also significant improvement in energy level , activity level and overall quality of life in the treatment arm ( p < 0.01 ) . There was no significant difference in overall survival ( p > 0.05 ) , or disease free survival ( p > 0.05 ) between the two study arms . Adverse events were well matched between the two study arms . No Thromboembolic events associated with epoetin beta was observed in our study . Material and methods : Total 120 , stage IIB to IIIB cervical cancer patients , aged 18 - 70 years with 9.50 - 12.50 g/dl baseline Hb value who were to receive radiotherapy together with cisplatin were r and omized to receive either epoetin beta 10,000 IU thrice weekly and oral iron starting 10 - 15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin ( treatment arm ) or st and ard supportive care ( control arm ) , where epoetin beta was not given . Blood transfusion was given in patients of both the arms if hemoglobin was = 10 g/dl . Conclusions : Treatment with epoetin beta safely and effectively corrects anemia in patients with advanced cervical cancer receiving chemoradiotherapy and is not associated with adverse effects on response rate , overall survival , disease free survival and chemoradiotherapy related acute and late toxicities Summary . This phase 3 , r and omized , double‐blind , placebo‐controlled study was design ed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies . Patients ( n = 344 ) with lymphoma or myeloma received darbepoetin alfa 2·25 μg/kg or placebo s.c . , once weekly for 12 weeks . The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group ( 60 % ) than in the placebo group ( 18 % ) ( P < 0·001 ) , regardless of baseline endogenous erythropoietin level . However , increased responsiveness was observed in patients with lower baseline erythropoietin levels . Darbepoetin alfa also result ed in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase ( 1·80 g/dl vs 0·19 g/dl ) and after 12 weeks of treatment ( 2·66 g/dl vs 0·69 g/dl ) . A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group ( P < 0·001 ) . The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma . Improvements in quality of life were also observed with darbepoetin alfa . The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population . Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy Anemia associated with advanced cancer is common . Contributing factors include the anemia of chronic disease , chemotherapy , radiation therapy , and bone marrow invasion with tumor . Based on the observation that endogenous erythropoietin ( EPO ) levels in anemic patients with cancer are inadequate for the degree of anemia , three r and omized double-blind , placebo-controlled trials of recombinant human erythropoietin ( rHuEPO ) treatment in anemic patients with cancer were performed in patients ( 1 ) not receiving concomitant chemotherapy ( NO CTX ) , ( 2 ) receiving myelosuppressive chemotherapy that did not include cisplatin ( CTX-NO PLAT ) , and ( 3 ) receiving myelosuppressive cisplatin-containing chemotherapy ( CTX-PLAT ) . In the NO CTX trial , patients were treated with rHuEPO 100 U/kg or placebo subcutaneously ( SQ ) three times per week for up to 8 weeks . In the CTX trials , patients were treated with rHuEPO 150 U/kg or placebo SQ three times per week for 12 weeks . Four hundred thirteen patients were enrolled ( 124 , NO CTX ; 157 , CTX-NO PLAT ; and 132 , CTX-PLAT ) . In all three trials , patients receiving rHuEPO had a significantly ( P < .004 ) greater increase in hematocrit ( HCT ) than placebo-treated patients . In the two CTX trials combined , rHuEPO-treated patients also had a significantly ( P < or = .009 ) lower transfusion requirement than placebo-treated patients after the first month of therapy . Quality of life improved significantly ( P < .05 ) in responding ( > or = 6%-point HCT increase without transfusion ) rHuEPO-treated patients compared with placebo-treated patients . Overall , no adverse events occurred more frequently in rHuEPO-treated patients compared with placebo-treated patients . Following completion of the double-blind phase , patients received rHuEPO on an open-label basis as needed for correction of anemia with the dose titrated to a maximum of 900 U/kg/wk . During total rHuEPO exposure ( either started at the beginning of double-blind therapy for patients initially r and omized to rHuEPO or at the beginning of open-label therapy for patients initially r and omized to placebo ; 363 treated/347 evaluable for efficacy ) , 40.0 % , 56.1 % , and 58.3 % of the NO-CTX , CTX-NO PLAT , and CTX-PLAT patients , respectively , responded to rHuEPO therapy with an increase of HCT > or = 6 % unrelated to transfusion . ( ABSTRACT TRUNCATED AT 400 WORDS Impaired cognition , fatigue , and diminished quality of life ( QOL ) are commonly associated with breast cancer chemotherapy . This r and omized , double-blind , placebo-controlled pilot trial assessed the feasibility of quantifying the effects of epoetin alfa on cognitive function and mood , and evaluated its effects on fatigue and QOL in patients with breast cancer treated with anthracycline-based adjuvant or neoadjuvant chemotherapy . Patients were r and omized to receive epoetin alfa 40,000 U subcutaneously once weekly or placebo at the beginning of 4 cycles of chemotherapy administered over 12 weeks . Cognitive function was assessed by Executive Interview ( EXIT25 ) and Clock Drawing Tasks ; mood by Profile of Mood States ; anemia-related symptoms , including fatigue , by the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) subscale ; and QOL by Linear Analog Scale Assessment . Ninety-four patients were evaluable for efficacy and safety . Mean change in EXIT25 scores from baseline to cycle 4 in the epoetin alfa group was 1.3 + /- 3.3 ; the mean change was 0.3 + /- 2.4 in the placebo group ( a negative change indicates improved executive function ) . There was no difference between groups in mean change in EXIT25 score from baseline to 6-month follow-up assessment . Mean hemoglobin levels were higher in the epoetin alfa group compared with the placebo group after 4 cycles of chemotherapy . Epoetin alfa recipients had less of a decrease in FACT-An subscale scores from baseline to cycle 4 and improvement in FACT-An subscale scores at 6-month follow-up assessment compared with placebo . Epoetin alfa therapy was well tolerated . These data suggest that epoetin alfa may have attenuated the cognitive impairment and fatigue that occurred during adjuvant breast cancer chemotherapy 513 Background : Dose-dense chemotherapy will become a new treatment option in breast cancer patients ( pts ) ( INT C9741 ) . Here we report the initial results of a second prospect i ve r and omized trial that compares dose-dense vs. conventionally scheduled sequential chemotherapy in high-risk node positive pts . METHODS A multi-center phase-III trial of the German " Arbeitsgemeinschaft fuer Gynaekologische Onkologie ( AGO ) " recruited 1284 pts from 12/98 until 4/03 . Pts below 65 years of age were eligible if they had at least 4 involved axillary lymph nodes . In the experimental arm , pts were assigned to receive three courses each of epirubicin(150 mg/m2 ) , paclitaxel ( 225 mg/m2 ) and cyclophosphamide ( 2500 mg/m2 ) at 2 weeks interval ( q2wks ) ( ETC ) with G-CSF support ( 5μg/kg/SC day 3 - 10 ) . A second r and omization ± Epoetin-alpha was performed ( 150 IU/kg/SC three times weekly ) . In the st and ard arm 4 courses of conventional dosed epirubicin/cyclophosphamide ( 90/600 mg/m2 ) followed by 4 courses of paclitaxel ( 175 mg/m2 ) ( q3wks ) were given . RESULTS Median patient age was 50 years . Risk factors were well balanced in both arms . 59 % and 41 % of the pts had 4 - 9 and ≥10 infiltrated nodes . The median number of positive nodes was 8 . In this second interim analysis 1169 pts were fully evaluable . No unusual toxicities were seen , especially no severe cardiotoxicity . Hematological toxicity ( anemia , neutropenia and thrombopenia ) was more frequent in the ETC arm ( p<0,0001 ) and varied distinctly between drugs . The incidence was highest during treatment with cyclophosphamide and lowest during treatment with paclitaxel . 7 % of pts in the ETC arm vs. 2 % in the st and ard arm were hospitalized for febrile neutropenia ( p<0,0001 ) . There were no treatment-related deaths during therapy . 82 % of pts in the ETC arm vs. 90 % in the st and ard arm received the planned number of cycles . The number of dose reductions was relatively small , ranging from 6,5 % on the ETC arm to 2 % on the st and ard arm . At a median follow-up of 28 months 94 pts in the ETC arm vs. 127 pts in the st and ard arm had relapsed . This difference was highly significant in the two-sided log-rank test ( p=0,0009 ) with a HR of 0,64 ( 95 % CI : 0,49 - 0,83 ) . Estimated 3-year RFS is 80 % in the ETC arm vs. 70 % in the st and ard arm . 103 pts have died ( 43 events vs. 60 events ) favoring again the ETC arm ( two-sided log-rank test : p=0,030 ; HR : 0,65 ( 95 % CI : 0,44 - 0,96 ) . Estimated 3-year OAS is 90 % in the ETC arm vs. 87 % in the st and ard arm . There was a highly significant difference in anemia grade 1 - 4 as well as in the number of RBC 's transfusions between ETC ± Epoetin alpha ( p<0,0001 ) . No difference in DFS ( p=0,84 ) or OAS ( p=0,98 ) was found between ETC ± Epoetin alpha . CONCLUSIONS Evidence to date indicates that the dose-dense ETC-regimen as adjuvant therapy in high-risk breast cancer pts is well tolerated and significantly improves DFS and OAS . Confirming the results of INT C9741 , dose-dense sequential regimens may become a future st and ard option in the adjuvant treatment of node positive breast cancer pts . [ Table : see text ] The development and validation of a short and simple measure of perceived health problems is described . Extensive testing with selected groups , including the elderly , the chronically ill , pregnant women , fracture victims , and a r and om sample of the community has established the face , content and criterion validity , and the reliability of the instrument . The Nottingham Health Profile is intended as a st and ardized tool for the survey of health problems in a population , but is equally valid and useful as a means of evaluating the outcome of medical and /or social interventions and as an adjunct to the clinical interview PURPOSE Although erythropoietin ( EPO ) is known to be useful in treating chemotherapy-induced anemia , few data are available on its potential preventive role . The aim of this study was to evaluate the ability of EPO in preventing the development of clinical ly significant anemia in patients treated with chemotherapy . PATIENTS AND METHODS Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were r and omized to receive EPO 150 U/kg three times a week or no additional treatment . Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2 , epirubicin 60 mg/m2 , and fluorouracil 600 mg/m2 ( CEF ) intravenously on day 1 , every 2 weeks with the support of granulocyte colony-stimulating factor ( G-CSF ) , 5 microg/kg subcutaneously from day 4 to day 11 . RESULTS Throughout the six cycles of chemotherapy , EPO-treated patients maintained stable values of hemoglobin , whereas control patients developed a progressive anemia . At the end of chemotherapy , the mean ( + /- SD ) hemoglobin decrease in the control group was 3.05 g/dL ( + /- 1.0 ; 95 % confidence interval [ CI ] , 2.6 to 3.5 ) , whereas in the EPO group it was 0.8 ( + /- 1.4 ; 95 % CI , 0.3 to 1.4 ) . Clinical ly significant anemia ( hemoglobin < or = 10 g/dL ) occurred in 16 patients ( 52 % ; 95 % CI , 33 to 69 ) in the control arm and in no patient ( 0 % ; 95 % CI , 0 to 14 ) in the EPO arm ( P = .00001 ) . CONCLUSION EPO prevents anemia in patients undergoing chemotherapy . Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective BACKGROUND Anaemia is associated with poor cancer control , particularly in patients undergoing radiotherapy . We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer . METHODS We did a multicentre , double-blind , r and omised , placebo-controlled trial in 351 patients ( haemoglobin < 120 g/L in women or < 130 g/L in men ) with carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx . Patients received curative radiotherapy at 60 Gy for completely ( R0 ) and histologically incomplete ( R1 ) resected disease , or 70 Gy for macroscopically incompletely resected ( R2 ) advanced disease ( T3 , T4 , or nodal involvement ) or for primary definitive treatment . All patients were assigned to subcutaneous placebo ( n=171 ) or epoetin beta 300 IU/kg ( n=180 ) three times weekly , from 10 - 14 days before and continuing throughout radiotherapy . The primary endpoint was locoregional progression-free survival . We assessed also time to locoregional progression and survival . Analysis was by intention to treat . FINDINGS 148 ( 82 % ) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L ( women ) or 150 g/L ( men ) compared with 26 ( 15 % ) given placebo . However , locoregional progression-free survival was poorer with epoetin beta than with placebo ( adjusted relative risk 1.62 [ 95 % CI 1.22 - 2.14 ] ; p=0.0008 ) . For locoregional progression the relative risk was 1.69 ( 1.16 - 2.47 , p=0.007 ) and for survival was 1.39 ( 1.05 - 1.84 , p=0.02 ) . INTERPRETATION Epoetin beta corrects anaemia but does not improve cancer control or survival . Disease control might even be impaired . Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials 9048 Background : Use of erythropoiesis-stimulating agents ( ESAs ) in chemotherapy-induced anemia is a major issue . Based on recent studies , FDA has modified labeling for ESAs to include a black box warning that limited prescription to pts receiving chemotherapy for non-curative intent . The GELA has conducted a r and omized phase III study to evaluate survival impact of Darbepoetin alfa ( DA ) in pts with DLBCL treated by chemotherapy . We report results of the second interim analysis , with a median follow-up of 44 months Methods : Pts aged from 60 to 80y with DLBCL and aaIPI≥1 were eligible and r and omized between two chemotherapy regimens ( R-CHOP14 or R-CHOP21 ) for 8 cycles and between an investigational arm with DA given to maintain Hb level between 13 and 15 g/dL and a conventional arm with usual management of anemia , including transfusion and ESA . Objective was to evaluate efficacy of DA as measured by PFS , EFS , DFS and OS , and to analyze toxicity Results : 602 pts were included , 600 were evaluable ; 238 in DA arm and 362 in conventional arm , difference being a consequence of transient stop of r and omization asked by French Authorities in 2005 . Median age was 70 years . Pts characteristics were similar in both arms . Median baseline Hb level was 12.3 g/dL. During treatment , median Hb level was 11.6 g/dL in DA arm and 10.8 g/dL in conventional arm . Response rate was similar in both arms . Three-year PFS was 66 % in DA arm compared to 58 % in conventional arm ( HR 0.77 ; CI95 % : 0.59 - 0.99 ; p=0.04 ) . This difference was also significant for DFS ( HR 0.65 ; CI95 % : 0.45 - 0.92 ; p=0.02 ) . Despite a trend , OS was not statistically significantly longer in DA arm ( HR 0.81 ; CI95 % : 0.60 - 1.09 ; p=0.16 ) . In conventional arm , 40 % of pts received ESA . Despite no difference in Hb level , PFS was better when comparing pts who receive ESAs with those who did not ( HR : 0.73 ; CI95 % : 0.57 - 0.94 ; p=0.01 ) . Rate of thrombotic events was higher in DA arm ( 13 % ) than in conventional arm ( 6 % ) . Number of serious adverse events and treatment-related deaths were similar in both arms . CONCLUSIONS Prophylactic use of DA was associated with better PFS . This is the first evidence of positive survival impact of DA in pts receiving chemotherapy for malignancy Summary . Darbepoetin alfa is a novel erythropoiesis‐stimulating protein with a prolonged serum half‐life . This r and omized , double‐blind , placebo‐controlled , dose‐finding study investigated the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies who were receiving chemotherapy . Patients were r and omized in a 1:2:2:1 ratio to receive darbepoetin alfa 1·0 μg/kg ( n = 11 ) , 2·25 μg/kg ( n = 22 ) , 4·5 μg/kg ( n = 22 ) or placebo ( n = 11 ) , administered subcutaneously once weekly for 12 weeks . No dose increases were allowed during the study . A higher proportion of patients achieved a haemoglobin response ( defined as a ≥ 2·0 g/dl increase from baseline ) in the darbepoetin alfa 1·0 μg/kg ( 45 % ) , 2·25 μg/kg ( 55 % ) and 4·5 μg/kg ( 62 % ) groups than in the placebo group ( 10 % ; P < 0·01 ) . The mean change in haemoglobin from baseline to week 13 was 1·56 g/dl in the 1·0 μg/kg group , 1·64 g/dl in the 2·25 μg/kg group and 2·46 g/dl in the 4·5 μg/kg group , compared with a mean change of 1·00 g/dl in the placebo group . The overall safety profile of darbepoetin alfa in this study was similar to that of placebo . These results show that darbepoetin alfa effectively and safely increased haemoglobin concentrations in patients with lymphoproliferative malignancies . Confirmative studies at doses of 2·25 and /or 4·5 μg/kg/week in this population are warranted Abstract Objective : Cancer-related anaemia is associated with fatigue that adversely affects patients ’ everyday functioning and wellbeing . We explore the impact of fatigue on patient productivity and caregiver burden . Methods : The analyses are based on data from a r and omised , open-label , active-controlled , dose-finding trial of darbepoetin alfa among solid-tumour cancer patients with anaemia , who are receiving chemotherapy . Fatigue is assessed with the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale score . Productivity and caregiver outcomes include time ( hours ) missed from usual activities , amount of assistance ( hours ) needed from others , overall ability to perform desired activities and ability to perform family responsibilities . These outcomes are assessed at baseline and the end of the 12-week treatment period . ANOVA and linear regression models are used to evaluate associations . Results : Patients ( n = 300 ) were aged 61 years on average , with a mean ( SD ) baseline haemoglobin of 9.9 ( 0.9 ) g/dL. FACT-Fatigue subscale score improvements were significantly ( p = 0.003 ) associated with haemoglobin improvements . Over a 2-week period , after controlling for age , sex and disease progression , one-point improvements in FACT-Fatigue subscale scores corresponded to a 1-hour ( 95 % CI 0.5 , 1.5 ) gain in productive time , 0.7-hour ( 95 % CI 0.4 , 1.0 ) reduction in caregiver time and 1.6 % ( 95 % CI 1.4 , 1.7 ) improvement in overall activity . Conclusions : Reducing fatigue is associated with gains in productive time , reductions in caregiver burden and enhanced ability to perform activities . These outcomes may have broader implication s for patients ’ wellbeing and for the societal impact of cancer-related fatigue and anaemia Patients with cancer who are receiving chemotherapy often experience chemotherapy‐induced anemia ( CIA ) , which is associated with symptoms that reduce quality of life . The M. D. And erson Symptom Inventory ( MDASI ) is a brief , self‐rating assessment scale that measures the severity of core symptoms and symptom interference with function . The current study used the MDASI to prospect ively assess the correlation between hemoglobin and self‐perceived cancer‐related symptoms in a large patient population with CIA who were receiving darbepoetin‐α at a dose of 200 μg every 2 weeks Recombinant human erythropoietin ( rHu-EPO ) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions , including bone marrow tumors such as multiple myeloma ( MM ) . We studied a group of 54 patients with MM undergoing second-induction chemotherapy . Thirty of them were r and omly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week , increased to 300 units/kg from the sixth week to the end of the 24-week study . Hemoglobin ( Hb ) levels increased in 77.7 % of these patients by the eighth week . In addition , five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month , whereas seven control patients required frequent supplements . Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts , whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy . The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocol s combined with α-interferon ( α-IFN ) included an increase of serum IgM after the third month . This effect was not demonstrable in any other group , including three rHu-EPO-untreated patients undergoing α-IFN + VMCP combined therapy , as well as rHu-EPO-treated patients not receiving a-IFN . Our data suggest that α-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function . These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro PURPOSE Patients with ovarian cancer often experience dose-limiting myelotoxicity , nephrotoxicity and anemia following treatment with platinum-based chemotherapy . PATIENTS AND METHODS To investigate the ability of recombinant human erythropoietin ( epoetin alfa ) to prevent the development of anemia , 30 patients with advanced ovarian carcinoma receiving cisplatin or carboplatin were r and omly assigned to treatment with subcutaneous epoetin alfa 300 IU/kg three times a week in addition to conventional supportive treatment , or conventional supportive treatment alone , for up to six chemotherapy cycles . The dose of epoetin alfa was reduced if hemoglobin concentration exceeded 15 g/dL. RESULTS A highly significant difference in mean hemoglobin concentrations was observed between the two groups during the first cycle of chemotherapy due to a significant decrease in mean hemoglobin concentration in the control group . A maximal difference of 3.4 g/dL was achieved during cycle three . Fewer patients required blood or platelet transfusions in the epoetin alfa-treated group , although the difference was not significant compared to the control group . Epoetin alfa was well tolerated . CONCLUSION Epoetin alfa appears to be effective and well tolerated in preventing hemoglobin decline in patients undergoing aggressive cyclic platinum-based chemotherapy for advanced ovarian carcinoma This r and omized , controlled trial evaluated the effect of darbepoetin alfa on hospitalization days , transfusion requirements , hemoglobin levels , and fatigue in patients with anemia of cancer ( AOC ) . Eligible patients were anemic ( hemoglobin < or=11 g/dl ) due to cancer , > or=18 years old , and had not received chemotherapy or radiotherapy within 4 weeks of study screening . Patients were r and omized 4:1 to receive darbepoetin alfa , 3.0 microg/kg every 2 weeks ( Q2W ) ( n = 226 ) , or observation only for 12 weeks ( n = 59 ) , followed by an optional 9 weeks of darbepoetin alfa , 3.0 microg/kg Q2W . Endpoints were compared between the two treatment arms at week 13 . A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect , so the study was terminated early . Therefore , results for the primary endpoint should be interpreted cautiously . The hospitalization rate was similar ( 0.5 days ) for both the darbepoetin alfa and observation groups ( p = .73 ) . Transfusion incidence ( weeks 5 - 12 ) was significantly lower for darbepoetin alfa patients ( 8 % ) than for observation patients ( 22 % ) ( p = .0092 ) . By week 13 , hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa , compared with 0.1 g/dl in the observation group p < .0001 . Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy-Fatigue score ( mean change in score at week 13 : darbepoetin alfa , 6.0 ; observation , 2.2 ; p < .05 ) . Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC , result ing in significant improvements in health-related quality of life PURPOSE To compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia . PATIENTS AND METHODS Eligible patients were r and omly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously ( SC ) , followed by either st and ard weekly epoetin alfa ( 40 K arm ) or 120,000 U of epoetin alfa ( 120 K arm ) SC every 3 weeks for 18 additional weeks . RESULTS Three hundred sixty-five patients were enrolled . One hundred eighty-three patients were assigned to the 40 K arm , and 182 were assigned to the 120 K arm . There was no difference in the proportion of patients requiring transfusions during the study ( 23 % in 40 K arm and 18 % in 120 K arm , P = .22 ) or specifically during the maintenance phase ( 13 % in 40 K arm v 15 % in 120 K arm , P = .58 ) . Patients r and omly assigned to the 40 K arm were more likely to have a > or = 2 or > or = 3 g/dL hemoglobin ( Hb ) increment , were more likely to have a drug dose held because of high Hb , and had higher mean end-of- study Hb levels . Toxicities , including thromboembolism , and overall survival were similar . Patients in the 40 K arm had a higher global quality of life ( QOL ) at baseline for unclear reasons , whereas patients in the 120 K arm had a greater global QOL improvement during the study , so end-of- study QOL was equivalent . CONCLUSION After three weekly doses of epoetin alfa 40,000 U , a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL . The Hb increment is somewhat greater with continued weekly epoetin alfa . Lack of blinding as a result of different treatment schedules may have confounded results BACKGROUND Patients receiving chemotherapy often develop anemia . Darbepoetin alfa ( Aranesp(TM ) ) is an erythropoiesis-stimulating glycoprotein that has been shown , in dose-finding studies , to be safe and clinical ly active when administered to patients with cancer every 1 , 2 , or 3 weeks . This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy . METHODS In this multicenter , double-blind , placebo-controlled study , 320 anemic patients ( hemoglobin < or=11.0 g/dL ) were r and omly assigned to receive darbepoetin alfa or placebo injections weekly for 12 weeks . The 297 patients who completed at least the first 28 days of study were assessed for red blood cell transfusions , the primary endpoint . Patients were also assessed for hemoglobin concentration ( i.e. , hematopoietic response ) , adverse events , antibody formation to darbepoetin alfa , hospitalizations , Functional Assessment of Cancer Therapy (FACT)-Fatigue score , and disease outcome . Efficacy endpoints were assessed using Kaplan-Meier analyses , Cox proportional hazards analyses , and chi-square tests where appropriate . All statistical tests were two-sided . RESULTS Patients receiving darbepoetin alfa required fewer transfusions ( 27 % versus 52 % ; mean difference = 25 % ; 95 % confidence interval [ CI ] = 14 % to 36 % ; P<.001 ) , required fewer units of blood ( 0.67 versus 1.92 ; mean difference = 1.25 , 95 % CI = 0.65 to 1.84 ; P<.001 ) , had more hematopoietic responses ( 66 % versus 24 % ; mean difference = 42 % ; 95 % CI = 31 % to 53 % ; P<.001 ) , and had better improvement in FACT-Fatigue scores ( 56 % versus 44 % overall improvement ; 32 % versus 19 % with > or=25 % improvement ; mean difference = 13 % ; 95 % CI = 2 % to 23 % , P = .019 ) than patients receiving placebo . Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug . Adverse events were similar between the groups . CONCLUSIONS Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy . Darbepoetin alfa decreased blood transfusion requirements , increased hemoglobin concentration , and decreased fatigue . Although no conclusions can be drawn about survival from this study , the potential salutary effect on disease outcome warrants further investigation in a prospect ively design ed study Goals Currently , there is some debate concerning the haemoglobin level at which treatment of anaemia with erythropoiesis-stimulating agents should be initiated in cancer patients on chemotherapy . We report several analyses of data from a phase III trial of darbepoetin alfa versus placebo , comparing outcomes for patients with mild and moderate-to-severe anaemia . Patients and methods Data were obtained from a phase III trial of darbepoetin alfa versus placebo in anaemic patients with lung cancer receiving chemotherapy ( n=314 ) . Outcomes were compared for patients with baseline haemoglobin ≥10–11 g/dl and < 10 g/dl . Results Darbepoetin alfa significantly reduced transfusions compared with placebo , irrespective of haemoglobin level at treatment initiation . For patients with baseline haemoglobin < 10 g/dl , 31 % and 59 % of those receiving darbepoetin alfa and placebo , respectively , required a transfusion from week 5 to the end of the treatment phase ( P<0.038 ) . For patients with baseline haemoglobin ≥10 g/dl , the proportions were 15 % and 41 % , respectively ( P<0.001 ) . Darbepoetin alfa also improved fatigue compared with placebo in both haemoglobin categories . Conclusions These findings show that initiating treatment at haemoglobin levels both < 10 g/dl and ≥10–11 g/dl results in substantial clinical benefits , supporting the use of erythropoietic therapy also in patients with mild anaemia Darbepoetin alfa ( DA ) is an erythropoiesis-stimulating agent ( ESA ) approved for treating chemotherapy-induced anemia ( CIA ) . Safety concerns have prompted changes to the ESA-product information , which now recommends initiating ESAs at hemoglobin ( Hb ) levels < 10 g/dL ( US ) or ≤10 g/dL ( EU ) . The present exploratory analysis of a DA trial examined how baseline-Hb levels at ESA initiation affect transfusion rates , Hb response , and safety outcomes in CIA patients . Data were retrospectively analyzed from a phase 3 trial of CIA patients r and omised to 500 mcg DA every 3 weeks ( Q3 W ) or to 2.25 mcg/kg DA weekly ( QW ) for 15 weeks . In the current analysis , data were reanalyzed by baseline-Hb categories of < 9 g/dL ( n = 126 ) , 9 to < 10 g/dL ( n = 225 ) , and ≥10 g/dL ( n = 354 ) . The Q3 W and QW groups were combined . Transfusion rates were highest in the < 9 g/dL baseline-Hb group in all time periods examined . The Kaplan – Meier percentage ( 95 % CI ) of patients achieving Hb ≥10 g/dL was 68 % ( 59 , 78 ) and 88 % ( 82 , 92 ) in the < 9 g/dL and 9 to < 10 g/dL baseline-Hb groups , respectively . With lower baseline-Hb , incidence of a ≥1 g/dL-Hb rise in 14 days progressively decreased . Incidence of venous thromboembolic events was similar in all baseline-Hb groups and similar between patients with or without a ≥1 g/dL-Hb rise in 14 days . Overall , transfusion risk increased and Hb response decreased at lower baseline-Hb levels in this exploratory analysis . When following ESA-product information to initiate ESAs at Hb ≤ 10 g/dL , the greatest benefit may be achieved when initiating close to 10 g/dL. Prospect i ve studies are needed to further examine this hypothesis PURPOSE This r and omized , double-blind , placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements , hematopoietic parameters , quality of life ( QOL ) , and safety in anemic cancer patients receiving nonplatinum chemotherapy . The study also explored a possible relationship between increased hemoglobin and survival . PATIENTS AND METHODS Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL , or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy , were r and omized 2:1 to epoetin alfa 150 to 300 IU/kg ( n = 251 ) or placebo ( n = 124 ) three times per week subcutaneously for 12 to 24 weeks . The primary end point was proportion of patients transfused ; secondary end points were change in hemoglobin and QOL . The protocol was amended before unblinding to prospect ively collect and assess survival data 12 months after the last patient completed the study . RESULTS Epoetin alfa , compared with placebo , significantly decreased transfusion requirements ( P = .0057 ) and increased hemoglobin ( P < .001 ) . Improvement of all primary cancer- and anemia-specific QOL domains , including energy level , ability to do daily activities , and fatigue , was significantly ( P < .01 ) greater for epoetin alfa versus placebo patients . Although the study was not powered for survival as an end point , Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa ( P = .13 , log-rank test ) , and Cox regression analysis showed an estimated hazards ratio of 1.309 ( P = .052 ) favoring epoetin alfa . Adverse events were comparable between groups . CONCLUSION Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy . Encouraging results regarding increased survival warrant another trial design ed to confirm these findings PURPOSE To evaluate the effect of exogenous recombinant human erythropoietin ( rHuEPO ) on the increase of hemoglobin levels and on the transfusion requirements in patients with cisplatin (CDDP)-induced anemia , we performed a double-blind r and omized trial with placebo . PATIENTS AND METHODS One hundred patients with CDDP-associated anemia ( hemoglobin level < 90 g/L ) were r and omized to receive either placebo ( saline solution ) or rHuEPO ( 100 U/kg body weight subcutaneously ) three times per week . The end points of this study were the increase in hemoglobin levels to greater than 100 g/L after 3 , 6 , and 9 weeks and the effect on transfusion requirements . RESULTS Ninety-nine of 100 patients were assessable for response and toxicity . In the rHuEPO arm , mean hemoglobin levels were statistically significantly increased after the third , sixth , and ninth weeks of therapy ( 101.1 + /- 9.0 , 102.4 + /- 6.6 , and 105.1 + /- 9.4 g/L , respectively ) compared with the mean baseline value ( 86.3 + /- 6.2 g/L ) . In the placebo arm , there were no increases in mean hemoglobin levels at the third , sixth , and ninth weeks ( 81.0 + /- 5.2 , 81.3 + /- 9.2 , and 81.2 + /- 11 g/L , respectively ) compared with the mean baseline value ( 87.3 + /- 5.2 g/L ) . Furthermore only 20 % of patients required blood transfusions in the rHuEPO arm versus 56 % of patients in the placebo arm ( P = .01 ) , with a mean units of blood transfused per patient of 0.30 in the rHuEPO arm and 1.8 in the placebo arm ( P = .01 ) . Treatment was well tolerated , with no significant side effects . CONCLUSION CDDP-induced anemia is corrected by rHuEPO , which results in reduced blood transfusion requirements The introduction of longer-acting erythropoietic agents into the practice of oncology has dem and ed an underst and ing of the interaction of chemotherapy with the pharmacokinetics and haematological effects of these erythropoietins . We report results of a r and omised trial comparing the haematological effects of darbepoetin alfa , 6.75 mug/kg , administered once every 3 weeks to anaemic cancer chemotherapy patients on either an asynchronous ( day 15 ) or synchronous ( day 1 ) schedule relative to their every-3-week chemotherapy . A total of 81 patients were r and omised and received the study drug ( 43 asynchronous ; 38 synchronous ) . No difference was observed between groups in the primary endpoint of mean haemoglobin change after 6 weeks of therapy ( P=0.45 ) and change scores were similar to those observed with st and ard weekly darbepoetin alfa therapy . In a subset of patients evaluated with intensive pharmacokinetic sampling , an increase in endogenous erythropoietin concentration ( up to 4-fold ) lasting approximately 1 week following chemotherapy administration was observed in both groups . Synchronous administration of darbepoetin alfa was associated with a 1.3-fold increase in the area under the darbepoetin alfa concentration-time curve compared with asynchronous administration . Our data suggest that darbepoetin alfa is effective administered every 3 weeks regardless of timing of administration with respect to chemotherapy and that receptor-mediated uptake by the erythron may be an important clearance mechanism for erythropoietic proteins Background and objective : To report the design , methodology , implementation and initial results of the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies ( DOSE ) Registry , the first US patient registry to collect and report on practice patterns and outcomes associated with erythropoiesis-stimulating therapy ( EST ) for anaemia management in oncology patients . Methods : DOSE is a prospect i ve ongoing registry of oncology patients treated with epoetin-α or darbepoetin-α . Patients from either community or academic centres who meet prespecified entry criteria are eligible for inclusion in the registry . Data collected include patient demographic and clinical characteristics , EST administration , haematological parameters , patient-reported outcomes and medical re source utilization . Patients are followed from EST initiation through to the end of therapy or 16 weeks , whichever is earlier . Results : Initial results from 45 sites for 861 patients ( epoetin-α , n = 312 ; darbepoetin-α , n = 549 ) showed that baseline demographic and disease characteristics were similar between the two treatment groups . Administration of EST at both weekly and ≥2-weekly intervals was observed in both groups , with similar numbers of haemoglobin determinations . However , the mean number of office visits was higher in the darbepoetin-α group despite more frequent administration of therapy at ≥2-weekly intervals in this group . Mean treatment duration was approximately 8 weeks for both groups . Mean post-baseline haemoglobin levels of 11–12 g/dL were achieved and maintained at all timepoints assessed with epoetin-a but not with darbepoetin-α . Both groups had similar rates of packed red blood cell transfusions . Conclusions : The DOSE Registry is a valuable source of data relating to anaemia management , practice patterns and outcomes in oncology patients from the perspective of actual clinical practice . Results from this registry should provide patients , clinicians and healthcare decision makers with a better underst and ing of the relationship between EST dosage and outcomes in the clinical setting Abstract Background . We studied the clinical effect of recombinant human erythropoietin ( r-huEPO ) on anemia induced by two courses of cisplatin-based chemotherapy in patients with non-small cell lung cancer ( NSCLC ) . Methods . Seventy-two patients with NSCLC were r and omized into three groups , receiving 100 , or 200 IU/kg of r-huEPO , or placebo . The r-huEPO and placebo were administered subcutaneously three times a week for 6 weeks , starting 2 weeks after the initiation of chemotherapy . Results . In the 53 evaluable patients , hemoglobin ( Hb ) levels at the nadir after the second cycle of chemotherapy were significantly elevated compared with the nadir after the first cycle in both r-huEPO treated groups , while this level was decreased in the placebo group . Hb levels at the end of the second course of chemotherapy ( week 8) in both r-huEPO groups were higher than that in the placebo groups . No adverse drug reaction attributable to r-huEPO was observed . Serum erythropoietin levels after the administration of r-huEPO were higher than those after placebo administration . Conclusions . r-huEPO had an effect in preventing anemia in patients with NSCLC who had cisplatin-based chemotherapy PURPOSE A placebo-controlled , double-blind , r and omized , phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival . PATIENTS AND METHODS Darbepoetin alpha ( 300 microg ) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy ( carboplatin plus etoposide or cisplatin plus etoposide ) plus 3 weeks after the last dose of chemotherapy . Patients with disease progression were observed until death or until all patients completed their end-of- study visit and 496 deaths had occurred . The two co primary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival ; statistical testing of survival was done if change in hemoglobin was significant at P < .05 . RESULTS The study enrolled 600 patients . Patients ' hemoglobin levels dropped due to the myelosuppressive chemotherapy ; however , treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo ( P < .001 ) . There was no statistically significant difference in overall survival between the treatment groups ( hazard ratio [ HR ] , 0.93 ; 95 % CI , 0.78 to 1.11 ; P = .431 ) . As expected , darbepoetin alpha was associated with a higher incidence of thromboembolic events ( darbepoetin alpha , 9 % ; placebo , 5 % ) . The transfusion risk was lower in the darbepoetin versus placebo group ( HR , 0.40 ; 95 % CI , 0.29 to 0.55 ) . CONCLUSION The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha ; however , they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia Anemia has been reported to develop during preoperative chemotherapy with paclitaxel and carboplatin . The use of recombinant human erythropoietin ( EPO ) has been shown to reduce anemia and subsequent packed red blood cell transfusions . The current study is a report of a Phase III , prospect i ve , r and omized trial with or without EPO that confirms the original observations of less anemia and fewer transfusions in those patients r and omized to receive EPO concurrently with paclitaxel and carboplatin ABSTRACT Objective : Darbepoetin alfa is effective in treating chemotherapy-induced anemia ( CIA ) . Administration of subcutaneous darbepoetin alfa every 3 weeks ( Q3W ) could simplify treatment through synchronization with common Q3W chemotherapy regimens . We report results from a multicenter , r and omized , double-blind , placebo-controlled , phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA . Research design and methods : Patients aged ≥ 18 years with anemia ( hemoglobin < 11 g/dL ) being treated for nonmyeloid malignancy were r and omized 1:1 to receive darbepoetin alfa 300 μg ( n = 193 ) or placebo ( n = 193 ) subcutaneously Q3W from weeks 1 to 13 in this 16-week study . Doses could be adjusted per prespecified rules . Main outcome measures : The primary endpoint was the proportion of patients who received ≥1 red blood cell ( RBC ) transfusion between week 5 and the end of the treatment period ( EOTP ) . The study also analyzed the proportions of patients achieving a hemoglobin concentration ≥11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL , and the change in hemoglobin concentration over time . Results : The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group ( 24 vs. 41 % of patients , a 16.3 % difference , p < 0.001 ) . There were no differences between the two treatment arms in quality -of-life measures . Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels . Study limitations suggest caution in the interpretation of these results : transfusions , the primary endpoint , were recommended but not required if hemoglobin concentrations were ≤8.0 g/dL , and protocol deviations ( primarily dosing errors ) occurred in approximately one-half of the patients in both treatment groups . Conclusions : In this study , fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA . Trial registration : Clinical Trials.gov identifier : NCT00110955 PURPOSE To determine whether the addition of recombinant human erythropoietin ( Epo ) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS AND MATERIAL S Eligible patients had SCCHN , with a plan for continuous-course definitive radiotherapy ( 66 - 72 Gy ) with or without chemotherapy . Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and /or accelerated fractionation radiotherapy . Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL ( 12.5 g/dL for women ) . Patients r and omized to Epo received 40,000 U once weekly , starting 7 - 10 days before start of radiotherapy . RESULTS A total of 148 patients were enrolled ; 141 were evaluable . Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm , compared with an average 0.24 g/dL decrease in the control arm ( p = 0.0001 ) . Median follow-up was 2.5 years ( 3.1 years for surviving patients ) . There was no statistically significant difference in the primary endpoint of local-regional failure ( LRF ) rate between the treatment arms . The 3-year LRF rate was 36 % for control and 44 % for Epo ( p = 0.56 ) . There were also no significant differences in local-regional progression-free survival ( LRPFS ) , patterns of failure , overall survival , or toxicity . The 3-year LRPFS rate was 52 % for control and 47 % for Epo . The overall survival rate was 57 % and 56 % , respectively . CONCLUSIONS The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes . The study was not specifically design ed to detect a potential negative association between Epo and tumor progression/survival The optimal hemoglobin concentration at which to initiate erythropoietic therapy for chemotherapy-induced anemia ( CIA ) is not well defined . This r and omized , open-label , multicenter study evaluated the ability of darbepoetin alfa ( 300 microg every 3 weeks ) to maintain hemoglobin levels > or = 10 g/dl in patients with CIA ( hemoglobin > or = 10.5 g/dl and < or = 12.0 g/dl ) r and omized 1:1 to an immediate-intervention group ( received darbepoetin alfa immediately ) or observation group ( received darbepoetin alfa if hemoglobin fell to < 10 g/dl ) . In 201 evaluable patients , there was a significant difference between the two groups in the Kaplan-Meier proportion of patients with a hemoglobin decrease to < 10 g/dl during weeks 1 - 13 ( test period ) ( primary endpoint ) : 29 % for immediate-intervention patients versus 65 % for observation patients . Sixty-four patients in the observation group received darbepoetin alfa ( delayed-intervention subgroup ) . The Kaplan-Meier proportion of patients who received transfusions was lower in the immediate-intervention group than in the delayed-intervention subgroup ( 14 % versus 31 % for the test period ; 17 % versus 36 % over the whole study ) . The target hemoglobin level ( > or = 11 g/dl ) was achieved by a higher percentage of patients ( crude percentage ) in less time in the immediate-intervention group ( 94 % in 2 weeks ) than in the delayed-intervention subgroup ( 73 % in 6 weeks ) ; hemoglobin endpoints for the delayed-intervention subgroup were calculated from recalibrated study week 1 ( the date patients first received darbepoetin alfa ) . For both groups , a higher mean change in hemoglobin from baseline led to a greater improvement in Functional Assessment of Cancer Therapy-Fatigue scores . In conclusion , immediate intervention result ed in a significantly lower proportion of patients who experienced a decline in hemoglobin , lower requirement for transfusions , and greater proportion of patients achieving and maintaining the target hemoglobin level PURPOSE To evaluate the efficacy of recombinant erythropoietin ( EPO ) and granulocyte colony-stimulating factor ( G-CSF ) in reducing blood transfusion requirements and stimulating hematopoiesis in children with high-risk neuroblastoma . PATIENTS AND METHODS Thirty-eight patients given six cycles of intensive induction chemotherapy for high-risk neuroblastoma were r and omized to receive G-CSF ( n = 20 ) or G-CSF + EPO ( n = 18 ) . Cytokines were given subcutaneously each day , starting 24 hours after each chemotherapy cycle and continuing until 48 hours before the start of the next cycle . The primary end point was the effect of EPO on total red cell transfusion requirements during induction therapy . RESULTS Patients who received G-CSF + EPO had a higher red cell transfusion requirement ( median , 161.0 mL/kg ) than did those who received G-CSF alone ( median , 106.6 mL/kg ; P = .005 ) . In addition , among patients given transfusions for hemoglobin < or = 8 g/dL , those in the G-CSF + EPO group received more red cell transfusions than did those given G-CSF alone ( median per patient , 10 v 8 , respectively ; P = .044 ) . The two treatment groups had similar cumulative duration s of neutropenia , incidences of febrile neutropenia , platelet transfusion requirements , and numbers of platelet transfusions ; they also received induction chemotherapy for similar duration s and had similar probabilities of progression-free survival and overall survival . CONCLUSION The addition of EPO to the G-CSF regimen provides no benefit for patients receiving intensive induction chemotherapy for high-risk neuroblastoma BACKGROUND Erythropoietin corrects and prevents anemia and decreases the need for red blood cell ( RBC ) transfusions ; its impact on quality of life ( QOL ) of cancer patients receiving chemotherapy is not clear . PATIENTS AND METHODS 399 patients with solid tumors and Hb level of < or = 12 g/dl receiving chemotherapy were r and omized to receive or not 10,000 IU epoetin-alpha thrice weekly . QOL was measured by the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) scale and various subscales at baseline , at two months and at the end of the study . RESULTS Changes in the average QOL scores were similar in the two groups . The improvement in Hb levels was significantly higher for the epoetin-alpha group , with a decrease in transfusion requirements compared to the control group . CONCLUSION Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales , despite improving Hb levels and reducing transfusion requirements PURPOSE Chemotherapy-induced anemia is widely treated in the United States with darbepoetin alfa ( DA ) or epoetin alfa ( EA ) . This noninferiority study systematic ally compares efficacy and safety of DA and EA using common doses and schedules used in clinical practice . METHODS Patients had a diagnosis of nonmyeloid malignancy with > or = 8 weeks of planned chemotherapy , age > or = 18 years , and anemia ( hemoglobin < or = 11 g/dL ) . Patients were r and omly assigned 1:1 to DA 200 microg every two weeks ( Q2W ) or EA 40,000 units every week ( QW ) for up to 16 weeks with identical dose adjustment rules . Efficacy was assessed by the incidence of RBC transfusion ( Kaplan-Meier estimate ) . The definition of noninferiority was that the upper 95 % CI limit of the observed difference in RBC transfusions between groups was less than 11.5 % ; this noninferiority margin was based on the treatment effect observed in placebo-controlled EA studies . RESULTS Of 1,220 patients r and omly assigned , 1,209 received > or = one dose of the study drug . Common tumor types were lung ( 26 % ) , breast ( 21 % ) , and gastrointestinal ( 18 % ) . Transfusion incidence from week 5 to the end of the treatment phase ( the primary end point ) was 21 % in the DA group and 16 % in the EA group ; noninferiority was concluded because the upper 95 % CI limit of the difference between groups ( 10.8 % ) was below the prespecified noninferiority margin . Sensitivity analyses using alternate statistical methods and analysis sets yielded similar results . Hemoglobin , quality of life , and safety end points further support equivalency of the erythropoietic therapies . CONCLUSION This large , phase III study demonstrates comparable efficacy of DA Q2W and EA QW . Less frequent dosing offers potential benefits for patients , caregivers and health care providers The authors examined the relationship between changes in depression and anxiety levels with changes in fatigue levels among anemic patients with lung cancer who participated in a r and omized , double‐blind , placebo‐controlled clinical trial of darbepoetin alfa for the treatment of anemia This work was conducted to evaluate the effect of early intervention with epoetin alfa ( EPO ) on transfusion requirements , hemoglobin level ( Hb ) , quality of life ( QOL ) and to explore a possible relationship between the use of EPO and survival , in patients with solid tumors receiving platinum-based chemotherapy . Three hundred and sixteen patients with Hb12.1g/dL were r and omised 2:1 to EPO 10000 IU thrice weekly subcutaneously ( n = 211 ) or best supportive care ( BSC ) ( n = 105 ) . The primary end point was proportion of patients transfused while secondary end points were changes in Hb and QOL . The protocol was amended before the first patient was recruited to also prospect ively collect survival data . EPO therapy significantly decreased transfusion requirements ( P < 0.001 ) and increased Hb ( P < 0.005 ) . EPO-treated patients had significantly improved QOL compared with BSC patients ( P < 0.05 ) . Kaplan-Meier estimates showed no differences in 12-month survival ( P = 0.39 ) , despite a significantly greater number of patients with metastatic disease in the EPO group ( 78 % vs. 61 % , P = 0.001 ) . EPO was well tolerated . This study has shown that early intervention with EPO can result in a significant reduction of transfusion requirements and increases in Hb and QOL in patients with mild anemia during platinum-based chemotherapy BACKGROUND The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of st and ard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer . PATIENTS AND METHODS A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) every 3 weeks followed by four cycles of paclitaxel 175 mg/m(2 ) every 3 weeks ( EC→T ) , or three cycles of epirubicin 150 mg/m(2 ) every 2 weeks followed by three cycles of paclitaxel 225 mg/m(2 ) every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( E(dd)→T(dd)→CMF ) . The patients were r and omly assigned to receive darbepoetin or none . The primary objective was to demonstrate a superior disease-free survival ( DFS ) of E(dd)→T(dd)→CMF compared with EC→T. RESULTS Estimated 3-year DFS was 75.8 % with EC→T versus 78.8 % with E(dd)→T(dd)→CMF [ hazard ratio ( HR ) 1.14 ; P = 0.37 ] and overall survival ( OS ) 88.4 % versus 91.5 % ( HR 1.26 ; P = 0.237 ) . Three-year DFS was 74.3 % with darbepoetin versus 80.0 % without ( HR 1.31 ; P = 0.061 ) and OS 88.0 % versus 91.8 % ( HR 1.33 ; P = 0.139 ) . Patients with a pathologically documented complete response [ pathological complete response ( pCR ) ] had a significantly better DFS compared with those without achieving a pCR ( estimated 3-year DFS : 89.2 % versus 74.9 % ; HR 2.27 ; P = 0.001 ) . CONCLUSION Neoadjuvant dose-intensified chemotherapy compared with st and ard chemotherapy did not improve DFS , whereas the addition of darbepoetin might have detrimental effects on DFS In order to examine the influence of erythropoietin ( rHuEPO ) on serum hemoglobin levels , transfusion requirements , and quality of life in patients with gynecologic malignancies under polychemotherapy and chronic tumor anemia ( hemoglobin < 11 g/dl ) , we performed a prospect i ve , r and omized , double-blinded placebo-controlled clinical trial . Between October 1992 and October 1993 , 35 patients from 5 gynecologic departments were entered into this trial . Inclusion criteria were hemoglobin level < 11 g/dl , ferritin level > 29 ng/ml , stool negative for occult blood , and life expectancy for more than 3 months . Patients received either 150 U/kg body wt rHuEPO ( Erypo by Cilag-Janssen ) sc three times a week for 12 weeks ( n = 23 ) or a placebo ( n = 12 ) . If the hemoglobin levels of the 4th , 8th , or 12th week were > 2 g/dl above the baseline value and /or > 12 g/dl , the patient was classified as a responder . Patients who required blood transfusions ( hemoglobin < 8 g/dl , erythrocytes <3 x 10(6)/ml , or clinical symptoms of anemia ) were classified as nonresponders . A nonvali date d quality of life question naire was completed by the patient at the beginning of the treatment and then every fourth week before receiving chemotherapy . In the rHuEPO group 56.6 % of the patients responded to the treatment ( chi2 = 10.79 , P = 0.001 ) and only 5 patients ( 21.7 % ) required blood transfusions , whereas 8 of 12 patients in the placebo group ( 66.6 % ) had to be transfused ( chi2 = 6.81 , P = 0.009 ) . Quality of life did not differ significantly between the rHuEPO group and the placebo group of patients . Within the rHuEPO group those patients that responded showed a significant increase in physical activity after response in comparison to the preresponsive phase ( P = 0.02 , paired t test ) . We therefore concluded that rHuEPO significantly increases serum hemoglobin levels and decreases transfusions requirements while maintaining quality of life in patients with gynecological malignancies who are undergoing polychemotherapy BACKGROUND The recombinant human epoetin-a HX575 ( S and oz Pharmaceuticals GmbH/Hexal AG , Holzkirchen , Germany ) is the first biosimilar erythropoiesis-stimulating agent ( ESA ) with marketing authorization in Europe . The primary objective of the study was the evaluation of therapeutic equivalence in terms of hemoglobin ( Hb ) response of HX575 compared with the comparator product ( EPREX/ ERYPO , Janssen-Cilag/Ortho Biotech , Neuss , Germany ) in the long-term intravenous ( i.v . ) treatment of anemia in chronic renal failure patients on hemodialysis following a 1 : 1 dose conversion from the comparator product to HX575 . METHODS Hemodialysis patients with Hb levels of 10.0 - 13.0 g/dl were r and omized to either continue their current i.v . epoetin-a treatment or switch to HX575 . During treatment , epoetin dosages were titrated to maintain Hb values . The primary endpoint was the difference between treatment groups in the mean absolute change of Hb levels between baseline and evaluation period ( Weeks 25 - 28 ) . RESULTS Therapeutic equivalence of HX575 and the comparator epoetin-alpha , assessed during the evaluation period , was statistically confirmed : mean changes in Hb levels were 0.15 + /- 0.09 g/dl in the HX575 and 0.06 + /- 0.12 g/dl in the comparator epoetin-a group , with a difference between groups of 0.08 g/dl ( 95 % confidence interval : -0.17 ; 0.34 ) . Hb levels and epoetin dosages remained stable throughout the entire study period of 56 weeks . The long-term safety profile of HX575 was similar to that of the comparator epoetin-alpha . No antibody formation was detected . CONCLUSIONS The study demonstrated therapeutic equivalence of biosimilar HX575 to the comparator epoetin-a , together with a comparable safety profile This r and omised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin ( rhEPO ) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy . The patients were r and omly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously , three times a week , or open control . Patients also received up to 6 cycles of carboplatin or cisplatin , alone or in combination with other cytotoxic agents . Intention-to-treat analysis showed that 39.4 % of patients in the control group received at least one blood transfusion , compared with 9.2 % of patients treated with rhEPO . Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl ( P<0.001 and < 0.05 , respectively ) . A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle , as well as a low baseline serum erythropoietin concentration , predicted a low transfusion need in rhEPO-treated patients but not in controls . During the study , 103 patients suffered at least one adverse event , but no serious , and only nine non-serious adverse events were considered possibly related to rhEPO therapy . These results indicate that treatment with rhEPO prevents anaemia , it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy , and it is well tolerated . A starting dose of 150 U/kg of rhEPO , three times a week , may be recommended PURPOSE This r and omized , double-blind , placebo-controlled trial ( N93 - 004 ) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy . Survival was assessed for 3 years . The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles . RESULTS The trial was terminated prematurely after 224 of a projected 400 patients were accrued . Baseline characteristics were similar between groups . Epoetin alfa and placebo patients ( n = 109 and n = 115 , respectively ) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL , respectively . Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles ( 72 % and 67 % , respectively ; 95 % CI of difference , -6 % to 18 % ) and after completion of chemotherapy ( 60 % and 56 % , respectively ; 95 % CI of difference , -9 % to 17 % ) . Epoetin alfa and placebo groups had similar median overall survival ( 10.5 and 10.4 months , respectively ) and overall mortality ( 91.7 % and 87.8 % , respectively ; hazard ratio , 1.172 ; 95 % CI , 0.887 to 1.549 ; P = .264 ) . Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients , but decreased substantially in placebo patients . Fewer epoetin alfa patients than placebo patients required transfusion . CONCLUSION These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival . However , the early trial closure makes these conclusions preliminary The purpose of this study was to assess whether the administration of recombinant human erythropoietin ( rHuEPO ) would correct anemia and improve the quality of life ( QOL ) in cancer patients receiving chemotherapy . One hundred twenty-two patients with hemoglobin < /=11.0 g/dl were r and omized to receive rHuEPO 10,000 U three times weekly ( n = 61 ) or no additional treatment ( n = 61 ) . Response was assessed by measuring changes in hemoglobin level and QOL . QOL was evaluated before each cycle of chemotherapy at baseline , Week 4 , and Week 12 using two separate self-report question naires . The analyses indicated that the rHuEPO-treated patients experienced significantly less fatigue ( P < 0.05 ) than their control group counterparts , and reported significantly higher scores on energy level ( P < 0.05 ) , ability to perform daily activities ( P < 0.01 ) , and overall QOL ( P < 0.05 ) . The overall change in hemoglobin level was significantly greater in the rHuEPO group than in the control group ( 1.7 g/dl versus 0.3 g/dl , P < 0.001 ) . rHuEPO effectively corrects anemia and significantly improves QOL in patients with solid tumors receiving chemotherapy ABSTRACT Objective : To evaluate if a darbepoetin alfa correction/maintenance dosing regimen is non-inferior to a weekly regimen with respect to red blood cell transfusion requirements in patients with chemotherapy-induced anemia ( CIA ) . Research design and methods : In this r and omized , active-controlled , double-blind phase 3 trial , CIA patients were r and omized 1 : 1 to receive darbepoetin alfa in either a correction/maintenance schedule ( 4.5 μg/kg weekly for 4 weeks followed by 4.5 μg/kg every 3 weeks ( Q3W ) ) or a weekly schedule ( 2.25 μg/kg weekly ) . The primary endpoint was the transfusion incidence during weeks 1–16 . Non-inferiority was to be concluded if the upper limit of the 95 % confidence interval ( CI ) of the difference in transfusion incidence between treatment groups was below 12.5 % . Hematologic responses and safety profiles were also compared . Results : Transfusion incidence ( 95 % CI ) during weeks 1–16 was 37 % ( 32–42 ) and 38 % ( 32–43 ) in the weekly and correction/maintenance groups , respectively . The difference ( 95 % CI ) in transfusions was 0.4 % ( –7.0 to 7.8 ) , demonstrating non-inferiority between treatment groups . Similar percentages in both groups achieved and maintained hemoglobin in a target range of 11–13 g/dL and had clinical ly meaningful FACT‑F score improvements . The median ( range ) time to hemoglobin response was 10 ( 1–17 ) weeks and 12 ( 2–17 ) weeks in the weekly and correction/maintenance groups , respectively . Both groups had similar safety profiles . Conclusions : A correction/maintenance schedule with its initial two-fold higher weekly dosing and subsequent Q3W dosing yielded outcomes similar to those observed with a weekly schedule . Although correction/maintenance dosing provided no incremental clinical benefit , Q3W dosing could provide benefits of convenience and facilitate patient compliance Chemotherapy‐related anemia is prevalent among patients with hematologic malignancies . A r and omized , open‐label , multicenter trial of early versus late epoetin alfa in this population was conducted , focusing on quality of life ( QOL ) BACKGROUND Immunochemotherapy with rituximab and cyclophosphamide , doxorubicin , vincristine , and prednisone ( R-CHOP ) has become the st and ard of care for elderly patients with diffuse large B-cell lymphoma . We aim ed to ascertain if a dose-dense R-CHOP regimen administered every 2 weeks ( R-CHOP14 ) was superior to the st and ard 3-week schedule ( R-CHOP21 ) . METHODS We did a r and omised phase 3 trial at 83 centres in four countries . 602 patients aged 60 - 80 years with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor ( age-adjusted international prognostic index ≥ 1 ) were eligible for the study . We r and omly allocated individuals to R-CHOP-ie , rituximab ( 375 mg/m(2 ) ) , cyclophosphamide ( 750 mg/m(2 ) ) , doxorubicin ( 50 mg/m(2 ) ) , vincristine ( 1.4 mg/m(2 ) , up to 2 mg ) all on day 1 , and prednisone 40 mg/m(2 ) daily for 5 days-administered every 14 days ( n=304 ) or every 21 days ( n=298 ) for eight cycles . We did permuted-block r and omisation ( block size four , allocation ratio 1:1 ) stratified by centre and number of adverse prognostic factors . The primary endpoint was event-free survival . Our analysis was of the intention-to-treat population , and we present the final analysis . This study is registered with Clinical Trials.gov , number NCT00144755 . FINDINGS Two patients allocated R-CHOP21 were ineligible for the study and were excluded from analyses . After median follow-up of 56 months ( IQR 27 - 60 ) , 3-year event-free survival was 56 % ( 95 % CI 50 - 62 ) in the R-CHOP14 group and 60 % ( 55 - 66 ) in the R-CHOP21 group ( hazard ratio 1.04 , 95 % CI 0.82 - 1.31 ; p=0.7614 ) . Grade 3 - 4 neutropenia occurred in 224 ( 74 % ) of 304 patients allocated R-CHOP14 and 189 ( 64 % ) of 296 assigned R-CHOP21 , despite increased use of granulocyte colony-stimulating factor in the R-CHOP14 group compared with the R-CHOP21 group . 143 ( 47 % ) patients in the R-CHOP14 group received at least one red-blood-cell transfusion versus 93 ( 31 % ) in the R-CHOP21 group ( p=0.0001 ) . 35 ( 12 % ) patients allocated R-CHOP14 received at least one platelet transfusion versus 25 ( 8 % ) assigned R-CHOP21 ( p=0.2156 ) . 155 ( 51 % ) patients who were assigned R-CHOP14 had at least one serious adverse event compared with 140 ( 47 % ) who were allocated R-CHOP21 . INTERPRETATION In elderly patients with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor , a 2-week dose-dense R-CHOP regimen did not improve efficacy compared with the 3-week st and ard schedule . The frequency of toxic side-effects was similar between regimens , but R-CHOP14 was associated with increased need for red-blood-cell transfusion . FUNDING Groupe d'Etude des Lymphomes de l'Adulte ( GELA ) , Amgen PURPOSE Cancer patients frequently experience anemia as a consequence of myelosuppressive therapy or bone marrow invasion . PATIENTS AND METHODS A risk model for chemotherapy-induced severe anemia requiring RBC transfusions ( SARRT ) within 31 days after the administration of chemotherapy was delineated in the cohort of cancer patients treated with chemotherapy in the Department of Medicine of Centre Léon Bérard in 1996 ( CLB-1996 ) . The risk model was tested on a series of 797 patients treated in 1997 ( CLB-1997 ) and on 295 patients included in a multicenter prospect i ve series ( ELYPSE 1 ) . RESULTS One hundred seven of the 1,051 patients of the CLB-1996 cohort ( 10 % ) experienced SARRT . In univariate analysis , only female sex , performance status greater than 1 , hemoglobin level less than 12 g/dL before chemotherapy on day 1 ( d1 ) , and d1 lymphocyte count < or = 700/microL significantly correlated with the risk of SARRT . Using logistic regression , d1 hemoglobin level less than 12 g/dL ( odds ratio [ OR ] = 14.0 ; 95 % confidence interval [ CI ] , 7 to 30 ) , performance status greater than 1 ( OR = 2.2 ; 95 % CI , 1.4 to 3.5 ) , and d1 lymphocyte count < or = 700/microL ( OR = 1.7 ; 95 % CI , 1 . 1 to 2.6 ) were identified as independent risk factors for SARRT . These three factors were given arbitrary risk coefficients of 3 , 1 , and 1 respectively , and a risk score for each individual patient was obtained by adding the coefficients . The calculated probability of RBC transfusions was 30 % for patients with a score > or = 4 , and 11 % , 4 % , and 1 % in patients with a score of 2 or 3 , 1 , and 0 respectively . This model was then tested and vali date d in the CLB-1997 and ELYPSE 1 series . CONCLUSION This risk index could be useful to identify patients at high risk for chemotherapy-induced SARRT who might be appropriate c and i date s for prophylactic erythropoietin treatment An important clinical question is the relative efficacy of the most common dosages of darbepoetin alfa ( Aranesp ; Amgen Inc. ; Thous and Oaks , CA ) 200 microg every 2 weeks ( Q2W ) and epoetin alfa ( Procrit ; Ortho Biotech Products , LP ; Raritan , NJ ) 40,000 U weekly ( QW ) for the treatment of chemotherapy-induced anemia . We design ed three concurrent r and omized , open-label , multicenter , identical trials ( with the exception of tumor type criteria of breast , gynecologic , or lung cancer ) of darbepoetin alfa and epoetin alfa in patients with chemotherapy-induced anemia to vali date the Patient Satisfaction Question naire for Anemia ( PSQ-An ) treatment tool and to compare the efficacies and safety profiles of these two agents . In each trial , patients were r and omized 1:1 to receive either darbepoetin alfa at a dose of 200 microg Q2W or epoetin alfa at a dose of 40,000 U QW for up to 16 weeks . The PSQ-An was assessed for validity , feasibility , and reliability . Secondary clinical endpoints were analyzed using the primary analysis set . Both individual trial analyses and a protocol -specified combined analysis of data from all three trials were conducted . Overall , 312 patients ( 157 darbepoetin alfa ; 155 epoetin alfa ) were r and omized and received study drug . Baseline characteristics were similar in both treatment groups in each trial and overall . The PSQ-An was valid , feasible , and reliable . In general , no difference between treatment groups was observed for hemoglobin- and transfusion-based endpoints in each individual trial or in the combined analysis . From exploratory analyses , achievement and maintenance of a hemoglobin target range ( 11 - 13 g/dl ) were similar in both groups . No differences in safety were observed . With the PSQ-An , formal comparisons of the impact of anemia therapies on patients and caregivers can be made in future prospect i ve studies . Further , darbepoetin alfa ( 200 microg Q2W ) and epoetin alfa ( 40,000 U QW ) appear to achieve comparable clinical and hematologic outcomes One hundred twenty-one anemic , transfusion-dependent patients with multiple myeloma ( MM ) or low- grade non-Hodgkin 's lymphoma ( NHL ) were r and omly allocated to receive ( a ) recombinant human erythropoietin ( rhEPO ) 10,000 U/d subcutaneously 7 days a week ( fixed dose group ) ( n = 38 ) , or ( b ) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step-wise escalation of the rhEPO dose ( titration group ) ( n = 44 ) , or ( c ) no rhEPO therapy ( control group ) ( n = 39 ) . The total treatment period was 24 weeks . There were no differences between the three groups with regard to baseline clinical , demographic , or health status measures . The cumulative response frequency , defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by > 20 g/L , was 60 % in both rhEPO treatment groups and 24 % in the control group ( P = .01 and .02 , respectively , log rank test ) . For patients in the titration group the response rate on the first dose level ( 2,000 U/d ) was only 14 % . Cox 's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentration > or = 100 x 10(9)/L were significant predictors for response to rhEPO therapy ( P < .01 ) . Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response . Treatment with rhEPO was well tolerated . We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency . An initial dose of 5,000 U/d subcutaneously may be recommended PURPOSE Previous trials have suggested a quality -of-life ( QOL ) improvement for anemic cancer patients treated with erythropoietin , but few used QOL as the primary outcome . We design ed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung ( NSCLC ) . PATIENTS AND METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was conducted . The proposed sample size was 300 patients . Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin ( Hgb ) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo , targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks . RESULTS Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been r and omly assigned ( 33 to the active arm and 37 to the placebo arm ) . This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial ( 63 v 129 days ; hazard ratio , 1.84 ; P = .04 ) . The Steering Committee closed the trial . Patient numbers compromised the interpretation of the QOL analysis , but a positive Hgb response was noted with epoetin alfa treatment . CONCLUSION An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa . Although infrequent , other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely INTRODUCTION ADVANCED CANCER is frequently associated with significant anaemia which may be worsened by the administration of chemotherapy with myelotoxic agents such as methotrexate or nephrotoxic agents such as cisplatin . Although anaemia in cancer patients may be multifactorial in origin , it is often categorised as the anaemia of chronic disease ( ACD ) [ 1,2 ] . ACD is characterised by erythroid hypoplasia of the bone marrow , a modest decrease in red cell survival , decreased bone marrow reutilization of iron , and inappropriately low erythropoietin levels for the degree of anaemia [ 2 ] . Consistent with this A C D model , i napp rop r i a t e ly low se rum erythropoietin levels for the degree of anaemia have recently been documented in cancer patients [ 3 ] . The symptomato logy of anaemia may con t r ibu t e substantially to the overall lack of well-being that cancer patients frequently experience during their disease process . The t ransfusions often required for pal l ia t ion of these symptoms carry significant risks . There is an estimated 20 % probability of some associated adverse effect including fever , chills , rash , urticaria and exposure to hepatitis [ 4 ] . The scope of this problem is substantial when one considers that the annual transfusion estimate for this patient group in the U.S.A. alone is one million units of red blood cells/whole blood [ 5 ] . The observation that , at any given haemoglobin level , serum erythropoiet in levels tend to be lower in cancer patients than in iron deficiency patients [ 3 ] suggests that anaemia in cancer is at least partially due to a relative deficiency of e ry thropoie t in . In c o n j u n c t i o n with this observation , recent work demonstrating both the eft]caw and safety of recombinant human erythropoietin ( r-HuEPO ) in increasing haematocrit in anaemic patients with chronic renal failure [ 6,7 ] and in anaemic , zidovudine (AZT)-treated HIVinfected patients [ 8 ] offers the possibility that exogenous erythropoietin may also be an effective treatment for anaemia in cancer patients . To test this possibility , we conducted a series of double-blind , placebo-controlled trials using r-HuEPO in anaemic cancer patients in three different patient population s to examine the safety of r-HuEPO treatment , and its impact on haematocrit , t ransfusion requi rements and quality of life . The three populat ions were : pat ients receiving no chemotherapy , pa t i en t s rece iv ing cyclic n o n c i s p l a t i n c o n t a i n i n g chemothe rapy and pa t ients receiving cyclic c isp la t incontaining chemotherapy Abstract Introduction : A 16-week , open-label , multicentre , r and omised trial of weekly epoetin alfa 40 000 units versus biweekly darbepoetin alfa 200 µg among 358 patients with solid-tumour cancers and chemotherapy-induced anaemia demonstrated superior haematological outcomes with epoetin alfa . We sought to compare re source use , costs and clinical outcomes between treatment groups and report the results using a cost-consequences framework . Methods : Pre-specified methods were used to assign costs ( $ US , year 2004–5 values ) to medical re sources and patient time using a societal perspective . Costs for inpatient care , outpatient care and physician services were based on US Medicare reimbursement rates . Indirect costs assigned to patient time spent receiving study medication were based on the mean hourly wage in the US . In the base-case analysis , the average wholesale price was used to assign costs to medications . Clinical outcomes included all haemoglobin levels and transfusions recorded throughout the trial . Sensitivity analyses were performed to evaluate the impact of different costing methods , cost sources , perspectives and methods to assign haemoglobin values following a blood transfusion . Results : Over a mean follow-up duration of 11.8 weeks , the average cost of study medications and their administration was the single largest component of total costs and was similar between groups ( epoetin alfa $ US5979 and darbepoetin alfa $ US5935 , difference $ US44 ; 95 % CI −590 , 692 ) . There were no significant differences in the proportions of patients hospitalised ( epoetin alfa 24.6 % , darbepoetin alfa 22.0 % ; p = 0.57 ) . Patients r and omised to epoetin alfa experienced more inpatient days , on average , than patients r and omised to darbepoetin alfa ( 2.6 vs 1.6 , 95 % CI for the difference , 0.07 , 2.27 ) . However , with regard to transfusions , patients in the epoetin alfa arm required fewer units of blood than patients in the darbepoetin alfa arm ( 0.46 vs 0.88 , 95 % CI for the difference −0.77 , −0.08 ) . Mean total costs , comprising costs for study medications and their administration , inpatient care , transfusions , unplanned radiation therapy , haematology and laboratory services , chemotherapy and non-chemotherapy drugs and indirect costs were $ US14 976 in the epoetin alfa arm compared with $ US14 101 in the darbepoetin alfa arm , a difference of $ US875 ( 95 % CI for difference −849 , 2607 ) , of which 98 % of the difference was attributable to higher inpatient costs in the epoetin alfa arm ( $ US2374 vs $ US1520 ; 95 % CI for difference −33 , 1955 ) . Assessment s of multiple clinical measures demonstrated improved outcomes with epoetin alfa relative to darbepoetin alfa . Conclusion : Most clinical outcome measures suggested greater improvement with epoetin alfa relative to darbepoetin alfa , but most costs for both agents appeared similar . Decision makers must evaluate the differences in costs and efficacy measures that are most relevant from their perspectives This dose-finding , placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks ( Q3W ) to anaemic patients receiving chemotherapy . In part A , patients ( haemoglobin < /=110 g/l ) were r and omised in a 1:4 ratio to receive 1 of 6 doses of darbepoetin alfa ( 4.5 , 6.75 , 9.0 , 12.0 , 13.5 and 15.0 microg/kg ) or placebo Q3W for 12 weeks . In part B , patients received open-label darbepoetin alfa . Patients ( n=249 ) were evaluated for safety , haemoglobin endpoints and red blood cell ( RBC ) transfusions . Darbepoetin alfa given at doses ranging from 4.5 to 15.0 microg/kg Q3W was well tolerated and comparable to placebo in terms of safety . No neutralising antibodies were detected . All doses ( from 4.5 to 15 microg/kg ) reduced transfusions compared with placebo , and result ed in > 50 % of patients achieving a haematopoietic response . Administration of darbepoetin alfa Q3W has a tolerable safety profile and effectively ameliorates anaemia due to chemotherapy Background : Recombinant human epoetin alfa , HX575 , is the first biosimilar erythropoiesis-stimulating agent ( ESA ) with European marketing authorisation . The primary objective of this double-blind , r and omised , multicentre study was to assess the efficacy and safety of HX575 in treating chemotherapy-associated symptomatic anaemia in patients with solid tumours . Patients and Methods : The patients ( n = 114 ) were treated with HX575 or active control ( epoetin alfa ) at 150 IU/kg body weight 3 times weekly for 12 weeks , increased to 300 IU/kg body weight 3 times weekly if the haemoglobin/reticulocyte increase was insufficient after 4 or 8 weeks . Results : With HX575 , haemoglobin increased by ≥20 g/l in 62 % ( 37/60 patients ) . The confidence interval ( 48.2 % , 73.9 % ) was entirely above the pre-defined 30 % threshold . Both groups showed similar results for safety profiles and secondary efficacy parameters . Transfusion requirements were 32 % ( 19/60 ) ( HX575 ) and 38 % ( 13/34 ) ( epoetin alfa ) . Conclusions : In treating chemotherapy-associated symptomatic anaemia in patients with solid tumours , the biosimilar ESA , HX575 , is efficacious with a safety profile as expected for the therapeutic area Patients with cervical cancer frequently suffer from anemia . This two-stage , adaptive- design study investigated the effect of anemia correction with epoetin beta on treatment outcomes . Patients with stage IIB – IVA cervical cancer received radiochemotherapy ( RCT ) and were r and omized to epoetin 150 IU/kg three times weekly ( n = 34 ) or st and ard care ( control ; n = 40 ) for up to 12 weeks . Primary end point for stage 1 aim ed to establish a correlation between anemia correction and treatment failure ( no complete response or relapsing within 6 months after RCT initiation ) as a proof of concept before moving into stage 2 . Secondary end points included progression/relapse-free survival , overall survival , response to RCT , hemoglobin ( Hb ) response , and safety . Median baseline Hb was 11.4 and 11.6 g/dL in epoetin and control groups , respectively . At treatment end point , median Hb increased by 1.3 g/dL with epoetin , but decreased by 0.7 g/dL in the control group ( P < 0.0001 ) . No significant correlation between Hb increase and treatment failure was demonstrated . There were no significant differences between epoetin and control groups in progression/relapse-free survival ( 29.4 % vs 32.5 % patients with events ; P = 0.96 ) , overall survival ( 23.5 % vs 12.5 % patients with events ; P = 0.22 ) or overall complete response ( 53 % vs 58 % ; P = 0.86 ) . Adverse events were well matched between groups . This study shows that epoetin beta rapidly , effectively , and safely increases Hb levels in patients with cervical cancer receiving RCT . No positive correlation of Hb increase and improvement in clinical outcomes could be demonstrated ABSTRACT Objective : To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia . Research design and methods : Preliminary data from an ongoing r and omized , multicenter , 16‐week , open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response ( ≥ 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation ) . Measures of efficacy were compared between patients with early hemoglobin response and those without . Sensitivity analyses were then performed to evaluate the impact of various methods for h and ling censored data and hemoglobin values following blood transfusion . Main outcome measures : Efficacy measures included : the proportion of patients with a ≥ 1 g/dL increase in hemoglobin by 4 weeks or a ≥ 2 g/dL increase by 8 weeks ; mean hemoglobin levels at 4 , 8 , 12 , and 16 weeks ; area under the curve for change in hemoglobin level ; proportion of patients who required a blood transfusion after 4 weeks ; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL ; and proportion of patients who never had a hemoglobin level within this range . Results : A total of 274 patients were included ( 66.1 % female , mean age 62.4 ) , of whom 48.9 % had an early hemoglobin response and 51.1 % did not . Mean duration of follow-up was 10.1 ± 5.05 weeks . All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response . The findings were robust across sensitivity analyses . Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics , causality can not be inferred . Conclusions : Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects BACKGROUND Patients with advanced cancer frequently experience clinical ly significant anemia , which is often exacerbated by myelosuppressive chemotherapy . Consistent with the anemia of chronic disease , studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients . Myelosuppressive chemotherapy impairs erythropoiesis , which may not fully recover between treatment cycles . Recombinant human erythropoietin ( rHuEPO ) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine ( AZT ) and in patients with chronic renal failure . PURPOSE This study was design ed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy ( excluding cisplatin ) . METHODS We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospect i ve multicenter , double-blind , placebo-controlled trial . The patients were r and omly assigned to receive either rHuEPO ( 150 U/kg ) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40 % . If the hematocrit reached this target level before 12 weeks , the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study . Response to rHuEPO therapy was assessed by measuring changes in hematocrit level , transfusion requirements , and quality of life . Quality -of-life assessment was based on patients ' responses to question naires before and after the courses of therapy . RESULTS The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant ( P = .0001 ) as measured by percentage point of change from baseline to final evaluation , by an increase in hematocrit level of six percentage points or more unrelated to transfusion , and by a rise in hematocrit level to 38 % or more unrelated to transfusion . There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients ( 0.91 U versus 1.65 U ; P = .056 ) . In addition , rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities ( P < or = .05 ) . The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis ( P < .05 ) and diarrhea ( P = .05 ) in the rHuEPO-treated group . CONCLUSIONS We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer Recombinant human erythropoietin ( r-HuEPO ) corrects cancer-related anemia and , thereby , improves quality of life . The purpose of the present study was to measure the impact of erythropoietin on hemoglobin and mood state in patients with metastatic breast cancer and mild anemia ( Hgb < 12.0 g/dL ) . Women were r and omized to receive usual care ( G1 ) or usual care plus r-HuEPO ( G2 ) . Usual care included transfusions as necessary and fatigue education . R-HuEPO was begun at 40,000U subcutaneously per week . At 4 weeks , the dose was increased to 60,000U if Hgb had not increased > or = 1.0 g/dL. The drug was discontinued at 8 weeks if hemoglobin improvement was < 1.0 g/dL. The study was terminated early ( n = 27 , G1 = 13 , G2 = 14 ) when 4/14 ( 28.5 % ) subjects in G2 developed thrombotic events ( deep vein thrombosis [ DVT ] in 1 ; DVT plus pulmonary embolism [ PE ] in 1 ; DVT plus PE 1 month after drug discontinuation in 1 ; and brachial vein thrombosis with infected Mediport in 1 ) . In all four patients , Hgb levels were normal at the time of the event . No patient in G1 developed a thrombotic event . There were no significant differences in demographic characteristics or current chemotherapy regimen in G1 vs. G2 . The decision to terminate the trial was made after considerable deliberation . The increased incidence of thrombotic events in the r-HuEPO ( G2 ) arm of this study exceeds that in prior studies in this population and prior r-HuEPO trials . This may relate to the administration of r-HuEPO in this high-risk population , but the small sample size and possible predisposing risk factors preclude definitive conclusions Aims and Background More than 60 % of patients with metastatic breast cancer receiving non-platinum-based chemotherapy experience anemia , which is associated with fatigue and impaired quality of life . Epoetin alfa treatment in patients with a variety of malignancies has been shown to decrease transfusion requirements and improve hemoglobin levels and quality -of-life efficacy parameters . Patients Retrospective subgroup analyses were performed in patients with breast cancer who were part of a multinational , r and omized ( 2:1 ) , double-blind , placebo-controlled trial of anemic cancer patients ( n = 375 ) undergoing non-platinum-based chemotherapy . Results In the breast cancer sub population ( n = 114 , 48 % with stage IV disease at baseline ) , the hemoglobin increase was greater for epoetin alfa patients than placebo patients ( 2.3 versus 0.9 g/dL ) . Epoetin alfa patients had lower transfusion requirements ( 28.2 % versus 33.3 % ) , improvement or preservation versus deterioration of quality of life , and a higher proportion of responders ( patients achieving a ≥2 g/dL increase in hemoglobin levels unrelated to transfusion ) ( 68.0 % versus 22.9 % for placebo ) . The results were similar to those observed in the full study cohort , where statistical analyses showed the differences to be significant ( P < 0.05 for all ) . Epoetin alfa treatment was well tolerated . Although the study was not design ed or powered for survival as an endpoint , Kaplan-Meier estimates for the full cohort showed a trend in overall survival favoring epoetin alfa treatment ( P= 0.13 , log rank test ) ; a similar benefit was seen in the breast cancer sub population . Conclusions In the full study cohort and the breast cancer sub population , epoetin alfa effectively treated anemia ( increased hemoglobin levels and decreased transfusion requirements ) and improved or preserved quality of life . Results concerning potential survival benefits support further study of epoetin alfa in anemic cancer patients BACKGROUND Anemia is a common side effect of anticancer chemotherapy . Blood transfusion , previously the only available treatment for chemotherapy-induced anemia , may result in some clinical or sub clinical adverse effects in the recipients . Recombinant human erythropoietin ( rhEPO ) provides a new treatment modality for chemotherapy-induced anemia . PATIENTS AND METHODS To evaluate the effect of rhEPO on the need for blood transfusions and on hemoglobin ( Hb ) concentrations , 227 patients with solid tumors and chemotherapy-induced anemia were enrolled in a r and omized , controlled , clinical trial . Of 189 patients evaluable for efficacy , 101 received 5000 IU rhEPO daily s.c . , while 88 patients received no treatment during the 12-week controlled phase of the study . RESULTS The results demonstrate a statistically significant reduction in the need for blood transfusions ( 28 % vs. 42 % , P = 0.028 ) and in the mean volume of packed red blood cells transfused ( 152 ml vs. 190 ml , P = 0.044 ) in patients treated with rhEPO compared to untreated controls . This effect was even more pronounced in patients receiving platinum-based chemotherapy ( 26 % vs. 45 % , P = 0.038 ) . During the controlled treatment phase , the median Hb values increased in the rhEPO patients while remaining unchanged in the control group . The response was seen in all tumor types . CONCLUSIONS RhEPO administration at a dose of 5000 IU daily s.c . increases hemoglobin levels and reduces transfusion requirements in chemotherapy-induced anemia , especially during platinum-based chemotherapy OBJECTIVE This analysis of the results of a r and omized , controlled trial evaluating the effects of epoetin alfa ( EPO ) therapy on transfusion requirements , hemoglobin ( Hb ) , and quality of life ( QOL ) in patients with cancer receiving platinum-based chemotherapy was conducted to evaluate the effect of initial Hb level on study outcomes . METHODS Patients with Hb levels < or = 12.1 g/dl were r and omized 2:1 to receive EPO , 10,000 U three times weekly s.c . or best supportive care ( BSC ) until 4 weeks after their last chemotherapy cycle . For this analysis , patients were stratified by baseline Hb level ( < or = 9.7 g/dl , > 9.7 g/dl to < or = 10.5 g/dl , > 10.5 g/dl to < or = 11.3 g/dl , and > 11.3 g/dl to < or = 12.1 g/dl ) , and study results were reanalyzed . RESULTS Significantly fewer EPO patients than BSC patients with initial Hb levels > 9.7 g/dl to < or = 12.1 g/dl required transfusions . EPO maintained Hb levels throughout the study for patients with Hb levels > 11.3 g/dl to < or = 12.1 g/dl , compared with a decrease with BSC . For patients with baseline Hb levels > 10.5 g/dl , for whom the mean changes from baseline to last assessment were measured by the Cancer Linear Analogue Scale assessment s of energy and overall QOL as well as by the Functional Assessment of Cancer Therapy (FACT)-Fatigue and FACT-An Anemia subscale , QOL scores were significantly greater with EPO than with BSC . QOL declined in patients receiving BSC , and the mean decreases in QOL scores were greater for BSC patients with baseline Hb levels > 10.5 g/dl , compared with the overall BSC group . CONCLUSION In patients with cancer receiving platinum-based chemotherapy and with baseline Hb levels > 10.5 g/dl , early intervention with EPO reduces transfusions , maintains Hb level , and maintains or improves QOL . This study supports the positive effects of early intervention when analyzed according to initial Hb value Objectives : Platinum compounds are commonly associated with significant anemia . Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy . We conducted a r and omized , open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia ( hemoglobin < 10 g/dl ) in patients with solid tumors receiving platinum-based chemotherapy . Methods : One hundred forty-four patients with hemoglobin < 13 g/dl were included in this study ( 72 in each arm ) . Patients in the treatment arm received 10,000 U of recombinant human erythropoietin ( rHuEPO ) thrice weekly s.c . during platinum-based chemotherapy , while patients in the control arm received no treatment . Results : All patients were evaluable for efficacy . Transfusions were reduced by the administration of rHuEPO ( 15.3 vs. 33.3 % , p = 0.019 ) , and fewer patients developed significant anemia ( 16.6 vs. 45.8 % , p < 0.0001 ) . Subgroup analysis showed that patients with observed to predicted ( O/P ) serum erythropoietin levels ≤0.9 and responders to chemotherapy benefited from erythropoietin administration in contrast to patients with O/P > 0.9 or non-responders . Conclusions : rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy PURPOSE Epoetin alfa administered at 40,000 U once weekly ( qw ) to anemic cancer patients receiving chemotherapy increases hemoglobin levels , improves quality of life ( QOL ) , and reduces transfusions . The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated . METHODS Breast cancer patients ( N = 354 ) receiving chemotherapy were r and omly assigned in 1:1 ratio to epoetin alfa ( 40,000 U qw ) or st and ard of care ( SOC ) . QOL was assessed at baseline and week 12 . Hemoglobin responses , transfusion requirements , and prognostic factors for responses were measured . RESULTS At week 12 , Functional Assessment of Cancer Therapy-Anemia ( FACT-An ; mean , 2.16 + /- 12.84 for epoetin alfa v -4.43 + /- 13.42 for SOC ) and FACT-An fatigue ( mean , 1.85 + /- 10.52 for epoetin alfa v -3.55 + /- 11.14 for SOC ) change scores were significantly higher in the epoetin alfa group ( P < .0001 ) . Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC : 52.0 % v 5.1 % and 65.7 % v 6.3 % , respectively ( P < .0001 for both comparisons ) . Percentage transfused was significantly lower in the epoetin alfa group compared with SOC ( 8.6 % v 22.9 % ) . More than 90 % of patients did not require a dose increase and 28.7 % had a dose reduction . CONCLUSION Epoetin alfa administered at 40,000 U qw is effective in improving QOL , maintaining hemoglobin level , and reducing transfusion requirements in breast cancer patients . The high effectiveness observed could be attributed in part to early treatment with epoetin alfa Effects of epoetin alfa on transfusions , haemoglobin ( Hb ) and quality of life ( QOL ) were evaluated in a placebo‐controlled study of 145 patients with multiple myeloma and anaemia ( Hb < 11 g/dl ) . During the 12‐week , double‐blind phase , patients received 150 IU/kg epoetin alfa or a matching volume of placebo subcutaneously three times weekly ; the dose ( or volume ) was doubled at week 4 if Hb response was inadequate . Patients completing this phase could enter the subsequent optional 12‐week phase of open‐label epoetin alfa treatment . During double‐blind treatment , epoetin alfa significantly decreased the incidence of transfusion compared with placebo ( 28 % vs. 47 % , P = 0·017 ) , regardless of patients ' transfusion history , and increased mean Hb ( 1·8 g/dl vs. 0·0 g/dl , P < 0·001 ) . Univariate analysis showed significant ( P ≤ 0·05 ) improvement in more QOL measures with epoetin alfa than with placebo ; multivariate analysis discerned no between‐treatment differences . Significantly ( P = 0·038 ) more epoetin alfa vs. placebo patients had improved performance scores . At the end of the open‐label treatment phase , patients who had continued epoetin alfa maintained Hb status , and placebo patients who were switched to epoetin alfa had mean Hb increases of 2·4 g/dl . Adverse events were similar between treatment groups . Epoetin alfa proved effective and well tolerated for treating anaemia in patients with multiple myeloma BACKGROUND Current chemotherapy regimens for breast cancer result in high incidences of anemia , which can be treated with erythropoietic agents . The relative efficacy of darbepoetin alfa and epoetin alfa was explored in this phase II , open-label , r and omized , multicenter trial in anemic patients with breast cancer receiving chemotherapy . PATIENTS AND METHODS Patients were r and omized at a 1:1 ratio to receive darbepoetin alfa 200 microg every 2 weeks ( n = 72 ) or epoetin alfa 40,000 U weekly ( n = 69 ) for < or = 16 weeks . Clinical and hematologic endpoints and validation of a novel patient satisfaction question naire for anemia treatment were evaluated for all patients r and omized to receive > or = 1 dose of study drug . RESULTS Baseline characteristics were generally similar between treatment groups . Mean changes in hemoglobin ( Hb ) level from baseline were similar at 1.9 g/dL for darbepoetin alfa and 1.7 g/dL for epoetin alfa . Hematopoietic responses ( > or = 2 g/dL increase in Hb level from baseline or Hb level > or = 12 g/dL ) were also similar between groups ( 88 % for darbepoetin alfa and 81 % for epoetin alfa ) . The proportions of patients who received a transfusion during treatment were 6 % ( 95 % CI , 0 - 11 % ) for darbepoetin alfa and 16 % ( 95 % CI , 7%-25 % ) for epoetin alfa . Most patients ( 67 patients receiving darbepoetin alfa [ 93 % ] ; 61 patients receiving epoetin alfa [ 90 % ] ) exhibited a clinical ly meaningful target Hb level > or = 11 g/dL. No differences in safety were observed . CONCLUSION These results suggest that , in patients with breast cancer , darbepoetin alfa 200 microg every 2 weeks and epoetin alfa 40,000 U weekly result in comparable clinical outcomes for the treatment of chemotherapy-induced anemia This study compared the effects of early intervention with st and ard use of epoetin alfa on haemoglobin ( Hb ) levels and transfusion requirements in cancer patients receiving chemotherapy . Patients with Hb>10 and < or= 12 g/dL were r and omised 1:1 to epoetin alfa ( 40,000 IU , subcutaneously , once weekly ) , initiated within 7d of the start of the first on- study chemotherapy cycle ( defined as early intervention ) versus epoetin alfa when Hb < or= 10 g/dL ( defined as st and ard therapy ) . Increases in Hb values were significantly higher with early intervention compared to st and ard therapy from week 6 to 10 ( P < or= 0.05 ) and approached significance at week 15/16 ( P=0.0531 ) . Although the percentage of patients receiving blood transfusions was similar in both groups , the amount of blood transfused was almost twice as high in the st and ard epoetin alfa group ( n.s . ) . Early intervention with epoetin alfa was well tolerated and overall survival did not differ significantly between groups . Initiation of epoetin alfa at the onset of chemotherapy and Hb<12 g/dL improves Hb levels significantly versus st and ard therapy This is the first r and omized , open-label , multicenter trial design ed and powered to directly compare the hemoglobin ( Hb ) response to epoetin alfa ( EPO ) , 40,000 U once weekly ( QW ) , with that to darbepoetin alfa ( DARB ) , 200 microg every 2 weeks ( Q2W ) , in anemic patients with cancer receiving chemotherapy ( CT ) . Transfusion requirements , quality of life ( QOL ) , and safety also were evaluated . Adults with solid tumors scheduled to receive CT for > or = 12 weeks and with baseline Hb < or = 11 g/dl were r and omized to receive either EPO 40,000 U QW ( n = 178 ) or DARB 200 microg Q2W ( n = 180 ) s.c . for up to 16 weeks . Doses were increased for nonresponders ( Hb increase < 1 g/dl ) after 4 ( EPO ) or 6 ( DARB ) weeks , as per National Comprehensive Cancer Network guidelines , and were reduced for a rapid rise in Hb ( > 1.3 g/dl [ EPO ] or > 1.0 g/dl [ DARB ] within any 2-week period ) or for an Hb level > 13 g/dl . The proportion of patients achieving a > or = 1-g/dl Hb rise by week 5 , the primary end point , was significantly higher with EPO ( 47.0 % ) than with DARB ( 32.5 % ) , and EPO-treated patients achieved a > or = 1-g/dl Hb increase significantly earlier than those receiving DARB ( median , 35 days versus 46 days ) . The mean increase in Hb from baseline was significantly higher at weeks 5 , 9 , 13 , and the end of the study with EPO than with DARB . The number of units transfused per patient was significantly lower for the EPO group than for the DARB group . The proportions of patients requiring transfusions , mean QOL improvements , and tolerability profiles were similar in the two groups PURPOSE Recent reports suggest that cancer control may worsen if erythropoietin is administered . We investigated whether erythropoietin receptor expression on cancer cells may correlate with this unexpected finding . PATIENTS AND METHODS Cancer tissue from patients with advanced carcinoma of the head and neck ( T3 , T4 , or nodal involvement ) and scheduled for radiotherapy was assayed retrospectively for erythropoietin receptor expression by immunohistochemistry . Patients were anemic and r and omized to receive epoetin beta ( 300 U/kg ) or placebo under double-blind conditions , given three times weekly starting 10 to 14 days before and continuing throughout radiotherapy . We administered 60 Gy following complete resection or 64 Gy subsequent to microscopically incomplete resection ; 70 Gy were given following macroscopically incomplete resection or for definitive radiotherapy alone . We determined if the effect of epoetin beta on locoregional progression-free survival was correlated with the expression of erythropoietin receptors on cancer cells using a Cox proportional hazards regression model . RESULTS We studied 154 of 157 r and omly assigned patients ; 104 sample s were positive , and 50 were negative for receptor expression . Locoregional progression-free survival was substantially poorer if epoetin beta was administered to patients positive for receptor expression compared with placebo ( adjusted relative risk , 2.07 ; 95 % CI , 1.27 to 3.36 ; P < .01 ) . In contrast , epoetin beta did not impair outcome in receptor-negative patients ( adjusted relative risk , 0.94 ; 95 % CI , 0.47 to 1.90 ; P = .86 ) . The difference in treatment associated relative risks ( 2.07 v 0.94 ) was borderline statistically significant ( P = .08 ) . CONCLUSION Erythropoietin might adversely affect prognosis of head and neck cancer patients if cancer cells express erythropoietin receptors Darbepoetin alfa , an erythropoiesis-stimulating agent ( ESA ) , is used in cancer patients as a supportive care for anemia . For small-cell lung cancer ( SCLC ) , several studies have shown that the administration of ESAs does not affect survival but decreases the need for blood transfusions and improves the quality of life ( QOL ) of patients receiving chemotherapy . The present r and omized phase II study assessed the feasibility , efficacy , and safety of the administration of darbepoetin alfa to patients with SCLC receiving dose-dense ( every 2 weeks ) st and ard chemotherapy consisting of carboplatin plus etoposide , pegfilgrastim prophylactically . Seventy-four chemotherapy-naive patients with limited or extensive SCLC received combination chemotherapy for 6 cycles , and half of the patients additionally received darbepoetin to achieve a target hemoglobin concentration of 12 - 13 g/dL. The primary study outcome , progression-free survival , showed no difference between the 2 arms of the study . Among the secondary endpoints , objective response was similar in the presence and absence of darbepoetin ( best response rates = 75.0 % vs. 77.8 % ) . Likewise , 1-year survival rates were not different between the 2 treatment arms ( 40.1 % vs. 45.9 % ) . There were no significant differences in grade 3/4 toxicities . As expected , the need for blood transfusions differed significantly : 19.4 % of patients in the darbepoetin arm received transfusions versus 38.9 % in the control arm . Analysis of European Organization for Research and Treatment of Cancer quality of life question naire ( EORTC QLQ-C30 ) scales at different time points showed that the darbepoetin group 's QOL was significantly better for certain readouts and never significantly worse than that of the control group . Thus , the combination of darbepoetin alfa with dose-dense carboplatin plus etoposide was feasible and well tolerated . Addition of darbepoetin alfa to chemotherapy lowered the need for blood transfusions and did not affect measures of survival and objective response Abstract Background : In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy , epoetin-alfa effectively increased haemoglobin levels , reduced red blood cell transfusion requirements , and improved QOL . Although the study was not design ed or powered to evaluate survival , a survival trend was noted favouring epoetin-alfa compared with placebo ( median survival 17 vs 11 months [ p = 0.126 ] ) . Objectives : To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective . Methods : Patient data regarding transfusions , epoetin-alfa usage , chemotherapy treatment cycles , and adverse events were recorded , with survival follow-up for 12–36 months post- study . Stage IV breast cancer therapy costs were collected by surveying UK oncologists , and utilities for associated health states were from published sources . Costs were in British pounds and year 2000 values . Costs and benefits were jointly determined for the stage IV breast cancer subgroup ( n = 55 ) . Incremental cost-utility ratios ( ICURs ) were calculated assuming a 6 % annual discount rate for costs and a 1.5 % annual discount rate for benefits . Bootstrap simulations ( 10 000 iterations ) were conducted to account for uncertainty , and sensitivity analyses were conducted to establish robustness . Results : The ICUR for epoetin-alfa treatment was £ 8851 per QALY , with a 99 % probability of a positive net benefit in QALYs ( net benefit = 0.4805 years of perfect life ) and a 94 % probability of being acceptable using a threshold ICUR of £ 30 000/QALY . The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival . Conclusions : The available data suggest a high probability of favourable costutility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy . Additional studies are warranted BACKGROUND Epoetin-alpha initiated once weekly , followed by once-every-3-weeks maintenance , was effective and well tolerated for chemotherapy-induced anemia . This study evaluated a starting dose of epoetin-alpha 120,000 U once every 3 weeks for chemotherapy-induced anemia using early and late initiation regimens . METHODS Patients with baseline hemoglobin 11.0 - 12.0 g/dL were r and omly assigned to early intervention with immediate epoetin-alpha ( n = 68 ) or to st and ard intervention with epoetin-alpha when hemoglobin decreased to < 11 g/dL ( n = 68 ) . A third group of patients with baseline hemoglobin < 11 g/dL ( n = 50 ) were enrolled but not r and omized ; epoetin-alpha was initiated immediately . The primary endpoint was mean proportion of hemoglobin values within the target range ( 11.0 - 13.0 g/dL ) among r and omized patients . RESULTS The mean proportion of hemoglobin values in range through week 16 was 60 % in each r and omized group . Mean hemoglobin by week showed similar increases over the study . Blood transfusions were administered in 9 % , 8 % , and 24 % of patients in the early , st and ard , and nonr and omized groups . Mean epoetin-alpha doses were similar between treatment groups . Dose reductions and withholds were more common in the early intervention group . Adverse events ( eg , diarrhea , fatigue , nausea ) were consistent with the safety profile for epoetin-alpha . Clinical ly relevant thrombotic vascular events ( regardless of relationship to study treatment ) were reported for 9 % , 12 % , and 12 % of patients in the early , st and ard , and nonr and omized groups . CONCLUSIONS Early and st and ard intervention with epoetin-alpha , administered once every 3 weeks , increased and maintained hemoglobin levels within 11.0 - 13.0 g/dL in patients with chemotherapy-induced anemia Advanced cancer is often accompanied by anaemia , which may worsen with concomitant administration of chemotherapy . Serum erythropoietin ( EPO ) concentrations are lower in cancer patients than in patients with iron deficiency , suggesting that the anaemia observed in cancer patients is at least partially due to a relative deficiency of EPO . Consequently , we studied the effects of recombinant human erythropoietin ( r-HuEPO ) therapy in three population s of anaemic cancer patients : patients not receiving concomitant chemotherapy or radiotherapy ; patients receiving cyclic , non-cisplatin-containing chemotherapy , and patients receiving cyclic cisplatin-containing chemotherapy . Therapy with r-HuEPO was well tolerated ; it increased haematocrit levels and corrected anaemia , irrespective of concomitant chemotherapy or the type of chemotherapy administered . A dose of 150 U/kg r-HuEPO given subcutaneously 3 times weekly decreased transfusion requirements after the 1st month of therapy ; improved functional capacity was noted in patients who achieved a significant increase in haematocrit in response to r-HuEPO therapy PURPOSE The concomitant use of intravenous ( IV ) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial . This study was design ed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local st and ard practice ( oral iron or no iron ) . PATIENTS AND METHODS In this multicenter , r and omized , open-label , phase III study , 396 patients with nonmyeloid malignancies and hemoglobin ( Hb ) less than 11 g/dL received darbepoetin alpha 500 microg with ( n = 200 ) or without ( n = 196 ) IV iron once every 3 weeks ( Q3W ) for 16 weeks . RESULTS The hematopoietic response rate ( proportion of patients achieving Hb > or= 12 g/dL or Hb increase of > or= 2 g/dL from baseline ) was significantly higher in the IV iron group : 86 % versus 73 % in the st and ard practice group ( difference of 13 % [ 95 % CI , 3 % to 23 % ] ; P = .011 ) . Fewer RBC transfusions ( week 5 to the end of the treatment period ) occurred in the IV iron group : 9 % versus 20 % in the st and ard practice group ( difference of -11 % [ 95 % CI , -18 % to -3 % ] ; P = .005 ) . Both treatments were well tolerated with no notable differences in adverse events . Serious adverse events related to iron occurred in 3 % of patients in the IV iron group and were mostly gastrointestinal in nature . CONCLUSION Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated , result ing in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone PURPOSE To determine whether epoetin alfa reduces anemia-related fatigue , improves other aspects of health-related patient-recorded outcomes ( PROs ) , reduces the number of RBC transfusions , and has an impact on freedom from treatment failure ( FFTF ) and overall survival ( OS ) in patients with advanced-stage Hodgkin 's lymphoma ( HL ) . PATIENTS AND METHODS The prospect ively r and omized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy ( six to eight cycles of bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone [ BEACOPP ] ) in a double-blind , placebo-controlled setting . The study accrued 1,379 patients , of whom 1,328 were assessable for safety , 1,303 were assessable for clinical outcome , and 930 were assessable for PROs . RESULTS PROs were not different in patients receiving placebo or epoetin alfa , both after the end of chemotherapy and 6 months thereafter . There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS . There were also no differences in the numbers of deaths , progressions , relapses , and thromboembolic events . The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group ( P < .001 ) , with 27.4 % of patients needing no RBC transfusion in the placebo group compared with 36.7 % of patients in the epoetin alfa group ( P < .001 ) . CONCLUSION Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains |
2,335 | 15,542,965 | Glycemic control ( maintenance of glucose < 150 mg/dL ) is recommended .
The beneficial effect of glycemic control appears to be related control of glucose and not the administration of insulin .
Continuous hemofiltration offers easier management of fluid balance in hemodynamically unstable septic patients but in the absence of hemodynamic instability is equivalent to intermittent hemodialysis .
It is uncertain whether high-volume hemofiltration improves prognosis in sepsis . | OBJECTIVE In 2003 , critical care and infectious disease experts representing 11 international organizations developed management guidelines for adjunctive therapies in sepsis that would be of practical use for the bedside clinician , under the auspices of the Surviving Sepsis Campaign , an international effort to increase awareness and to improve outcome in severe sepsis .
The dialysis dose is important in sepsis-induced acute renal failure . | Objective To evaluate the effects of short-term , high-volume hemofiltration ( STHVH ) on hemodynamic and metabolic status and 28-day survival in patients with refractory septic shock . Design Prospect i ve , interventional . Setting Intensive care unit ( ICU ) , tertiary institution . Patients Twenty patients with intractable cardiocirculatory failure complicating septic shock , who had failed to respond to conventional therapy . Interventions STHVH , followed by conventional continuous venovenous hemofiltration . STHVH consisted of a 4-hr period during which 35 L of ultrafiltrate is removed and neutral fluid balance is maintained . Subsequent conventional continuous venovenous hemofiltration continued for at least 4 days . Measurements and Main Results Cardiac index , systemic vascular resistance , pulmonary vascular resistance , oxygen delivery , mixed venous oxygen saturation , arterial pH , and lactate were measured serially . Fluid and inotropic support were managed by protocol . Therapeutic endpoints were as follows during STHVH : a ) by 2 hrs , a ≥50 % increase in cardiac index ; b ) by 2 hrs , a ≥25 % increase in mixed venous saturation ; c ) by 4 hrs , an increase in arterial pH to > 7.3 ; d ) by 4 hrs , a ≥50 % reduction in epinephrine dose . Patients who attained all four goals ( 11 of 20 ) were considered hemodynamic “ responders ” ; patients who did not ( 9 of 20 ) were considered hemodynamic “ nonresponders . ” There were no differences in baseline hemodynamic , metabolic , and Acute Physiology and Chronic Health Evaluation and Simplified Acute Physiology Scores between responders and nonresponders . Survival to 28 days was better among responders ( 9 of 11 patients ) than among nonresponders ( 0 of 9 ) . Factors associated with survival were hemodynamic-metabolic response status , time interval from ICU admission to initiation of STHVH , and body weight . Conclusions These data suggest that STHVH may be of major therapeutic value in the treatment of intractable cardiocirculatory failure complicating septic shock . Early initiation of therapy and adequate dose may improve hemodynamic and metabolic responses and 28-day survival STUDY OBJECTIVE To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis . DESIGN Prospect i ve , r and omized , blinded , crossover study . Each patient sequentially received sodium bicarbonate and equimolar sodium chloride . The order of the infusions was r and omized . SETTING Intensive care unit of a tertiary care hospital . PATIENTS Fourteen patients who had metabolic acidosis ( bicarbonate less than 17 mmol/L and base excess less than -10 ) and increased arterial lactate ( mean , 7.8 mmol/L ) . All had pulmonary artery catheters and 13 were receiving catecholamines . MEASUREMENTS AND MAIN RESULTS Sodium bicarbonate ( 2 mmol/kg body weight over 15 minutes ) increased arterial pH ( 7.22 to 7.36 , P less than 0.001 ) , serum bicarbonate ( 12 to 18 mmol/L , P less than 0.001 ) , and partial pressure of CO2 in arterial blood ( PaCO2 ) ( 35 to 40 mm Hg , P less than 0.001 ) and decreased plasma ionized calcium ( 0.95 to 0.87 mmol/L , P less than 0.001 ) . Sodium bicarbonate and sodium chloride both transiently increased pulmonary capillary wedge pressure ( 15 to 17 mm Hg , and 14 to 17 mm Hg , P less than 0.001 ) and cardiac output ( 18 % and 16 % , P less than 0.01 ) . The mean arterial pressure was unchanged . Hemodynamic responses to sodium bicarbonate and sodium chloride were the same . These data have more than 90 % power of detecting a 0.5 L/min ( 7 % ) change in mean cardiac output after administration of sodium bicarbonate compared with that after sodium chloride . Even the 7 most acidemic patients ( mean pH , 7.13 ; range , 6.90 to 7.20 ) had no significant hemodynamic changes after either infusion . CONCLUSIONS Correction of acidemia using sodium bicarbonate does not improve hemodynamics in critically ill patients who have metabolic acidosis and increased blood lactate or the cardiovascular response to infused catecholamines in these patients . Sodium bicarbonate decreases plasma ionized calcium and increases PaCO2 BACKGROUND Acute renal failure ( ARF ) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50 to 80 % . The worldwide st and ard for renal replacement therapy is intermittent hemodialysis ( IHD ) . Continuous hemodialysis and hemofiltration techniques have recently emerged as alternative modalities . These two therapies have not been directly compared . METHODS A multicenter , r and omized , controlled trial was conducted comparing two dialysis modalities ( IHD vs. continuous hemodiafiltration ) for the treatment of ARF in the intensive care unit ( ICU ) . One hundred sixty-six patients were r and omized . Principal outcome measures were ICU and hospital mortality , length of stay , and recovery of renal function . RESULTS Using intention-to-treat analysis , the overall ICU and in-hospital mortalities were 50.6 and 56.6 % , respectively . Continuous therapy was associated with an increase in ICU ( 59.5 vs. 41.5 % , P < 0.02 ) and in-hospital ( 65.5 vs. 47.6 % , P < 0.02 ) mortality relative to intermittent dialysis . Median ICU length of stay from the time of nephrology consultation was 16.5 days , and complete recovery of renal function was observed in 34.9 % of patients , with no significant group differences . Despite r and omization , there were significant differences between the groups in several covariates independently associated with mortality , including gender , hepatic failure , APACHE II and III scores , and the number of failed organ systems , in each instance biased in favor of the intermittent dialysis group . Using logistic regression to adjust for the imbalances in group assignment , the odds of death associated with continuous therapy was 1.3 ( 95 % CI , 0.6 to 2.7 , P = NS ) . A detailed investigation of the r and omization process failed to explain the marked differences in patient assignment . CONCLUSIONS A r and omized controlled trial of alternative dialysis modalities in ARF is feasible . Despite the potential advantages of continuous techniques , this study provides no evidence of a survival benefit of continuous hemodiafiltration compared with IHD . This study did not control for other major clinical decisions or other supportive management strategies that are widely variable ( for example , nutrition support , hemodynamic support , timing of initiation , and dose of dialysis ) and might material ly influence outcomes in ARF . St and ardization of several aspects of care or extremely large sample sizes will be required to answer optimally the questions originally posed by this investigation Objectives Maintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients . Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits . Design A prospect i ve , r and omized , controlled trial . Setting A 56-bed predominantly surgical intensive care unit in a tertiary teaching hospital Patients and InterventionA total of 1,548 patients were r and omly assigned to either strict normalization of blood glucose ( 80–110 mg/dL ) with insulin infusion or the conventional approach , in which insulin is only given to maintain blood glucose levels at 180–200 mg/dL. Measurements and Main Results It was feasible and safe to achieve and maintain blood glucose levels at < 110 mg/dL by using a titration algorithm . Stepwise linear regression analysis identified body mass index , history of diabetes , reason for intensive care unit admission , at-admission hyperglycemia , caloric intake , and time in intensive care unit as independent determinants of insulin requirements , together explaining 36 % of its variation . With nutritional intake increasing from a mean of 550 to 1600 calories/day during the first 7 days of intensive care , normoglycemia was reached within 24 hrs , with a mean daily insulin dose of 77 IU and maintained with 94 IU on day 7 . Insulin requirements were highest and most variable during the first 6 hrs of intensive care ( mean , 7 IU/hr ; 10 % of patients required > 20 IU/hr ) . Between day 7 and 12 , insulin requirements decreased by 40 % on stable caloric intake . Brief , clinical ly harmless hypoglycemia occurred in 5.2 % of intensive insulin-treated patients on median day 6 ( 2–14 ) vs. 0.8 % of conventionally treated patients on day 11 ( 2–10 ) . The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding . Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality ( p < .0001 ) , critical illness polyneuropathy ( p < .0001 ) , bacteremia ( p = .02 ) , and inflammation ( p = .0006 ) but not to prevention of acute renal failure , for which the insulin dose was an independent determinant ( p = .03 ) . As compared with normoglycemia , an intermediate blood glucose level ( 110–150 mg/dL ) was associated with worse outcome . Conclusion Normoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines . Metabolic control , as reflected by normoglycemia , rather than the infused insulin dose per se , was related to the beneficial effects of intensive insulin therapy BACKGROUND This study was design ed to determine the consequences of acute hyperglycemia on the immune function of peripheral neutrophils , peritoneal macrophages , and alveolar macrophages in nondiabetic rats . METHODS The animals were r and omly divided into nonsurgical ( normal ) and surgical groups . The postoperative rats were further divided into normoglycemic ( control ) and hyperglycemic ( glucose ) groups . The hyperglycemic condition was maintained by constant infusion of glucose to raise plasma glucose concentration to 300 mg/dL for 3 hours . The immune cells were then harvested to determine their phagocytic and oxidative capacities via flow cytometry . RESULTS The results showed that hyperglycemia significantly decreased the respiratory burst of alveolar macrophages ( p < .05 ) . In contrast , hyperglycemia enhanced phagocytosis in these cells ( p < .002 ) . There was a significant activation of the respiratory burst in peripheral neutrophils by surgery ( p < .002 ) , but no effect of hyperglycemia . CONCLUSIONS We conclude that hyperglycemia itself can influence immune function in some phagocytic cells , which may be an important factor in postsurgical infection Objective To study the effect of early and continuous venovenous hemofiltration ( CVVH ) on the plasma concentrations of several humoral mediators of inflammation and subsequent organ dysfunction in septic patients . Design R and omized , controlled trial . Setting Intensive care unit of a tertiary hospital . Patients Twenty-four patients with early septic shock or septic organ dysfunction . Interventions R and om allocation to receive 48 hrs of isovolemic CVVH at 2 L/hr of fluid exchange or no hemofiltration . Measurements and Main Results We measured the plasma concentrations of complement fractions C3a and C5a , interleukins 6 , 8 , and 10 , and tumor necrosis factor & agr ; at baseline and 2 , 24 , 26 , 48 , and 72 hrs . A multiple organ dysfunction score ( MODS ) was calculated daily for each patient until death or discharge from the intensive care unit . The concentrations of most mediators decreased between baseline and 72 hrs . Some significant falls in concentration could be identified between specific time points , but CVVH was not associated with an overall reduction in any plasma cytokine concentrations . There was also no difference between the mean cumulative MODS for control survivors ( 43.3 ± 19.7 ) and CVVH survivors ( 33.2 ± 19.0;p = .30 ) , and no difference between the average MODS calculated for all controls ( 4.1 ± 1.9 ) and all CVVH subjects ( 3.3 ± 1.7;p = .26 ) . CVVH did not improve oxygenation , lower the platelet count , or reduce the duration of vasopressor support and mechanical ventilation . Conclusions Early use of CVVH at 2 L/hr did not reduce the circulating concentrations of several cytokines and anaphylatoxins associated with septic shock , or the organ dysfunction that followed severe sepsis . CVVH using current technology can not be recommended as an adjunct to the treatment of septic shock unless severe acute renal failure is present Lactic acidosis decreases left ventricular contractility , but whether bicarbonate increases left ventricular contractility during lactic acidosis in vivo is controversial . Therefore , we measured hemodynamics and left ventricular mechanics before and after bicarbonate administration during L-lactic acid infusion in 15 anesthetized pigs . The pigs were beta-blocked and atrially paced to minimize indirect effects of acidosis on contractility . We measured mean arterial pressure , left ventricular end-diastolic pressure , thermodilution cardiac output , left ventricular pressure ( Miller catheter ) , and left ventricular volume ( three orthogonal pairs of ultrasonic crystals ) . Left ventricular contractility was assessed primarily using the slope ( Emax ) of the end-systolic pressure-volume relationship . While PCO2 was kept constant , 0.2 M L-lactic acid was infused , which reduced arterial pH to 7.05 + /- 0.06 . Animals were then r and omized to receive either 1 M NaHCO3 ( n = 8) , which increased pH to 7.45 + /- 0.11 , or an equivalent amount of 1 M NaCl ( n = 7 ) . Bicarbonate decreased mean arterial pressure ( 105 + /- 20 to 95 + /- 39 mm Hg , p < 0.05 ) but did not increase cardiac output . These effects were not significantly different from the effects of saline . Bicarbonate did not significantly increase Emax ( 4.2 + /- 0.8 to 4.9 + /- 0.8 mm Hg/ml ) and was indistinguishable from saline ( 5.0 + /- 0.7 to 5.2 + /- 0.7 mm Hg/ml ) . We conclude that bicarbonate infusion does not directly increase left ventricular contractility during lactic acidemia in pigs within this pH range Abstract Objectives . To describe the current practice of hemodialysis in acute renal failure ( ARF ) and to estimate the impact of hemodialysis modality on patient outcome . Design . Prospect i ve multicenter observational study conducted from March 1996 to May 1997 . Setting . The 28 multidisciplinary ICUs in the Rhône-Alpes region in France . Patients . The 587 patients who required hemodialysis . Measurements and results . Patients were followed until hospital discharge . Among the 587 patients 354 received continuous ( CRRT ) and 233 intermittent ( IRRT ) renal replacement therapy as first choice . CRRT patients had a higher number of organ dysfunctions on admission and at the time of ARF and higher SAPS II at time of ARF . Mortality was 79 % in the CRRT group and 59 % in the IRRT group . Logistic regression analysis showed decreased patient survival to be associated with SAPS II on admission , oliguria , admission from hospital or emergency room , number of days between admission and ARF , cardiac dysfunction at time of ARF , and ischemic ARF . No underlying disease or nonfatal disease , and absence of hepatic dysfunction were associated with an increase in patient survival . The type of renal replacement therapy was not significantly associated with outcome . Conclusions . Renal replacement therapy mode was not found to have any prognostic value . R and omized controlled trials should be undertaken to assess this important question The effects of Carbicarb , sodium bicarbonate , and sodium chloride on arterial blood gases , lactate concentrations , hemodynamics , and myocardial intracellular pH were compared in hypoxic lactic acidosis with controlled carbon dioxide elimination . Twenty-one young mongrel dogs were anesthetized , mechanically ventilated , and r and omly allocated into one of three treatment groups . After hypoxic lactic acidosis was induced and maintained , 2.5 mEq/kg of one of the agents was infused over 30 min . Arterial blood gases , pH , lactate concentrations , and hemodynamic variables were measured immediately prior to the infusion of the agent and 30 min after the infusion was completed . With sodium bicarbonate administration , there was a significant increase in arterial PCO2 as compared to both Carbicarb or sodium chloride administration . With Carbicarb administration , there was a significant increase in arterial pH , base excess , and cardiac index , without a significant increase in arterial lactate concentration as compared to sodium bicarbonate or sodium chloride administration . Stroke volume index was also increased significantly with decreased heart rate . The data suggest that Carbicarb administration in hypoxic lactic acidosis improved hemodynamics compared with sodium bicarbonate or sodium chloride administration . The increased stroke volume and cardiac contractility appear to be due to improved myocardial intracellular Objective To determine whether correction of acidemia using bicarbonate improves hemodynamic variables and tissue oxygenation in patients with lactic acidosis . Design Prospect i ve , r and omized , blinded , cross over study . Each patient sequentially received sodium bicarbonate and sodium chloride . The order of the infusions was r and omized . Patients Ten patients with metabolic acidosis , increased arterial plasma lactate concentrations ( > 2.45 mmol/L ) , and no severe renal failure ( creatinine < 250 μmol/L [ < 2.3 mg/dL ] ) . MethodS odium bicarbonate ( 1 mmol/kg body weight ) or equal volume of sodium chloride was injected iv at the beginning of two successive 1-hr study periods . Period order was r and omized . Arterial and venous blood gas measurements , plasma electrolytes ( sodium , potassium , chloride ) , osmolality and lactate , 2,3-diphosphoglycerate ( DPG ) , and oxygen hemoglobin affinity , hemodynamic variables , oxygen delivery , and oxygen consumption measurements were obtained before and repeatedly during the 1-hr period after the injection of bicarbonate or sodium chloride . Measurements and Main Results Sodium bicarbonate administration increased arterial and venous pH , serum bicarbonate , and the partial pressure of CO2 in arterial and venous blood . Hemodynamic responses to sodium bicarbonate and sodium chloride were similar . Tissue oxygenation ( as estimated by oxygen delivery , oxygen consumption , oxygen extraction ratio , and transcutaneous oxygen pressure ) was not modified . No changes in serum sodium concentration , osmolality , arterial and venous lactate , red cell 2,3-DPG levels , or hemoglobin affinity for oxygen were observed . Conclusion Administration of sodium bicarbonate did not improve hemodynamic variables in patients with lactic acidosis , but did not worsen tissue oxygenation Objective To determine whether hemofiltration ( HF ) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis . Design Prospect i ve observation study . Setting Surgical intensive care unit of a university hospital . Patients 16 patients with severe sepsis . Interventions Continuous zero-balanced HF without dialysis ( ultrafiltrate rate 21/h ) was performed in addition to pulmonary artery catheterization , arterial cannulation , and st and ard intensive care treatment . Measurements and main results Plasma and ultrafiltrate concentrations of cytokines ( the interleukins IL-1β , IL-6 , IL-8 , and tumor necrosis factor α ) and of complement components ( C3adesArg , C5adesArg ) were measured after starting HF ( t0 ) and 4 h ( t4 ) and 12 h later ( t12 ) . Hemodynamic variables including mean arterial pressure ( MAP ) , mean central venous pressure , mean pulmonary artery pressure , pulmonary capillary wedge pressure , and cardiac output were serially determined . During HF , cytokine plasma concentrations remained constant . However , C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF ( C3adesArg : t0=676.9±99.7 ng/ml vs t12=467.8±71,p<0.01 ; C5adesArg : 26.6±4.7 ng/ml vs 17.6±6.2,p<0.01 ) . HF result ed in a significant increase over time in systemic vascular resistance ( SVR ) and MAP ( SVR at t0 : 669±85 dyne·s/cm5 vs SVR at t12 : 864±75,p<0.01 ; MAP at t0 : 69.9±3.5 mmHg vs MAP at t12 : 82.2±3.7,p<0.01 ) . Conclusions HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis . There was also a significant rise in SVR and MAP during high volume HF . Therefore , HF may represent a new modality for removal of anaphylatoxins and may , thereby , deserve clinical testing in patients with severe sepsis BACKGROUND Intermittent hemodialysis is widely used as renal-replacement therapy in patients with acute renal failure , but an adequate dose has not been defined . We performed a prospect i ve study to determine the effect of daily intermittent hemodialysis , as compared with conventional ( alternate-day ) intermittent hemodialysis , on survival among patients with acute renal failure . METHODS A total of 160 patients with acute renal failure were assigned to receive daily or conventional intermittent hemodialysis . Survival was the primary end point of the study . The duration of acute renal failure and the frequency of therapy-related complications were secondary end points . RESULTS The two study groups were similar with respect to age , sex , cause and severity of acute renal failure , medical or surgical intensive care setting , and the score on the Acute Physiology , Age , and Chronic Health Evaluation . Daily hemodialysis result ed in better control of uremia , fewer hypotensive episodes during hemodialysis , and more rapid resolution of acute renal failure ( mean [ + /-SD ] , 9+/-2 vs. 16+/-6 days ; P=0.001 ) than did conventional hemodialysis . The mortality rate , according to the intention-to-treat analysis , was 28 percent for daily dialysis and 46 percent for alternate-day dialysis ( P=0.01 ) . In a multiple regression analysis , less frequent hemodialysis ( on alternate days , as opposed to daily ) was an independent risk factor for death . CONCLUSIONS The high mortality rate among critically ill patients with acute renal failure who require renal-replacement therapy is related to both coexisting conditions and uremic damage to other organ systems . Intensive hemodialysis reduces mortality without increasing hemodynamically induced morbidity Objective To study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure . The primary end points were mortality at 28 days and recovery of renal function . Design A r and omized , controlled , two-center study . Setting The closed-format multidisciplinary intensive care units of a university hospital ( 30 beds ) and a teaching hospital ( 18 beds ) . Patients and Interventions A total of 106 ventilated severely ill patients who were oliguric despite massive fluid resuscitation , inotropic support , and high-dose intravenous diuretics were r and omized into three groups . Thirty-five patients were treated with early high-volume hemofiltration ( 72–96 L per 24 hrs ) , 35 patients with early low-volume hemofiltration ( 24–36 L per 24 hrs ) , and 36 patients with late low-volume hemofiltration ( 24–36 L per 24 hrs ) . Results Median ultrafiltrate rate was 48.2 ( 42.3–58.7 ) mL·kg−1·hr−1 in early high-volume hemofiltration , 20.1 ( 17.5–22.0 ) mL·kg−1·hr−1 in early low-volume hemofiltration , and 19.0 ( 16.6–21.1 ) mL·kg−1·hr−1 in late low-volume hemofiltration . Survival at day 28 was 74.3 % in early high-volume hemofiltration , 68.8 % in early low-volume hemofiltration , and 75.0 % in late low-volume hemofiltration ( p = .80 ) . On average , hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group . All hospital survivors had recovery of renal function at hospital discharge , except for one patient in the early low-volume hemofiltration group . Median duration of renal failure in hospital survivors was 4.3 ( 1.4–7.8 ) days in early high-volume hemofiltration , 3.2 ( 2.4–5.4 ) days in early low-volume hemofiltration , and 5.6 ( 3.1–8.5 ) days in late low-volume hemofiltration ( p = .25 ) . Conclusions In the present study of critically ill patients with oliguric acute renal failure , survival at 28 days and recovery of renal function were not improved using high ultrafiltrate volumes or early initiation of hemofiltration Objectives Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality . Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown . The aim of this study was to analyze severity of illness and mortality in a group of critically ill patients with acute renal failure requiring renal replacement therapy in a number of Austrian intensive care units . Design Prospect i ve , multicenter cohort study . Patients and Setting A total of 17,126 patients admitted consecutively to 30 medical , surgical , and mixed intensive care units in Austria over a period of 2 yrs . Measurements and Main Results Analyzed data included admission data , Simplified Acute Physiology Score , Logistic Organ Dysfunction system , Simplified Therapeutic Intervention Scoring System , length of intensive care unit stay , intensive care unit mortality , and hospital mortality . Of the admitted patients , 4.9 % ( n = 839 ) underwent renal replacement therapy because of acute renal failure ( renal replacement therapy patients ) . These patients had a significantly higher hospital mortality ( 62.8 % vs. 15.6 % , p < .001 ) , which remained significantly higher even when renal replacement therapy patients were matched with control subjects for age , severity of illness , and treatment center . Since univariate analysis demonstrated further intensity of treatment to be an additional predictor for outcome , a multivariate model including therapeutic interventions was developed . Five interventions were associated with nonsurvival ( mechanical ventilation , single vasoactive medication , multiple vasoactive medication , cardiopulmonary resuscitation , and treatment of complicated metabolic acidosis/alkalosis ) . In contrast , the use of enteral nutrition predicted a favorable outcome . Conclusions The results of our study suggest that acute renal failure in patients undergoing renal replacement therapy presents an excess risk of in-hospital death . This increased risk can not be explained solely by a more pronounced severity of illness . Our results provide strong evidence that acute renal failure presents a specific and independent risk factor for poor prognosis OBJECTIVE To evaluate the effect of continuous venovenous hemofiltration with dialysis on lactate elimination by critically ill patients . DESIGN Prospect i ve , clinical study . SETTING Surgical intensive care unit of a university hospital . PATIENTS Ten critically ill patients with acute renal failure and stable blood lactate concentrations . INTERVENTIONS Two-stage investigation : a ) measurement of lactate concentrations in sample s of serum and ultradiafiltrate from patients receiving continuous venovenous hemofiltration with dialysis to calculate lactate clearance by the hemofilter ; b ) evaluation of total plasma lactate clearance by infusing sodium L-lactate ( 1 mmol/kg of body weight ) over 15 mins . MEASUREMENTS AND MAIN RESULTS Arterial lactate concentration was determined before , during , and after the infusion . Lactate elimination variables were calculated from the plasma curve using model-independent and model-dependent estimates ( by software ) . At the end of the infusion , median blood lactate concentration increased from 1.4 mmol/L ( range 0.8 to 2.6 ) to 4.8 mmol/L ( range 2.4 to 5.7 ) and returned to 1.6 mmol/L ( range 0.9 to 3.4 ) 60 mins later . The median total plasma lactate clearance was 1379 mL/min ( range 753.7 to 1880.7 ) and the median filter lactate clearance was 24.2 mL/min ( range 7.1 to 35.6 ) . Thus , filter lactate clearance accounted for < 3 % of total lactate clearance . CONCLUSIONS Continuous venovenous hemofiltration with dialysis can not mask lactate overproduction , and its blood concentration remains a reliable marker of tissue oxygenation in patients receiving this renal replacement technique Data acquired prospect ively from 134 patients with acute renal failure requiring dialysis in a medical intensive care unit ( ICU ) were analysed in order to derive indicators predicting ICU-survival Mortality in the ICU was 56.7 % . Linear discriminant analysis correctly predicted outcome in 79.9 % at the start of dialysis , and 84.7 % at 48 h after the first dialysis . The most important predictive variables were mechanical ventilation and low blood pressure . On the other h and , the total correct classification rates achieved by a st and ardised system for scoring ICU- patients ( APACHE II ) did not exceed 58.2 % . It is concluded that outcome prediction by APACHE II and even by the discriminant functions is too inaccurate to become the basis for clinical decisions either concerning the initiation or the continuation of dialysis treatment in ARF A prospect i ve study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis . Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg L-lactate over 15 min . The patients were divided in two groups depending on their blood lactate : < or = 1.5 mmol/L ( n = 20 , lactate = 1.2+/-0.2 mmol/L ) or > or = 2 mmol/L ( n = 10 , lactate = 2.6+/-0.6 mmol/L ) . The hyperlactatemic patients had a lower lactate clearance ( 473+/-102 ml/kg/h ) than those with normal blood lactate ( 1,002+/-284 ml/kg/h , p < 0.001 ) , whereas lactate production in the two groups was similar ( 1,194+/-230 and 1,181+/-325 micromol/kg/h , p = 0.90 ) . A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance ( r2 = 0.73 , p < 0.001 ) but not to lactate production ( r2 = 0.03 , p = 0.29 ) . We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization Abstract . Objective : To evaluate whether high volume haemofiltration improves haemodynamics and affects serum cytokine and complement concentrations in human septic shock . Design and setting : R and omized cross-over clinical trial in a tertiary intensive care unit . Patients : Eleven patients with septic shock and multi-organ failure . Interventions : Patients were assigned to either 8 h of high-volume haemofiltration ( HVHF ; 6 l/h ) or 8 h of st and ard continuous veno-venous haemofiltration ( CVVH ; 1 l/h ) in r and om order . Measurements and main results : We measured changes in haemodynamic variables , dose of norepinephrine required to maintain a mean arterial pressure greater than 70 mmHg and plasma concentrations of complement anaphylatoxins and several cytokines . An 8-h period of HVHF was associated with a greater reduction in norepinephrine requirements than a similar period of CVVH ( median reduction : 10.5 vs. 1.0 µg/min ; p=0.01 ; median percentage reduction : 68 vs. 7 % ; p=0.02 ) . Both therapies were associated with a temporary reduction ( p<0.01 ) in the plasma concentration of C3a , C5a , and interleukin 10 within 2 h of initiation . HVHF was associated with a greater reduction in the area under the curve for C3a and C5a ( p<0.01 ) . The concentration of the measured soluble mediators in the ultrafiltrate was negligible . Conclusions : HVHF decreases vasopressor requirements in human septic shock and affects anaphylatoxin levels differently than st and ard An open , prospect i ve evaluation of the effects of dichloroacetate on morbidity and survival time was done in 29 pediatric and adult patients with lactic acidosis . Dichloroacetate was administered intravenously over 30 minutes as two 50 mg/kg body weight doses separated by 2 hours . Five patients underwent retreatment with two additional drug doses and were considered new cases when analyzing for treatment response . Survival , however , was determined from the time of initial entry into the study . Patients were considered to respond to treatment if arterial lactate concentration decreased at least 20 % from the pretreatment level within 6 hours of beginning the first dichloroacetate infusion . Using this criterion , 26 cases responded to therapy with dichloroacetate . For all cases , patients ' mean arterial lactate concentration decreased 52 % ( P = 0.0009 ) , arterial bicarbonate concentration increased 35 % ( P = 0.0003 ) , and arterial pH increased ( P = 0.024 ) to normal , defined as the range 7.35 to 7.45 . Among responders , however , arterial lactate concentration decreased 74 % ( P = 0.0001 ) , arterial bicarbonate level increased 47 % ( P = 0.0001 ) , and arterial pH increased ( P = 0.0004 ) to the normal range . Median survival time among responders was 60 hours , compared to 26 hours among nonresponders ( P less than 0.001 ) . There was no evidence of toxicity to dichloroacetate It is unknown whether continuous renal replacement techniques result in diminished morbidity and mortality when compared to conventional dialytic techniques . To investigate this issue a previously described , retrospectively studied group of critically ill patients with severe acute renal failure treated by conventional dialysis ( CD ) was compared to a prospect ively studied group of similar patients treated by acute continuous hemodiafiltration ( ACHD ) . A combined retrospective and prospect i ve clinical and laboratory investigation was carried out for 234 consecutive critically ill patients with severe acute renal failure in the intensive care unit of a tertiary institution . Biochemical , clinical and outcome data in all patients treated by conventional dialytic techniques ( intermittent hemodialysis and /or peritoneal dialysis ) during a 5-year period were retrospectively analyzed , and a prospect i ve analysis of the same biochemical , clinical and outcome data in all patients treated by acute continuous hemodiafiltration was done over a similar time span , with statistical comparison of findings . One hundred and fifty patients were treated by ACHD and 84 by CD . ACHD patients were more severely ill ( mean APACHE II score : 28.2 vs. 25.8 ; p < 0.01 ) and older ( mean age : 59.9 vs. 55.5 years ; p < 0.01 ) . There were no significant differences in the incidence of sepsis , bacteremia and need for mechanical ventilation . ACHD result ed in better control of uremia ( mean steady-state plasma urea level : 20.1 vs. 31.7 mmol/l ; p < 0.001 ) and hyperphosphatemia ( mean serum phosphate : 1.26 vs. 1.95 mmol/l ) after 24 h of initiation of therapy . It also allowed the administration of full nutritional support in a significantly greater percentage of patients ( 91.3 vs. 64.8 % ; p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS |
2,336 | 28,040,292 | There was no evidence of a difference in effect when comparing RT and AT .
Shorter duration CT was superior to shorter duration AT for improving peak oxygen uptake and muscular strength ( low quality evidence ) while longer duration CT was only superior to longer duration AT in improving muscular strength ( moderate quality evidence ) .
CT is more beneficial than AT alone for improving physical function .
Shorter duration interventions that include resistance training might allow patients to return to their normal activities of daily living earlier | BACKGROUND Resistance training has demonstrated efficacy in cardiac rehabilitation programs , but the optimal prescription of resistance training is unknown .
This systematic review with meta- analysis compared the effectiveness of cardiac rehabilitation consisting of resistance training either alone ( RT ) or in combination with aerobic training ( CT ) with aerobic training only ( AT ) on outcomes of physical function .
Further , resistance training intensity and intervention duration were examined to identify if these factors moderate efficacy . | Increased fat mass , particularly abdominal fat mass , is associated with poor metabolic profiles and an increase in cardiovascular risk factors . The purpose of this study was to evaluate the effect of a 1-year combined aerobic and strength training regimen , compared to aerobic training only , on body composition in patients with coronary artery disease ( CAD ) . Thirty-six males with CAD were assigned to 3 groups : 13 to weight training plus aerobic training ( combined training group [ CT ] ) , 13 to aerobic training only ( aerobic training group [ AT ] ) , and 10 to a control group ( no exercise [ CG ] ) . Body composition was determined by dual-energy x-ray absorptiometry ( DEXA ) . Differences were observed between groups at the end of the study , controlling for prevalues . The total and trunk percent fat mass ( % FM ) were lower in CT compared with AT and CG ( P<.05 ) . The total % FM in AT was significantly ( P<.05 ) lower than in CG , but the % FM of the trunk did not differ between the 2 groups . Fat-free mass ( FFM ) was significantly higher in CT than in AT and CG ( P<.05 ) . The results suggest that a long-term CT program is more effective than an AT program alone in producing changes in body composition . The percentage changes in total and trunk fat mass were higher in CT ( -11 % and -12 % , respectively ) than in AT ( -2.4 % and -0.7 % , respectively ) . Future studies need to investigate the specific health effects of trunkal fat mass loss in patients with CAD A prospect i ve , r and omized study evaluated the feasibility , safety , and efficacy of upper body circuit weight training ( CWT ) in 25 stable male cardiac patients entering the initial out-of-hospital phase of cardiac rehabilitation . Both groups performed 30 minutes of aerobic exercise only for 6 weeks . The aerobic exercise group ( N = 13 ) continued this regimen for 6 more weeks , during which time the CWT group ( N = 12 ) performed 15 minutes of aerobic exercise followed by CWT ( two loops , eight upper body exercises ) . The only adverse response was in one CWT patient in whom restenosis developed . Peak heart rate during aerobic exercise and CWT was similar , but peak systolic blood pressure during aerobic exercise was significantly greater than during CWT . Peak rate pressure product during aerobic exercise and CWT was similar . Treadmill time increased significantly in both groups . Upper body strength ( cumulative pounds lifted ) increased significantly only in the CWT group . A coordinated program of CWT and aerobic exercise can be performed safely in stable cardiac patients during phase 2 cardiac rehabilitation , result ing in improved upper body strength and aerobic capacity PURPOSE We evaluated the value of resistance training on measures of physical performance in disabled older women with coronary heart disease ( CHD ) . METHODS The study intervention consisted of a 6-month program of resistance training in a r and omized controlled trial format . Training intensity was at 80 % of the single-repetition maximal lift . Control patients performed light yoga and breathing exercises . Study participants included 42 women with CHD , all > or= 65 yr of age and community dwelling . Subjects were screened by question naire to have low self-reported physical function . The primary study measurements related to the performance of 16 household activities of the Continuous Scale Physical Functional Performance test ( CSPFP ) . These ranged from dressing , to kitchen and cleaning activities , to carrying groceries and walking onto a bus with luggage , and a 6-min walk . Activities were measured in time to complete a task , weight carried during a task , or distance walked . Other measures included body composition , measures of aerobic fitness and strength , and question naire-based measures of physical function and depression score . RESULTS Study groups were similar at baseline by age , aerobic capacity , strength , body composition , and in performing the CSPFP . After conditioning , 13 of 16 measured activities were performed more rapidly , or with increased weight carried , compared with the control group ( all P < 0.05 ) . Maximal power for activities that involved weight-bearing over a distance , increased by 40 % ( P < 0.05 ) . CONCLUSIONS Disabled older women with CHD who participate in an intense resistance-training program improve physical capacity over a wide range of household physical activities . Benefits extend beyond strength-related activities , as endurance , balance , coordination , and flexibility all improved . Strength training should be considered an important component in the rehabilitation of older women with CHD In the context of sedentary middle-aged adults , the present study examined the relationships among domain-specific and global levels of self-esteem over the course of a 20-week exercise program . Additionally , the roles played by physical fitness , body composition , self-efficacy , and exercise participation as possible contributors to changes in physical self-worth were examined . Significant improvements in self-esteem at all levels were discovered with global esteem , physical self-worth , and perceptions of physical condition and attractive body increasing . Tests of the hierarchical structure of self-esteem showed greater improvements in physical condition and physical self-worth than global esteem and the relationships between global esteem and subdomain levels were shown to be mediated by physical self-worth . Hierarchical regression analyses showed changes in ratings of importance to have little impact on changes in physical self-worth . Both changes in efficacy and aerobic capacity were demonstrated to account for modest but significant variation in physical self-esteem . Results are discussed in terms of contemporary models of self-esteem , potential mediators of exercise effects on esteem , and the need to measure the constructs of interest appropriately BACKGROUND Many activities of daily living require significant amounts of muscular strength . Time lines for current strength training guidelines preclude many myocardial infa rct ion patients from receiving strength training as part of their cardiac rehabilitation program . This study was design ed to examine the effectiveness and safety of low-to-moderate level strength training in patients early after myocardial infa rct ion . METHODS Fifty-seven low-risk men ( < 61 years of age , 6 - 16 weeks post-infa rct ion ) were r and omly assigned to a control group or one of three treatment groups . All groups trained aerobically , three times per week for 12 weeks . The three treatment groups performed additional strength exercises on each training day of the last 10 weeks . These groups differed in their strength training stimulus with Group 20 performing 20 reps of 20 % of 1 repetition maximum ( 1 RM ) , Group 40 performing 10 repetitions of 40 % of 1 RM , and Group 60 performing 7 repetitions of 60 % of 1 RM . RESULTS Maximal strength remained unchanged in the control group ( + 0.5 % ) , but increased in Groups 20 , 40 , and 60 by + 10.5 % , + 11.9 % , and + 13.5 % , respectively . The increases in strength in the treatment groups were all significantly different ( P < .001 ) from the results of the control group , but were not significantly different from each other . For the three treatment groups , 30 of 42 subjects had one or more cardiovascular complication ( arrhythmias , angina , ischemia , hypertension , hypotension ) during the aerobic exercises as compared to only 1 subject with complications during the resistive exercises ( P < .01 ) . CONCLUSIONS In selected patients , low-to-moderate intensity strength training performed early after infa rct ion is effective and may have lower rates of cardiovascular problems than aerobic exercise BACKGROUND Muscle power ( force x velocity ) recedes at a faster rate than strength with age and may also be a stronger predictor of fall risk and functional decline . The optimal training paradigm for improving muscle power in older adults is not known , although some literature suggests high velocity , low load training is optimal in young adults . METHODS One hundred twelve healthy older adults ( 69 + /- 6 years ) were r and omly assigned to either explosive resistance training at 20 % ( G20 ) , 50 % ( G50 ) , or 80 % ( G80 ) one repetition maximum ( 1RM ) for 8 - 12 weeks or to a nontraining control group ( CON ) . Participants trained twice per week ( five exercises ; three sets of eight rapidly concentric and slow eccentric repetitions ) using pneumatic resistance machines . Repeated- measures analysis of variance and covariance ( ANOVA and ANCOVA ) were used to determine the effects of training . RESULTS Average peak power increased significantly and similarly in G80 ( 14 + /- 8 % ) , G50 ( 15 + /- 9 % ) , and G20 ( 14 + /- 6 % ) compared to CON ( 3 + /- 6 % ) ( p < .0001 ) . By contrast , a positive dose-response relationship with training intensity was observed for relative changes in average strength ( r = .40 , p = .0009 ) and endurance ( r = .43 , p = .0005 ) . Average strength increased in G80 ( 20 + /- 7 % ) , G50 ( 16 + /- 7 % ) , and G20 ( 13 + /- 7 % ) compared to CON ( 4 + /- 4 % ) ( p < .0001 ) . Average muscle endurance increased in G80 ( 185 + /- 126 % , p < .0001 ) , G50 ( 103 + /- 75 % , p = .0004 ) , and G20 ( 82 + /- 57 % , p = .0078 ) compared to CON ( 28 + /- 29 % ) . CONCLUSION Peak muscle power may be improved similarly using light , moderate , or heavy resistances , whereas there is a dose-response relationship between training intensity and muscle strength and endurance changes . Therefore , using heavy loads during explosive resistance training may be the most effective strategy to achieve simultaneous improvements in muscle strength , power , and endurance in older adults PURPOSE The purpose of this study was to examine the impact of moderate-intensity , progressive , upper-body resistance training ( RT ) on muscle strength and perceived performance of household physical activities ( HPA ) among women in cardiac rehabilitation . METHODS The 10-week , pretest-posttest , experiment r and omized women to either usual care ( UC ) aerobic exercise or RT . Muscle strength for 5 upper-body RT exercises ( chest press , shoulder press , biceps curl , lateral row , and triceps extension ) was measured using the 1-Repetition Maximum Assessment . The RT group progressively increased weight lifted using 40 % , 50 % , and 60 % of obtained 1-Repetition Maximum Assessment at 3-week intervals . Perceived performance of HPA was measured with the Kimble Household Activities Scale . RESULTS The RT group ( n = 16 , mean age 64 ± 11 ) significantly increased muscle strength in all 5 exercises in comparison with the UC group ( n = 14 , mean age 65 ± 10 ) ( chest press , 18 % vs 11 % ; shoulder press , 24 % vs 14 % ; biceps curl , 21 % vs 12 % ; lateral row , 32 % vs 9 % ; and triceps extension , 28 % vs 20 % , respectively ) . By study end , Household Activities Scale scores significantly increased ( F = 13.878 , P = .001 ) in the RT group ( 8.75 ± 3.19 vs 11.25 ± 2.14 ) , whereas scores in the UC group decreased ( 8.60 ± 3.11 vs 6.86 ± 4.13 ) . CONCLUSION Progressive upper-body RT in women shows promise as an effective tool to increase muscle strength and improve the ability to perform HPA after a cardiac event . Beginning RT early after a cardiac event in a monitored cardiac rehabilitation environment can maximize the strengthening benefit PURPOSE This study examined the effects of performing combined resistance and aerobic training , versus aerobic training alone , in patients with coronary artery disease . METHODS Thirty-six patients with coronary artery disease were r and omized to either an aerobic-only training group ( AE ) or a combined aerobic and resistance training group ( AE + R ) . Both groups performed 30 minutes of aerobic exercise 3 days/week for 6 months . In addition , AE + R group performed two sets of resistance exercise on seven different Nautilus machines after completion of aerobic training each day . Twenty patients ( AE : n = 10 ; AE + R : n = 10 ) completed the training protocol with > 70 % attendance . RESULTS Strength gains for AE + R group were greater than for AE group on six of seven resistance machines ( P < 0.05 ) . VO2peak increased after training for both AE and AE + R ( P < 0.01 ) with no difference in improvement between the groups . Resting and submaximal exercise heart rates and rate-pressure product were lower after training in the AE + R group ( P < 0.01 ) , but not in the AE group . AE + R increased lean mass in arm , trunk , and total body regions ( P < 0.01 ) , while AE increased lean mass in trunk region only ( P < 0.01 ) . Percent body fat was reduced for AE + R after training ( P < 0.05 ) with a between group trend toward reduced body fat ( P = 0.09 ) . Lean mass gain significantly correlated with strength increase in five of seven resistance exercises for AE + R. CONCLUSIONS Resistance training adds to the effects of aerobic training in cardiac rehabilitation patients by improving muscular strength , increasing lean body mass , and reducing body fat Background Resistance training ( RT ) is safe and practicable in low-risk population s with coronary artery disease . In patients with left ventricular ( LV ) dysfunction after an acute ischaemic event , few data exist about the impact of RT on LV remodelling . Methods In this prospect i ve , r and omized , controlled study , 38 patients , after a first myocardial infa rct ion and a maximum ejection fraction ( EF ) of 45 % , were assigned either to combined endurance training (ET)/RT ( n = 17 ; 15 men ; 54.7 ± 9.4 years and EF : 40.3 ± 4.5 % ) or to ET alone ( n = 21 ; 17 men ; 57.0 ± 9.6 years and EF : 41.9 ± 4.9 % ) for 12 weeks . ET was effectuated at an intensity of 70–85 % of peak heart rate ; RT , between 40 and 60 % of the one-repetition maximum . LV remodelling was assessed by MRI . Results No statistically significant differences between the groups in the changes of end-diastolic volume ( P = 0.914 ) , LV mass ( P = 0.885 ) and EF ( P = 0.763 ) were observed . Over 1 year , the end-diastolic volume increased from 206 ± 41 to 210 ± 48 ml ( P = 0.379 ) vs. 183 ± 44 to 186 ± 52 ml ( P = 0.586 ) ; LV mass from 149 ± 28 to 155 ± 31 g ( P = 0.408 ) vs. 144 ± 36 to 149 ± 42 g ( P = 0.227 ) and EF from 49.1 ± 12.3 to 49.3 ± 12.0 % ( P = 0.959 ) vs. 51.5 ± 13.1 to 54.1 % ( P = 0.463 ) , in the ET/RT and ET groups , respectively . Peak VO2 and muscle strength increased significantly in both groups , but no difference between the groups was noticed . Conclusion RT with an intensity of up to 60 % of the one-repetition maximum , after an acute myocardial infa rct ion , does not lead to a more pronounced LV dilatation than ET alone . A combined ET/RT , or ET alone , for 3 months can both increase the peak VO2 and muscle strength significantly Background — In coronary artery disease , exercise training ( ET ) is associated with an improvement in endothelial function , but little is known about the relative effect of different types of training . The purpose of this study was to prospect ively evaluate the effect of different types of ET on endothelial function in 209 patients after a first recent acute myocardial infa rct ion . Methods and Results — Endothelial function was evaluated before and after 4 weeks of different types of ET and after 1 month of detraining by measuring flow-mediated dilation and von Willebr and factor levels at baseline and after ET . Patients were r and omized into 4 groups : group 1 , aerobic ET ( n=52 ) ; group 2 , resistance training ( n=54 ) ; group 3 , resistance plus aerobic training ( n=53 ) ; and group 4 , no training ( n=50 ) . At baseline , flow-mediated dilation was 4.5±2.6 % in group 1 , 4.01±1.6 % in group 2 , 4.4±4 % in group 3 , and 4.3±2.3 % in group 4 ( P = NS ) . After ET , flow-mediated dilation increased to 9.9±2.5 % in group 1 , 10.1±2.6 % in group 2 , and 10.8±3 % in group 3 ( P<0.01 versus baseline for all groups ) ; it also increased in group 4 but to a much lesser extent ( to 5.1±2.5 % ; P<0.01 versus trained groups ) . The von Willebr and factor level after ET decreased by 16 % ( P<0.01 ) similarly in groups 1 , 2 , and 3 but remained unchanged in group 4 . Detraining returned flow-mediated dilation to baseline levels ( P<0.01 versus posttraining ) . Conclusion — In patients with recent acute myocardial infa rct ion , ET was associated with improved endothelial function independently of the type of training , but this effect disappeared after 1 month of detraining BACKGROUND We examined the effects of combined resistance and aerobic training on l and versus combined resistance and aerobic training in water in patients with coronary artery disease . METHODS Thirty-four patients were r and omly assigned to l and exercise ( LE , n = 12 ) , water exercise ( WE , n = 12 ) , and control ( n = 10 ) groups . The LE group trained 4 times per week , twice with aerobic exercise and twice with resistance training . The WE program included aquatic aerobic activities 2 times per week and resistance exercise at the same frequency carried out in water . The duration of the training programs was 4 months . Body composition measurements , blood lipids , exercise stress testing , and muscular strength were obtained at the beginning and at the end of the training period . RESULTS After 4 months of training , analysis of covariance revealed that body weight and sum of skinfolds were lower for WE and LE groups than for the control group . Patients who trained in water improved exercise time ( + 11.7 % vs + 8.1 % ) and maximum strength ( + 12.8 % vs + 12.9 % ) in a similar manner compared to the patients who trained on l and . Total cholesterol ( WE -4.4 % , LE -3.3 % ) and triglycerides ( WE -10.2 % , LE -11.8 % ) decreased significantly for both exercise groups but not for the control group . CONCLUSIONS Exercise programs that combine resistance and aerobic exercise performed either on l and or in water can both improve exercise tolerance and muscular strength in patients with coronary artery disease . Furthermore , both programs induce similar favorable adaptations on total cholesterol , triglycerides , and body composition Summary Background In patients with coronary heart disease , both arterial stiffness and wave reflections are increased and predict unfavorable cardiovascular events . Cardiac rehabilitation has the goal to reduce risk factors and slow the progression of the disease . The aim of this study was to prospect ively determine the impact of an ambulatory cardiac rehabilitation program on pulsatile hemodynamics . Methods Male patients after coronary interventions , bypass surgery , or acute coronary syndromes underwent exercise and resistance training . Before and after the program , pulsatile hemodynamics was measured . Exercise capacity was assessed with an incremental cycle ergometer protocol . A detailed two-dimensional and Doppler echocardiogram was obtained for systolic and diastolic left ventricular function . Results A total of 27 men participated in the study . After the intervention ( n = 24 ) , carotid – femoral pulse wave velocity decreased significantly from 8.7 ( st and ard deviation ( SD ) : 1.7 ) to 7.9 ( SD : 1.9 ) m/s ( p = 0.019 ) , and augmentation index normalized for a heart rate of 75/min decreased significantly from 20.4 ( SD : 8.7 ) to 17.5 ( SD : 8.1 ; p = 0.017 ) . Conclusion The results suggest that a structured ambulatory rehabilitation program may improve pulsatile hemodynamics in coronary artery disease ( CAD ) patients .ZusammenfassungGrundlagenPatienten mit koronarer Herzkrankheit ( KHK ) weisen eine erhöhte arterielle Gefäßsteifigkeit und Pulswellenreflexionen auf , die ein Prädikator für kardiovaskuläre Ereignisse sind . Die kardiologische Rehabilitation hat das Ziel , Risikofaktoren zu reduzieren und das Fortschreiten der Krankheit zu verlangsamen . Das Ziel der Studie war es , prospektiv die Auswirkung eines ambulanten kardiologischen Rehabilitationsprogrammes auf die pulsatile Hämodynamik festzustellen . Method eMännliche Patienten nach Koronarinterventionen , koronarer Bypass-Operation oder nach akutem Koronarsyndrom absolvierten ein Ausdauer- und Krafttraining . Vor und nach dem Programm wurde die pulsatile Hämodynamik ermittelt . Mittels Fahrradergometrie wurde die Leistungsfähigkeit und durch eine 2-D und Doppler Echokardiographie die systolische und diastolische Herzfunktion festgestellt . Ergebnisse27 Männer nahmen an der Studie teil . Nach der Intervention ( n = 24 ) , verringerten sich die Cf-Pulswellengeschwindigkeit signifikant von 8,7 ( SD 1,7 ) auf 7,9 ( SD 1,9 ) m/s ( p = 0,019 ) und der Augmentations-Index@75 von 20,4 ( SD 8,7 ) auf 17,5 ( SD 8,1 ) ( p = 0,017).SchlussfolgerungDie Ergebnisse deuten darauf hin , dass eine strukturierte ambulante Rehabilitation die pulsatile Hämodynamik bei KHK Patienten verbessern könnte Objective To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength , functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program . Methods A prospect i ve , quasi-experimental study with 24 patients who underwent coronary artery bypass and were r and omly assigned to two groups in the Phase II cardiac rehabilitation program : inspiratory muscle training program associated with combined training ( aerobic and resistance ) group ( GCR + IMT , n=12 ) and combined training with respiratory exercises group ( GCR , n=12 ) , over a period of 12 weeks , with two sessions per week . Before and after intervention , the following measurements were obtained : maximal inspiratory and expiratory pressures ( PImax and PEmax ) , peak oxygen consumption ( peak VO2 ) and quality of life scores . Data were compared between pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student 's t-test , except the categorical variables , which were compared using the Chi-square test . Values of P<0.05 were considered statistically significant . Results Compared to GCR , the GCR + IMT group showed larger increments in PImax ( P<0.001 ) , PEmax ( P<0.001 ) , peak VO2 ( P<0.001 ) and quality of life scores ( P<0.001 ) . Conclusion The present study demonstrated that the addition of inspiratory muscle training , even when applied for a short period , may potentiate the effects of combined aerobic and resistance training , becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation Physical activity energy expenditure ( PAEE ) is a determinant of prognosis and fitness in older patients with coronary heart disease ( CHD ) . PAEE and total energy expenditure ( TEE ) are closely related to fatness , physical function , and metabolic risk in older individuals . The goal of this study was to assess effects of resistance training on PAEE , TEE , and fitness in older women with chronic CHD and physical activity limitations ( N = 51 , mean age : 72 + 5 yr ) . The study intervention consisted of a progressive , 6-mo program of resistance training vs. a control group condition of low-intensity yoga and deep breathing . The study interventions were completed by 42 of the 51 participants . The intervention group manifested a 177 + /- 213 kcal/day ( + 9 % ) increase in TEE , pre- to posttraining , measured by the doubly labeled water technique during a nonexercise 10-day period ( P < 0.03 vs. controls ) . This was due to a 50 + /- 74 kcal/day ( 4 % ) increase in resting metabolic rate measured by indirect calorimetry ( P < 0.01 , P < 0.05 vs. controls ) and a 123 + /- 214 kcal/day ( 9 % ) increase in PAEE ( P < 0.03 , P = 0.12 vs. controls ) . Resistance training was associated with significant increases in upper and lower body strength , but no change in fat-free mass , measured by dual X-ray absorptiometry , or left ventricular function , measured by echocardiography and Doppler . Women in the control group showed no alterations in TEE or its determinants . There were no changes between groups in body composition , aerobic capacity , or measures of mental depression . These results demonstrate that resistance training of 6-mo duration leads to an increase in TEE and PAEE in older women with chronic CHD OBJECTIVE Study the effect of muscle strength training on muscle strength , maximal oxygen uptake ( VO2max ) , hemodynamic and anthropometric parameters as well as quality of life after coronary artery bypass grafting ( CABG ) . METHODS After CABG surgery , 32 patients were r and omized into two groups . The first group was to perform aerobic-type training with a cycle ergometer ( AT=16 ) . The second group was to perform low-intensity muscle strength training of the quadriceps and hamstrings using an isokinetic dynamometer ( i.e. 20 to 30 % of peak torque ) ( ST=16 ) . Before and after the strength training program we conducted a stress test , evaluation of isokinetic force production , 6-minute walking test , body impedance analysis ( BIA ) and SF-36 quality of life test . RESULTS Compared to the AT group , the ST group showed better results with improved quadriceps strength ( 48.2 % vs. 8.2 % ) , VO2max ( P<.001 ) and diastolic blood pressure at rest ( P=0.01 ) . Quality of life improved in both groups . CONCLUSION The dynamic-resistance muscle strength training protocol using isokinetic dynamometer can safely ( i.e. without clinical symptoms or changes to the ECG and arterial blood pressure ) improve muscle strength and VO2max without any major risks in patients post-CABG . These findings should encourage additional studies to vali date the relevance of these strength training modalities in rehabilitation centers Background The purpose of the present study was to assess the training and detraining effects on physiological parameters result ing from a combined strength and aerobic exercise programme in patients with coronary artery disease . Design and methods Thirty male coronary artery disease patients were r and omly assigned to an exercise ( n = 16 ) and control group ( n = 14 ) . Patients in the exercise group participated in a supervised exercise programme for 8 months and were followed for 3 months after training cessation . The programme consisted of two sessions of circuit weight training and two sessions of aerobic training . Cardiopulmonary testing and muscular strength were assessed at baseline and after 4 and 8 months of training as well as after 3 months of detraining . Results The exercise training programme result ed in significant improvement in cardiorespiratory fitness ( V O2peak 15.4 % and exercise time 14 % ) after 8 months . Muscular strength also increased significantly in all exercises by an average of 28 % ( upper body 25.5 % and lower body 35.4 % ) . Three months of detraining , however , result ed in a 10 % regression in V O2peak , 6.7 % in exercise time , 12 % in upper body strength and 15.7 % in lower body strength . Conclusions The above results indicate that a significant part of the favourable adaptations obtained after prolonged training is practically lost within 3 months of detraining . Therefore , patients with coronary artery disease should follow a systematic exercise programme throughout life in order to improve cardiovascular function , muscular strength and ameliorate their health status . Eur J Cardiovasc Prev Rehabil 13:375–380 © 2006 The European Society of Background : The aim of this study was to evaluate the effects of high frequency exercise for patients before and after an elective percutaneous coronary intervention ( PCI ) , with special reference to maximal aerobic capacity , muscle function , health related quality of life ( HRQoL ) , waist – hip ratio ( WHR ) and restenosis . Methods : A r and omised , controlled study was performed in Sweden between 2004 and 2006 in thirty-seven patients ( five women ) with stable coronary artery disease ( CAD ) , age 63.6 ± 6.9 years , r and omised to either high frequency exercise or control group . The patients in the training group performed three endurance resistance exercises and trained on a cycle ergometer 30 min , 5 times a week for 8 months at 70 % of VO2max . Results : Patients in the training group significantly improved their maximal aerobic capacity ( 15 ( 9–46 ) vs. 8 (0–18)% p ≤ 0.05 ) , shoulder flexion ( p ≤ 0.01 ) , shoulder abduction ( p ≤ 0.01 ) and heel-lift ( p ≤ 0.05 ) compared to the control group . There were no significant differences between the groups in HRQoL , WHR and restenosis . Conclusion : High frequency exercise in patients treated with PCI seems to improve maximal aerobic capacity and muscle function , which may reduce the risks of further progression of atherosclerosis . However , further larger studies are needed to fully investigate the effects of exercise in patients with PCI BACKGROUND Older women with coronary artery disease ( CAD ) have reduced peak aerobic power ( Vo(2)peak ) , muscle strength , and quality of life ( QOL ) . Exercise interventions that can improve Vo(2)peak and muscle strength may also result in an improvement in QOL . This study compared the effect of aerobic training ( AT ) or combined aerobic and strength training ( COMT ) on Vo(2)peak , distance walked in 6 min , upper- and lower-extremity maximal strength , and QOL in 18 women ( age range , 60 to 80 years ) with documented CAD . METHODS After baseline testing , subjects were r and omly assigned to AT ( treadmill and cycle exercise , n = 9 ) or COMT ( treadmill and cycle exercise plus upper- and lower-extremity strength training , n = 9 ) , and each group exercised 3 d/wk for 8 weeks . RESULTS Both AT and COMT result ed in a similar increase in Vo(2)peak , distance walked in 6 min , lower-extremity strength , and emotional and global QOL . COMT improved upper-extremity strength , and physical and social QOL , which was unchanged after AT . CONCLUSIONS Older women with CAD should perform aerobic and strength training to attain optimal improvements in overall physical fitness and QOL This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence BACKGROUND Cardiovascular benefits of resistance training in cardiac patients have been suggested but not studied in a r and omized , controlled trial of circuit weight training ( CWT ) without an aerobic exercise component . The purpose of the current study was to examine the effects of 10 weeks of CWT on muscular strength , peak oxygen consumption ( peak VO2 ) , and myocardial oxygen dem and ( mVO2 ) in men after coronary artery bypass surgery . METHODS Twenty-six , post-coronary bypass male subjects ( mean 19 months after bypass ) , aged 60 + /- 8.5 years , were r and omly allocated to 10 weeks of CWT at 40 to 60 % of maximum voluntary contraction ( n = 12 ) or to a control group ( n = 14 ) . Muscular strength was assessed using a modified one repetition maximum technique . Peak VO2 was recorded during symptom-limited treadmill exercise . Rate pressure product , as an indirect measure of mVO2 , was measured during isometric , isodynamic , and dynamic exercise . RESULTS No ischemic symptoms nor electrocardiographic changes were recorded during testing or training . Strength increased by 18 % ( P < 0.005 ) in five out of seven exercises in the training group , but was unchanged in the control group . Training did not improve peak VO2 . Rate pressure product during isometric and isodynamic exercise decreased from pre- to post-testing ( P < 0.05 ) but was equivalent to that seen in the control group . CONCLUSIONS Moderate intensity CWT is safe and can improve strength in selected low-risk patients after coronary artery bypass surgery . However , it does not significantly increase peak VO2 nor reduce mVO2 during isometric , isodynamic , and dynamic exercise Background : Cardiac rehabilitation ( CR ) programmes have increased their availability and exp and ed their eligibility criteria . This study sought to identify current predictors and reasons influencing myocardial infa rct ion patients ’ pre-discharge intentions to attend CR . Methods : Patients in this longitudinal , prospect i ve , five site study completed question naires that surveyed their intentions to attend , attendance and main reasons for non-attendance at CR . Results : 84 % of the 1172 patients indicated that they intended to attend CR . Multivariate analyses revealed that age , employment and earlier history of myocardial infa rct ion were significant predictors of intention to attend CR , yet contributed to only a small proportion of the variance . The main reasons given for not intending to attend CR were lack of interest and perception that the programme would not be beneficial . Other obstacles included work , transport or time . A total of 708 ( 60 % ) patients responded at 12 months , and of these , 44 % who did not intend to attend CR had attended . Conclusion : Patient sociodemographic and clinical profile , although significant , are not major predictors of intention to attend CR . Lack of interest and misconceptions regarding CR are cited as key barriers . Some of these seem to have been addressed post discharge as a good proportion of patients who had not intended to attend CR did change their minds and attended . Motivation of patients to participate in CR , including the identification of barriers and the provision of comprehensive information about the purpose and varied formats of CR programmes , could be used to help further address barriers to attendance Coronary artery disease affects patients in their most productive years and may lead to considerable time lost from work [ 1 - 3 ] . Many persons with coronary artery disease may leave the workforce entirely , either of their own volition or as a result of employer policies . Because coronary revascularization reduces myocardial ischemia and anginal symptoms and decreases the risk for death in higher-risk groups [ 4 ] , it may also improve employment after revascularization among patients with coronary artery disease . R and omized trials comparing coronary bypass surgery with medical therapy have shown little difference in subsequent employment [ 5 , 6 ] . However , convalescence after bypass surgery may be lengthy ; this may limit return to work even among successfully treated patients . Coronary angioplasty offers the possibility of substantial relief of angina with a short convalescence , thereby speeding return to normal activities , including employment [ 7 ] . We analyzed patterns of employment among patients in the Bypass Angioplasty Revascularization Investigation ( BARI ) , a r and omized clinical trial of coronary angioplasty or coronary bypass surgery [ 8 - 10 ] . Methods The Study of Economics and Quality of Life ( SEQOL ) was conducted in 7 of the 18 BARI clinical centers [ 11 , 12 ] . Eligible patients had myocardial ischemia severe enough to warrant coronary revascularization and multivessel coronary disease suitable for balloon angioplasty or for bypass surgery . At study entry , patients enrolled in SEQOL gave detailed information on their employment , including hours worked per week , job type , physical dem and s , and mental stress [ 11 ] . Employment status , including type of work performed , hours worked per week , and time missed from work , was up date d every 3 months during follow-up . Patients who stopped work during follow-up gave information on the date that work ended and the main reason for stopping work . The main outcome measure was total time worked during follow-up , defined as the percentage of full-time equivalent employment of 40 hours a week for 13 weeks per quarter . The time worked in each quarter throughout follow-up was summed over 4 years to provide a summary measure of employment ranging from 0 to 4 full-time equivalent years . Time worked by patients who died during follow-up was included in this analysis . Between-group comparisons were done by using the Wilcoxon rank-sum test and multivariable analysis was done with backward , stepwise linear regression . Confidence intervals were calculated by using the percentile bootstrap method . Analyses were performed by using SAS version 6.12 ( SAS , Inc. , Cary , North Carolina ) and S-PLUS version 3.4 , release 1 ( MathSoft , Inc. , Seattle , Washington ) . Results A total of 934 patients were enrolled in SEQOL ; of these , 409 were employed at study entry . One hundred ninety-two employed patients were r and omly assigned to undergo coronary angioplasty and 217 were assigned to undergo coronary bypass surgery . The baseline clinical and job-related characteristics of the employed angioplasty and surgery patients were well balanced ( data not shown ) . Over 4 years of follow-up , 157 ( 82 % ) patients in the angioplasty group and 177 ( 82 % ) patients in the surgery group resumed work . Angioplasty patients who resumed work did so at a median of 4.9 weeks ( interquartile range , 2.7 to 10.9 weeks ) after r and omization compared with 10.9 weeks ( interquartile range , 7.7 to 14.4 weeks ) for surgery patients ( difference , 6 weeks [ 95 % CI , 3.4 to 7.0 weeks ] ) . After 4 years of follow-up , angioplasty patients had worked an average of 2.23 years compared with 2.13 years for surgery patients ( difference , 0.11 years [ CI , 0.24 to 0.45 years ] ) . The average time spent working decreased progressively throughout followup in both groups , principally as a result of stopping work entirely rather than reducing the number of hours worked per week . Similar numbers of angioplasty and surgery patients stopped work because of heart disease ( 49 and 47 patients , respectively ) , other health conditions ( 14 and 11 patients ) , retirement not induced by health problems ( 23 and 37 patients ) , or other reasons ( 28 and 32 patients ) . Because the long-term employment of patients who underwent angioplasty did not differ significantly from that of patients who underwent surgery , these two groups were combined to analyze other factors associated with employment . Results of univariable analyses are shown in Table 1 , and results of multivariable analysis are shown in Table 2 . The strongest factor affecting long-term employment was patient age at study entry . The relation between age and time worked was U-shaped , with patients 60 to 64 years of age at study entry working less during follow-up than both younger and older patients ( Table 2 ) . Patients who initially worked full-time worked more during follow-up , as did patients who planned to return to the same job . Patients who had a single , private source of medical insurance at baseline were more likely to continue working ( Table 2 ) . Table 1 . Employment during 4 Years of Follow-up according to Baseline Characteristics Table 2 . Multivariable Model of 4-Year , Full-Time Equivalent Employment * Medical factors were less predictive of long-term employment patterns than were demographic factors and job characteristics . Of the medical characteristics that were significant in the univariable analysis ( Table 1 ) , only left ventricular function was significant in the multivariable analysis ( Table 2 ) . Discussion Among patients in a r and omized trial , those treated with angioplasty returned to work significantly faster than patients treated with bypass surgery , but this did not translate into greater long-term employment . Long-term employment patterns were associated more with patient age and job characteristics than with measures of illness severity or the method of coronary revascularization . Successful coronary angioplasty avoids the need for general anesthesia , cardiopulmonary bypass , and a large chest incision , allowing patients to return to normal activity sooner than patients undergoing coronary bypass surgery . Timing of return to work after medical illness and surgical procedures is governed by the intrinsic rate of physical recovery , physician advice , employer policies , and social convention . We did not assess the latter three factors in this study and could not evaluate their relative importance to resumption of employment . Our results suggest that the speed with which a patient can resume normal activities , including employment , is sensitive to the results of medical interventions . Therapies , such as angioplasty , that allow a more rapid convalescence have medical , social , and economic benefits . Surgery patients in BARI have been shown to have fewer anginal symptoms , better objective measures of exercise tolerance , and reduced need for repeated revascularization procedures [ 9 , 10 ] , but these results did not improve long-term employment . Other r and omized trials of angioplasty compared with bypass surgery [ 13 - 15 ] or with medical therapy [ 15 - 17 ] have also shown little effect of clinical ly successful coronary revascularization on employment . These results are consistent with observations in less selected population s [ 2 , 3 , 18 ] and indicate that nonmedical factors are the most important determinants of long-term employment . The seriousness of coronary revascularization may prompt many patients to reconsider their goals in life , leading them to reduce work and redirect themselves toward their families or other priorities , even after a successful clinical result . Older age was strongly correlated with a lower rate of long-term employment , with one intriguing exception . Patients 65 years of age or older who were working at study entry worked significantly more than patients 60 to 64 years of age ( Table 2 ) . One potential explanation is that patients 65 years of age and older who were still working had already passed up one opportunity to retire and thus would be more likely to continue working even after coronary revascularization , whereas patients aged 60 to 64 at study entry had not yet faced a retirement decision . This interpretation tends to be corroborated by the work experience of the entire cohort of 934 patients , which included those who had retired before r and omization and those who were still working at study entry . The amount of time worked in the entire cohort decreased progressively with age , from 2.19 years for patients younger than 55 years of age to 1.54 years for patients 55 to 59 years , 0.81 years for patients 60 to 64 years of age , and 0.24 years for patients 65 years of age or older . Patients who worked past the traditional age of retirement seem to be self-selected for continued employment , even in the face of major surgery . Another interesting observation was that patients who had a single source of private health insurance , probably obtained through their job , tended to work an average of 0.53 years more during follow-up ( Table 2 ) . Patients with preexisting conditions , such as heart disease , may be reluctant to leave their jobs unless they can obtain health insurance through another source . Unfortunately , before patients are eligible for Medicare at 65 years of age , few sources of private health insurance are available for those who lose their employment-based coverage . Our findings suggest that ability to maintain health insurance coverage may be an important consideration for patients with heart disease who are deciding whether to retire . Several caveats should be considered in the interpretation of our findings . First , patients were selected for BARI on the basis of stringent inclusion and exclusion criteria ; therefore , they may not be representative of all employed patients with coronary artery disease . Our findings comparing coronary angioplasty and coronary bypass surgery , however , are based on a r and omized comparison and therefore have high validity . In addition , these results are consistent BACKGROUND Developing adequate levels of muscular strength in the cardiac rehabilitation ( CR ) patient helps return the patient to an active lifestyle . This study evaluated the effects and safety of an 8-week high-intensity strength training ( ST ) program combined with a traditional aerobic-based CR program on the muscular strength of a diverse phase II CR population . METHODS Sixty-one phase II CR patients ( age = 60.5 + /- 10.6 years ) stratified by risk ( high risk : n = 18 , ejection fraction = 23.6 + /- 7.8 % ; intermediate risk : n = 19 , ejection fraction = 40.0 + /- 4.6 % ; low risk : n = 24 , ejection fraction = 58.0 + /- 7.7 % ) and gender ( males = 46 , females = 15 ) participated . One repetition maximum ( 1RM ) testing was performed on the horizontal squat , shoulder press , leg extension , lat pulldown , and biceps curl . Patients performed two sets of each exercise 2 days per week at an intensity that started at 60 % 1RM and progressed to 80 % 1RM by week 4 . Weeks 4 to 8 intensity was adjusted individually to maintain 8RM per set . Blood pressure and heart rate/rhythm responses to 1RM testing were monitored in high-risk patients . Muscle soreness and injury were monitored for all patients immediately after 1RM testing and on days 2 and 7 . RESULTS All patient groups made significant gains ( P < 0.05 ) in muscle strength ( mean increase : lower body = 15.3 % , upper body = 16.7 % ) . No injury or significant muscle soreness occurred due to 1RM testing . No abnormal heart rate/rhythm or blood pressure responses occurred in high-risk patients . CONCLUSIONS Diverse phase II CR patients can improve their strength significantly with a combination of high-intensity strength and aerobic training The effect of hydraulic circuit training ( HCT ) on stroke volume ( SV ) , cardiac output ( Qc ) , aerobic power ( peak VO2 ) , and muscular strength and endurance was evaluated in 24 post-coronary artery bypass ( CABS ) patients ( mean age = 52.8 + /- 2.6 yr ) . All assessment s other than muscular strength and endurance were based upon a symptom limited grade d exercise test on a bicycle ergometer . Muscular strength and endurance were assessed on a Cybex II isokinetic dynamometer . Sixteen patients were assigned r and omly to 8 wk of cycle training or HCT ( N = 8 in each ) . Subjects assigned to cycle training exercised on bicycle ergometers . The HCT group exercised on a three-station circuit , completing three circuits per day . Each circuit consisted of three 20 s work intervals at each station with a 1:1 work : rest ratio . Results from the training groups were compared with results from eight patients who served as a nonexercising control group . Following training the peak VO2 was significantly increased in the training groups ( 20 % and 11 % for the cycle and HCT groups , respectively ; P less than 0.05 ) . For both training groups , the increase in peak VO2 was associated with increases in SV and Qc and a reduction in heart rate ( HR ) at submaximal levels of exercise ( P less than 0.05 ) . Only the HCT group demonstrated an increase in both muscular strength and endurance during knee and shoulder exercises ( P less than 0.05 ) . These findings suggest that a program of HCT can elicit improvements in cardiovascular fitness and muscular strength and endurance in post-CABS patients OBJECTIVES To determine the effects of resistance training combined with either moderate-intensity endurance or low-volume high-intensity interval training on cardiovascular risk profiles in patients with coronary artery disease . DESIGN Factorial repeated- measures study design . METHODS Nineteen patients were r and omized into moderate-intensity endurance ( n = 10 ) or high-intensity interval ( n = 9 ) groups , and attended 2 supervised exercise sessions a week for 6-months . The first 3-months involved exclusive moderate-intensity endurance or high-intensity interval exercise , after which progressive resistance training was added to both groups for the remaining 3-months . Fitness ( VO(2)peak ) , blood pressure and heart rate , lipid profiles and health related quality of life assessment s were performed at pretraining , 3 and 6-months training . RESULTS VO(2)peak increased from pretraining to 3-months in both groups ( moderate-intensity endurance : 19.8 ± 7.3 vs. 23.2 ± 7.4 ml kg(-1)min(-1 ) ; high-intensity interval : 21.1 ± 3.3 vs. 26.4 ± 5.2 ml kg(-1)min(-1 ) , p<0.001 ) with no further increase at 6-months . Self-evaluated health and high-density lipoprotein were increased following 6-months of moderate-intensity endurance exercise , while all remaining indices were unchanged . Low-volume high-intensity interval exercise did not elicit improvements in lipids or health related quality of life . Blood pressures and heart rates were unchanged with training in both groups . CONCLUSIONS Findings from our pilot study suggest improvements in fitness occur within the first few months of training in patients with coronary artery disease , after which the addition of resistance training to moderate-intensity endurance and high-intensity interval exercise elicited no further improvements . Given the importance of resistance training in cardiac rehabilitation , additional research is required to determine its effectiveness when combined with high-intensity interval exercise OBJECTIVE To compare the effect and sustainability of 6 months combined aerobic/strength training vs aerobic training alone on quality of life in women after coronary artery by-pass graft surgery or myocardial infa rct ion . DESIGN Prospect i ve , 2-group , r and omized controlled trial . PARTICIPANTS Ninety-two women who were 8 - 10 weeks post-coronary artery by-pass graft surgery or myocardial infa rct ion , able to attend supervised exercise , and fluent in English . METHODS The aerobic training alone group had supervised exercise twice a week for 6 months . The aerobic/strength training group received aerobic training plus upper and lower body resistance exercises . The amount of active exercise time was matched between groups . The primary outcome , quality of life , was measured by the MOS SF-36 ; secondary outcomes were self-efficacy , strength and exercise capacity . RESULTS After 6 months of supervised exercise training both groups showed statistically significant improvements in physical quality of life ( p = 0.0002 ) , peak VO2 ( 19 % in aerobic/strength training vs 22 % in aerobic training alone ) , strength ( p < 0.0001 ) and self-efficacy for stair climbing ( p = 0.0024 ) , lifting ( p < 0.0001 ) and walking ( p = 0.0012 ) . However , by 1-year follow-up there was a statistically significant difference in physical quality of life in favor of the aerobic/strength training group ( p = 0.05 ) . CONCLUSION Women with coronary artery disease st and to benefit from both aerobic training alone and aerobic/strength training . However , continued improvement in physical quality of life may be achieved through combined strength and aerobic training PURPOSE The purpose of this study was to compare resistance training ( RT ) ( one set vs three sets ) combined with aerobic training ( AT ) versus AT alone in persons with coronary artery disease . METHODS Subjects ( n = 72 ) were r and omized to AT ( 5 d x wk(-1 ) ) or combined AT ( 3 d x wk(-1 ) ) with either one set ( AT/RT1 ) or three sets ( AT/RT3 ) of RT performed 2 d x wk(-1 ) . VO2peak , ventilatory anaerobic threshold ( VAT ) , strength and endurance , body composition , and adherence were measured before and after 29 wk of training . RESULTS Fifty-three subjects ( mean + /- SEM age 61 + /- 2 ) completed the training . The increase from baseline in VO2peak ( L x min(-1 ) ) averaged 11 % for AT ( P < 0.05 ) , 14 % for AT/RT1 ( P < 0.01 ) , and 18 % for AT/RT3 ( P < 0.001 ) , however , the difference between groups was not significant . VAT improved significantly in the AT/RT3 group only ( P < 0.05 ) . The AT/RT3 group gained more lean mass than the AT group ( 1.5 versus 0.4 kg , P < 0.01 ) , yet gains between AT/RT1 and AT were similar ( P = 0.2 ) . Only AT + RT groups demonstrated a reduction in body fat ( P < 0.05 ) . Strength and endurance increased more in the AT + RT groups than AT alone ( P < 0.05 ) . Adherence to number of sets performed was lower in AT/RT3 than AT/RT1 ( P < 0.02 ) . CONCLUSIONS Combined AT + RT yields more pronounced physiological adaptations than AT alone and appears to be superior in producing improvements in VO2peak , muscular strength and endurance , and body composition . The data support the use of multiple set RT for patients desiring an increased RT stimulus which may further augment parameters that affect VO2peak , VAT , lower body endurance , and muscle mass in a cardiac population OBJECTIVES To assess changes in participation in society ( frequency , restrictions , satisfaction ) during and after cardiac rehabilitation ( CR ) and to assess associations between participation and heath-related quality of life ( HRQOL ) . DESIGN Prospect i ve cohort study . SETTING Outpatient CR center . PARTICIPANTS Patients with coronary artery disease ( N=121 ; mean age , 57y ; 96 men [ 79 % ] ) . INTERVENTIONS Multidisciplinary CR . MAIN OUTCOME MEASURES Participation in society was assessed with the Utrecht Scale for Evaluation of Rehabilitation-Participation and HRQOL with the MacNew Heart Disease health-related quality of life question naire . All measurements were performed pre-CR , post-CR , and 1 year after the start of CR . RESULTS Frequency of participation did not change during and after CR . The proportion of patients experiencing restrictions in participation decreased from 69 % pre-CR to 40 % post-CR ( P<.001 ) and 29 % at 1 year ( P<.001 vs post-CR ) . Pre-CR , 71 % of patients were dissatisfied with their participation . This improved to 49 % post-CR ( P<.001 ) and 53 % at 1 year ( P<.001 vs pre-CR ) . Experienced restrictions explained 5 % to 7 % of the improvement in HRQOL during CR and satisfaction with participation explained 10 % to 19 % . CONCLUSIONS Participation in society improves in patients undergoing CR . Despite these improvements , the presence of coronary artery disease is associated with persistent restrictions and dissatisfaction with participation . Because experienced restrictions and dissatisfaction are related to changes in HRQOL it is important to address these aspects of participation during CR This was a prospect i ve , r and omized evaluation of the safety and efficacy of 10 weeks of circuit weight training in patients , aged 35 to 70 years , with documented coronary artery disease . Circuit weight training refers to the performance of a series of weight-lifting exercises using a moderate load with frequent repetitions . Patients had participated in a supervised cardiac rehabilitation program for a minimum of 3 months before the study . Control patients ( n = 20 ) continued with their regular exercise consisting of a walk/jog and volleyball program , while the experimental group ( n = 20 ) substituted circuit weight training for volleyball . No sustained arrhythmias or cardiovascular problems occurred . The experimental group significantly increased treadmill time from 619 to 694 seconds while the treadmill time of the control group did not change . Strength in the experimental group increased by an average of 24 % while there was no change in the control patients . Circuit weight training appears to be safe , and to result in significant increases in aerobic endurance and musculoskeletal strength compared with traditional exercise used in cardiac rehabilitation programs Cardiopulmonary and skeletal muscle effects of combined aerobic and resistance training vs. aerobic training were studied in men with coronary heart disease . Sixteen men with coronary heart disease underwent a cardiopulmonary exercise testing and a quadriceps skeletal muscle fatigue assessment . Patients were divided into two groups and trained in a combined aerobic and resistance or aerobic training group during 7 weeks . Maximal voluntary contraction and isometric endurance time were measured with electromyographic signals recorded from vastus lateralis ( VL ) , rectus femoris ( RF ) and vastus medialis ( VM ) during isometric endurance time . Exercise tolerance increased only in the combined group ( p<0.05 ) . Maximal voluntary contraction and isometric endurance time did not change after training in either group but was performed at 5.8 % higher force output for the combined group . After training , median frequency values were higher for the VL and VM ( p<0.001 ) in the aerobic group and also higher for the VL , RF ( p<0.001 ) and VM ( p<0.05 ) in the combined group . Combined aerobic and resistance training was more effective to improve exercise tolerance , decrease skeletal muscle fatigue and correct neuromuscular alterations in men with coronary heart disease Objective : To examine the effect of eccentric endurance training on exercise capacities in patients with coronary artery disease . Design : R and omized parallel group controlled study . Setting : Cardiac rehabilitation unit , Dijon University Hospital . Participants : Fourteen patients with stable coronary artery disease after percutaneous coronary intervention . Intervention : Patients followed 15 sessions of training ( 1 session per day , 3 days a week ) , either in the concentric group , following a st and ard programme , or in the eccentric group , performing eccentric resistance exercises using both lower limbs on a specifically design ed ergometer . Main outcomes measured : Symptom-limited Vo2 , peak workload , isometric strength of leg extensor and ankle plantar flexors , distance covered during the 6-minute walk test and time to perform the 200-m fast walk test in both groups , before and after the training period . Results : Patients did not report any adverse effects and were highly compliant . All measured parameters improved in eccentric and concentric group , except for 200-m fast walk test : symptom-limited Vo2 ( + 14.2 % versus + 4.6 % ) , peak workload ( + 30.8 % versus + 19.3 % ) , 6-minute walk test distance walked ( + 12.6 % versus + 10.1 % ) and leg extensor strength ( + 7 % versus + 13 % ) improved to a similar degree in both groups ( P<0.01 ) ; ankle plantar flexor strength improved in both groups with a significantly greater increase in the eccentric group ( + 17 % versus + 7 % , P<0.05 ) . Conclusion : Patients with stable coronary artery disease can safely engage in eccentric endurance training , which appears to be as efficient as usual concentric training , with reduced oxygen consumption Information on exercise capacity and training in patients who underwent valvular surgery is scarce . The aim of this study is to evaluate postoperative exercise capacity and functional improvement after exercise training according to the preoperative risk and type of surgery . In this prospect i ve study , 145 patients who underwent aortic valve surgery ( AVS ) or mitral valve surgery ( MVS ) and who were referred for cardiac rehabilitation were stratified according to the preoperative risk ( European System for Cardiac Operative Risk Evaluation [ EuroSCORE ] ) and type of surgery ( sternotomy vs ministernotomy or port access ) . Exercise capacity was evaluated at the start and end of cardiac rehabilitation . Postoperative exercise capacity and the benefit from exercise training were compared between the groups . Patients with a higher preoperative risk had a worse postoperative exercise capacity , with a lower load , peak VO2 , anaerobic threshold and 6-minute walking distance ( all p<0.001 ) , and a higher VE/VCO2 slope ( p=0.01 ) . In MVS , port access patients performed significantly better at baseline ( all p<0.05 ) , but in AVS , ministernotomy patients performed better than sternotomy patients with a concomitant coronary artery bypass graft ( p<0.05 ) . Training result ed in an improvement in exercise capacity in each risk group and each type of surgery ( all p<0.05 ) . This gain in exercise capacity was comparable for the EuroSCORE risk groups and for the types of surgery , for patients after AVS or MVS . In conclusion , exercise capacity after cardiac surgery is related to the preoperative risk and the type of surgery . Despite these differences in postoperative exercise capacity , a similar benefit from exercise training is obtained , regardless of their preoperative risk or type of surgery BACKGROUND Resistance exercise ( RE ) is an important part of cardiac rehabilitation . However , it is not known about the low intensity of RE training that could modify the heart rate variability ( HRV ) , muscular strength and endurance in patients with coronary artery disease ( CAD ) . AIM To investigate the effects of high repetition/low load resistance training ( HR/LL-RT ) program on HRV and muscular strength and endurance in CAD patients . DESIGN R and omized and controlled trial . SETTING Patients seen at the Cardiopulmonary Physical Therapy Laboratory between May 2011 and November 2013 . POPULATION Twenty male patients with CAD were r and omized to a training group ( 61.3±5.2 years ) or control group ( 61±4.4 years ) . METHODS 1 repetition maximum ( 1-RM ) maneuver , discontinuous exercise test on the leg press ( DET-L ) , and resting HRV were performed before and after 8 weeks of HR/LL-RT on a 45 ° leg press . RMSSD , SD1 , mean HR and ApEn indices were calculated . The HR/LL-RT program consisted of a lower limb exercise using a 45 ° leg press ; 3 sets of 20 repetitions , two times a week . The initial load was set at 30 % of the 1-RM load and the duration of the HR/LL-RT program was performed for 8 weeks . RESULTS After 8 weeks of HR/LL-RT there were significant increases of RMSSD and SD1 indices in the training group only ( P<0.05 ) . There was a significant decrease in mean HR after HR/LL-RT in the training group ( P<0.05 ) . There was a significantly higher ApEn after in the training group ( P<0.05 ) . There were significantly higher values in the training group in contrast to the control group ( P<0.05 ) . CONCLUSION These results show positive improvements on HRV , as well as muscle strength and endurance in CAD patients . CLINICAL REHABILITATION IMPACT Eight weeks of HR/LL-RT is an effective sufficient to beneficially modify important outcomes as HRV , muscle strength and endurance in CAD patients PURPOSE This r and omized controlled study assessed whether adding a program of high-intensity strength training ( 80 % of maximum ) to an outpatient cardiac rehabilitation program would be a safe and effective means of improving muscle strength and body composition . METHODS Thirty-eight cardiac patient volunteers ( 29 men and 9 women ) were r and omized to either high-intensity strength training or flexibility training added concurrently to a 12-week outpatient cardiac rehabilitation aerobic exercise program . Muscle strength , local muscle endurance , joint flexibility , maximum treadmill tolerance time , and body composition were measured before and after completion of the training . RESULTS The strength-trained patients ( n = 18 ) had greater increases in mean strength ( 90 + /- 19 % versus 9 + /- 4 % , P < 0.0001 ) and local muscle endurance ( 20 versus 6 times , P < 0.0001 ) , and decreases in mean perceived exertion for lifting the initial one repetition maximum load ( 11 + /- 1 versus 15 + /- 1 , P < 0.0001 ) when compared with flexibility-trained patients ( n = 16 ) . The strength group lost more body fat ( 2.8 + /- 2.0 versus 1.3 + /- 2.0 kg , P < 0.01 ) , tended to gain more lean tissue ( 1.5 + /- 2.3 versus 0.5 + /- 1.2 kg , P < 0.10 ) , and had greater improvements in treadmill time ( 2.3 + /- 1.3 versus 1.2 + /- 1.0 minute , P < 0.02 ) than did the flexibility group . Improvements in joint flexibility were similar for each group . None of the subjects had evidence of cardiac ischemia or arrhythmia during the training sessions . CONCLUSIONS Medically supervised high-intensity strength training is well tolerated when added to the aerobic training of cardiac rehabilitation programs and allows patients to aggressively gain the strength and endurance they will need to complete daily living tasks at lower perceived efforts . Strength training also reduces cardiac risk factors by improving body composition and maximum treadmill exercise time BACKGROUND Coronary artery surgery improves symptoms and prognosis in patients with angina . Aerobic exercise rehabilitation improves exercise capacity and prognosis in cardiac patients . Strength exercise training has not been extensively studied . DESIGN We studied the effects of 6 months aerobic and strength exercise training after coronary artery surgery in 81 men , mean age 57 years . RESULTS Treadmill time(s ) increased by 130.3 ( 95 % confidence interval 46.4 to 214.2 ) in the aerobic group ; by 83.1 ( 0.9 to 165.3 ) in the strength group , and by 34.3 ( -1 to 69.6 ) in the control group ( P = 0.04 , control versus aerobic ) after 3 months ; and by 196.4 ( 112.2 to 280.7 ) in the aerobic group , by 122.7 ( 37.7 to 207.6 ) in the strength group and by 27 ( -40.4 to 94.4 ) in the control group ( P = 0.002 , control versus aerobic , and P = 0.03 control versus strength ) after 6 months . The level of fitness improved more in the strength-trained group , and there was a minor reduction in body weight and degree of fatness . There were no changes in lipoprotein levels . Aerobic exercise training causes early and sustained benefit in treadmill exercise capacity , while the effects of strength exercise training are later in onset . Exercise training alone did not influence lipid levels . CONCLUSION Cardiac rehabilitation programmes should be comprehensive , including advice on diet and other risk factor modifications in addition to exercise sessions involving aerobic and strength training elements |
2,337 | 31,050,803 | Compared with IPT-SP , moderate certainty evidence indicated that women who received IPT-DP had significantly lower risks of clinical malaria during pregnancy .
High certainty evidence showed intermittent screening and treatment with DP did not reduce placental malaria or maternal parasitemia at delivery .
Effect of DP on low birth weight and adverse birth outcomes was minimal .
Moderate certainty evidence suggests that IPT-DP may reduce maternal and placental malaria compared with IPT-SP , and monthly DP is more effective than SP in reducing placental malaria . | BACKGROUND Intermittent preventive treatment ( IPT ) with sulphadoxine-pyrimethamine ( SP ) is recommended for preventing maternal and fetal effects of malaria in pregnancy .
Increasing parasite resistance to SP has necessitated the search for an alternative medication .
OBJECTIVE To compare dihydroartemisinin-piperaquine ( DP ) and sulphadoxine-pyrimethamine in preventing malaria during pregnancy . | BACKGROUND Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited , particularly among women who live in sub-Saharan Africa . METHODS We conducted a multicenter , r and omized , open-label trial of treatments for malaria in pregnant women in four African countries . A total of 3428 pregnant women in the second or third trimester who had falciparum malaria ( at any parasite density and regardless of symptoms ) were treated with artemether-lumefantrine , amodiaquine-artesunate , mefloquine-artesunate , or dihydroartemisinin-piperaquine . The primary end points were the polymerase-chain-reaction (PCR)-adjusted cure rates ( i.e. , cure of the original infection ; new infections during follow-up were not considered to be treatment failures ) at day 63 and safety outcomes . RESULTS The PCR-adjusted cure rates in the per- protocol analysis were 94.8 % in the artemether-lumefantrine group , 98.5 % in the amodiaquine-artesunate group , 99.2 % in the dihydroartemisinin-piperaquine group , and 96.8 % in the mefloquine-artesunate group ; the PCR-adjusted cure rates in the intention-to-treat analysis were 94.2 % , 96.9 % , 98.0 % , and 95.5 % , respectively . There was no significant difference among the amodiaquine-artesunate group , dihydroartemisinin-piperaquine group , and the mefloquine-artesunate group . The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups , although the absolute difference was within the 5-percentage-point margin for equivalence . The unadjusted cure rates , used as a measure of the post-treatment prophylactic effect , were significantly lower in the artemether-lumefantrine group ( 52.5 % ) than in groups that received amodiaquine-artesunate ( 82.3 % ) , dihydroartemisinin-piperaquine ( 86.9 % ) , or mefloquine-artesunate ( 73.8 % ) . No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups . Drug-related adverse events such as asthenia , poor appetite , dizziness , nausea , and vomiting occurred significantly more frequently in the mefloquine-artesunate group ( 50.6 % ) and the amodiaquine-artesunate group ( 48.5 % ) than in the dihydroartemisinin-piperaquine group ( 20.6 % ) and the artemether-lumefantrine group ( 11.5 % ) ( P<0.001 for comparison among the four groups ) . CONCLUSIONS Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest posttreatment prophylaxis , whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile . ( Funded by the European and Developing Countries Clinical Trials Partnership and others ; Clinical Trials.gov number , NCT00852423 . ) BACKGROUND Intermittent treatment with sulfadoxine-pyrimethamine is widely recommended for the prevention of malaria in pregnant women in Africa . However , with the spread of resistance to sulfadoxine-pyrimethamine , new interventions are needed . METHODS We conducted a double-blind , r and omized , controlled trial involving 300 human immunodeficiency virus (HIV)-uninfected pregnant adolescents or women in Ug and a , where sulfadoxine-pyrimethamine resistance is widespread . We r and omly assigned participants to a sulfadoxine-pyrimethamine regimen ( 106 participants ) , a three-dose dihydroartemisinin-piperaquine regimen ( 94 participants ) , or a monthly dihydroartemisinin-piperaquine regimen ( 100 participants ) . The primary outcome was the prevalence of histopathologically confirmed placental malaria . RESULTS The prevalence of histopathologically confirmed placental malaria was significantly higher in the sulfadoxine-pyrimethamine group ( 50.0 % ) than in the three-dose dihydroartemisinin-piperaquine group ( 34.1 % , P=0.03 ) or the monthly dihydroartemisinin-piperaquine group ( 27.1 % , P=0.001 ) . The prevalence of a composite adverse birth outcome was lower in the monthly dihydroartemisinin-piperaquine group ( 9.2 % ) than in the sulfadoxine-pyrimethamine group ( 18.6 % , P=0.05 ) or the three-dose dihydroartemisinin-piperaquine group ( 21.3 % , P=0.02 ) . During pregnancy , the incidence of symptomatic malaria was significantly higher in the sulfadoxine-pyrimethamine group ( 41 episodes over 43.0 person-years at risk ) than in the three-dose dihydroartemisinin-piperaquine group ( 12 episodes over 38.2 person-years at risk , P=0.001 ) or the monthly dihydroartemisinin-piperaquine group ( 0 episodes over 42.3 person-years at risk , P<0.001 ) , as was the prevalence of parasitemia ( 40.5 % in the sulfadoxine-pyrimethamine group vs. 16.6 % in the three-dose dihydroartemisinin-piperaquine group [ P<0.001 ] and 5.2 % in the monthly dihydroartemisinin-piperaquine group [ P<0.001 ] ) . In each treatment group , the risk of vomiting after administration of any dose of the study agents was less than 0.4 % , and there were no significant differences among the groups in the risk of adverse events . CONCLUSIONS The burden of malaria in pregnancy was significantly lower among adolescent girls or women who received intermittent preventive treatment with dihydroartemisinin-piperaquine than among those who received sulfadoxine-pyrimethamine , and monthly treatment with dihydroartemisinin-piperaquine was superior to three-dose dihydroartemisinin-piperaquine with regard to several outcomes . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ; Clinical Trials.gov number , NCT02163447 . ) Background Artemisinin combination therapies ( ACTs ) are currently the preferred option for treating uncomplicated malaria . Dihydroartemisinin-piperaquine ( DHA-PQP ) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children . Methodology /Principal Findings The non-inferiority of DHA-PQP versus artemether-lumefantrine ( AL ) in children 6–59 months old with uncomplicated P. falciparum malaria was tested in five African countries ( Burkina Faso , Kenya , Mozambique , Ug and a and Zambia ) . Patients were r and omised ( 2∶1 ) to receive either DHA-PQP or AL . Non-inferiority was assessed using a margin of −5 % for the lower limit of the one-sided 97.5 % confidence interval on the treatment difference ( DHA-PQP vs. AL ) of the day 28 polymerase chain reaction ( PCR ) corrected cure rate . Efficacy analysis was performed in several population s , and two of them are presented here : intention-to-treat ( ITT ) and enlarged per- protocol ( ePP ) . 1553 children were r and omised , 1039 receiving DHA-PQP and 514 AL . The PCR-corrected day 28 cure rate was 90.4 % ( ITT ) and 94.7 % ( ePP ) in the DHA-PQP group , and 90.0 % ( ITT ) and 95.3 % ( ePP ) in the AL group . The lower limits of the one-sided 97.5 % CI of the difference between the two treatments were −2.80 % and −2.96 % , in the ITT and ePP population s , respectively . In the ITT population , the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55 % ( 95 % CI : 11.35%–15.76 % ) for DHA-PQP vs 24.00 % ( 95 % CI : 20.11%–27.88 % ) for AL ( p<0.0001 ) . Conclusions / Significance DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity setting s , and shows a comparable safety profile . The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group , indicating a longer post-treatment prophylactic effect . Trial Registration Controlled-trials.com IS RCT 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 In Africa , most plasmodium infections during pregnancy remain asymptomatic , yet are associated with maternal anemia and low birthweight . WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine ( IPTp-SP ) . However , sulfadoxine-pyrimethamine ( SP ) efficacy is threatened by high-level parasite resistance . We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests ( RDTs ) and treatment of RDT-positive women with dihydroartemisinin-piperaquine ( DP ) as an alternative strategy to IPTp-SP . Methods and Findings This was an open-label , two-arm individually r and omized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance . The intervention consisted of three or four scheduled visits in the second and third trimester , 4 to 6 wk apart . Women in the IPTp-SP arm received SP at each visit . Women in the intermittent screening and treatment in pregnancy with DP ( ISTp-DP ) arm were screened for malaria at every visit and treated with DP if RDT-positive . The primary outcomes were adverse live birth outcome ( composite of small for gestational age , low birthweight [ < 2,500 g ] , or preterm birth [ < 37 wk ] ) in paucigravidae ( first or second pregnancy ) and maternal or placental plasmodium infection at delivery in multigravidae ( third pregnancy or higher ) . Analysis was by intention to treat . Between 21 July 2011 and 18 March 2013 , 1,873 women were recruited ( 1,155 paucigravidae and 718 multigravidae ) . The prevalence of adverse live birth outcome was similar in the ISTp-DP ( 29.9 % ) and IPTp-SP ( 28.8 % ) arms ( risk difference = 1.08 % [ 95 % CI −3.25 % to 5.41 % ] ; all women : relative risk [ RR ] = 1.04 [ 95 % CI 0.90–1.20 ] , p = 0.625 ; paucigravidae : RR = 1.10 [ 95 % CI 0.92–1.31 ] , p = 0.282 ; multigravidae : RR = 0.92 [ 95 % CI 0.71–1.20 ] , p = 0.543 ) . The prevalence of malaria at delivery was higher in the ISTp-DP arm ( 48.7 % versus 40.8 % ; risk difference = 7.85 % , [ 95 % CI 3.07%–12.63 % ] ; all women : RR = 1.19 [ 95 % CI 1.07–1.33 ] , p = 0.007 ; paucigravidae : RR = 1.16 [ 95 % CI 1.04–1.31 ] , p = 0.011 ; multigravidae : RR = 1.29 [ 95 % CI 1.02–1.63 ] , p = 0.037 ) . Fetal loss was more common with ISTp-DP ( 2.6 % versus 1.3 % ; RR = 2.06 [ 95 % CI 1.01–4.21 ] , p = 0.046 ) and highest among non-DP-recipients ( 3.1 % ) in the ISTp-DP arm . Limitations included the open-label design . Conclusions Scheduled screening for malaria parasites with the current generation of RDTs three to four times during pregnancy as part of focused antenatal care was not superior to IPTp-SP in this area with high malaria transmission and high SP resistance and was associated with higher fetal loss and more malaria at delivery . Trial Registration Pan African Clinical Trials Registry PACTR201103000280319 ; IS RCT N Registry IS RCT To define an effective and deliverable antimalarial regimen for use during pregnancy , pregnant women at highest risk of malaria ( those in their first or second pregnancy ) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and /or sulfadoxine-pyrimethamine ( SP ) . Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis ( CQ/CQ ) for at least 45 days prior to delivery , 32 % had placental malaria infection , compared with 26 % of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis ( SP/CQ ) , and only 9 % of 71 pregnant women who received a two-dose SP regimen ( SP/SP ; given once during the second trimester and repeated at the beginning of the third trimester ) ( P = 0.006 , by chi-square test ) . During the peak transmission season from April to July , 47 % of the women who received CQ/CQ had placental malaria infection at delivery , as compared with 37 % of the women who received SP/CQ , and 10 % of women who received SP/SP ( P = 0.004 , by chi-square test ) . Among women in their first or second pregnancy , two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery ABSTRACT The tolerability , safety , and disposition of dihydroartemisinin ( DHA ) and piperaquine ( PQ ) were assessed in 32 pregnant ( second/third trimester ) and 33 nonpregnant Papua New Guinean women r and omized to adult treatment courses of DHA-PQ ( three daily doses ) or sulfadoxine-pyrimethamine (SP)-PQ ( three daily PQ doses , single dose of SP ) . All dose adminstrations were observed , and subjects fasted for 2 h postdose . Plasma PQ was assayed by using high-performance liquid chromatography , and DHA was assessed by using liquid chromatography-mass spectrometry . Compartmental pharmacokinetic models were developed using a population -based approach . Both regimens were well tolerated . There was an expected increase in the rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment . Two pregnant and two nonpregnant women had Plasmodium falciparum parasitemia which cleared within 48 h , and no other subject became slide positive for malaria during 42 days of follow-up . Of 30 pregnant women followed to delivery , 27 ( 90 % ) delivered healthy babies and 3 ( 10 % ) had stillbirths ; these obstetric outcomes are consistent with those in the general population . The area under the plasma PQ concentration-time curve ( AUC0–∞ ) was lower in the pregnant patients ( median [ interquartile range ] , 23,721 μg · h/liter [ 21,481 to 27,951 μg · h/liter ] versus 35,644 μg · h/liter [ 29,546 to 39,541 μg · h/liter ] ; P < 0.001 ) in association with a greater clearance relative to bioavailability ( 73.5 liters/h [ 69.4 to 78.4 ] versus 53.8 liters/h [ 49.7 to 58.2 ] ; P < 0.001 ) , but pregnancy did not influence the pharmacokinetics of DHA . The apparent pharmacokinetic differences between the present study and results from other studies of women with uncomplicated malaria that showed no effect of pregnancy on the AUC0–∞ of PQ and greater bioavailability may reflect differences in postdose fat intake , proportions of women with malaria , and /or racial differences in drug disposition Clara Menéndez and colleagues conducted an open-label r and omized controlled trial in HIV-negative pregnant women in Benin , Gabon , Mozambique , and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria . Please see later in the article for the Editors ' BACKGROUND Every year , more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences . The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance . We aim ed to assess the efficacy and safety of two alternative strategies : intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine , and intermittent preventive treatment with dihydroartemisinin-piperaquine . METHODS We did this open-label , three-group , r and omised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance . HIV-negative pregnant women between 16 and 32 weeks ' gestation were r and omly assigned ( 1:1:1 ) , via computer-generated permuted-block r and omisation ( block sizes of three , six , and nine ) , to receive intermittent screening and treatment with dihydroartemisinin-piperaquine , intermittent preventive treatment with dihydroartemisinin-piperaquine , or intermittent preventive treatment with sulfadoxine-pyrimethamine . Study participants , study clinic nurses , and the study coordinator were aware of treatment allocation , but allocation was concealed from study investigators , delivery unit nurses , and laboratory staff . The primary outcome was malaria infection at delivery , defined as a composite of peripheral or placental parasitaemia detected by placental histology , microscopy , or rapid diagnostic test . The primary analysis was by modified intention to treat . This study is registered with Clinical Trials.gov , number NCT01669941 . FINDINGS Between Aug 21 , 2012 , and June 19 , 2014 , we r and omly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine ( n=515 ) , intermittent preventive treatment with dihydroartemisinin-piperaquine ( n=516 ) , or intermittent preventive treatment with sulfadoxine-pyrimethamine ( n=515 ) ; 1368 ( 88 % ) women comprised the intention-to-treat population for the primary endpoint . Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group ( 15 [ 3 % ] of 457 women vs 47 [ 10 % ] of 459 women ; relative risk 0·32 , 95 % CI 0·18 - 0·56 ; p<0·0001 ) , but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group ( 57 [ 13 % ] of 452 women ; 1·23 , 0·86 - 1·77 ; p=0·26 ) . Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine , intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy ( 192·0 vs 54·4 events per 100 person-years ; incidence rate ratio [ IRR ] 0·28 , 95 % CI 0·22 - 0·36 ; p<0·0001 ) and clinical malaria during pregnancy ( 37·9 vs 6·1 events ; 0·16 , 0·08 - 0·33 ; p<0·0001 ) , whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection ( 232·0 events ; 1·21 , 1·03 - 1·41 ; p=0·0177 ) and clinical malaria ( 53·4 events ; 1·41 , 1·00 - 1·98 ; p=0·0475 ) . We recorded 303 maternal and infant serious adverse events , which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group . INTERPRETATION At current levels of rapid diagnostic test sensitivity , intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission . However , dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment . Future studies should investigate the efficacy , safety , operational feasibility , and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine . FUNDING The Malaria in Pregnancy Consortium , which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine |
2,338 | 31,860,457 | Interpretation Marked differences exist between antipsychotics in terms of metabolic side-effects , with olanzapine and clozapine exhibiting the worst profiles and aripiprazole , brexpiprazole , cariprazine , lurasidone , and ziprasidone the most benign profiles .
Increased baseline weight , male sex , and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change , and improvements in psychopathology are associated with metabolic disturbance . | Summary Background Antipsychotic treatment is associated with metabolic disturbance .
However , the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear .
Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain .
We aim ed to compare and rank antipsychotics on the basis of their metabolic side-effects , identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation , and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment . | OBJECTIVE Antipsychotics , such as aripiprazole and risperidone , are often used to treat individuals with schizophrenia . The efficacy as well as safety of aripiprazole in Western population s has been described . The objective of this study is to investigate the efficacy , safety , and tolerability of aripiprazole and risperidone in Chinese Han schizophrenia subjects in mainl and China . METHOD The 6-week , double-blind , r and omized , parallel study was conducted in 5 medical centers in mainl and China from November 2007 to March 2011 . A total of 279 subjects with a primary DSM-IV diagnosis of schizophrenia were r and omly assigned ( with a r and omization ratio of 1:1 ) to aripiprazole ( n=139 ) or risperidone ( n=140 ) . Efficacy measurements included the Positive and Negative Syndrome Scale ( PANSS ) total , positive , negative and general psychopathology subscale scores , and Clinical Global Impressions-Severity of Illness ( CGI-S ) , and Improvement scale scores . Extrapyramidal symptoms ( EPS ) , weight gain , serum prolactin level , QTc interval , and self-reported adverse events were also assessed as measures of safety and tolerability . RESULTS Both the aripiprazole and risperidone groups showed statistically significant improvement of PANSS total , positive , negative , general psychopathology subscale scores , and CGI-S scores from baseline to the endpoint ( all p<0.01 ) . Significant improvement was noted in the first week for both treatment groups . There were no significant differences in efficacy measurements between the two treatment groups . Mean change of PANSS total scores from baseline to the endpoint was -26.8±18.1 for aripiprazole and -30.0±17.7 for risperidone , ( p=0.1475 ) . The responder rate was 71 % ( n=99 ) and 76 % ( n=107 ) for aripiprazole and risperidone , respectively , ( p=0.323 ) . The incidences of EPS were similar in the aripiprazole ( 25 % , n=35 ) and risperidone groups ( 24 % , n=34 ) , respectively ( p=0.757 ) . No clinical ly meaningful effects on QTc interval , QRS duration , or PR interval were observed in either treatment groups . However , the incidence of clinical ly significant weight gain ( p=0.0118 ) and hyperprolactinemia ( p<0.001 ) in the aripiprazole group was significantly lower than in the risperidone group . CONCLUSION The study demonstrated that aripiprazole , as well as risperidone , had rapid and persistent efficacy for psychotic symptoms from the first week of therapy . There may be poor efficacy for aripiprazole compared with risperidone for overall improvement , but there were no significant differences in this study . Aripiprazole showed good tolerability with less weight gain and hyperprolactinemia compared with risperidone . The overall efficacy and safety of aripiprazole in Chinese Han schizophrenia subjects were similar to that reported in Western population OBJECTIVE The objective of this multicenter , international study was to evaluate safety and tolerability of paliperidone extended-release ( ER ) tablets in elderly ( age > or = 65 years ) patients with schizophrenia . The authors conducted a 6-week , double-blind , r and omized , placebo-controlled , optional 24-week open-label extension study . Interventions consisted of flexible , once-daily doses of paliperidone ER ( 3 - 12 mg/day ; 6-mg starting dose , adjusted in 3-mg dose increments ) or placebo ( 2:1 ) during double-blind treatment and paliperidone ER only during open-label treatment . Measurements included adverse events , laboratory tests , physical examinations , 12-lead electrocardiograms , movement disorder rating scales , Positive and Negative Syndrome Scale , and Clinical Global Impression scale . The study was not powered to show statistical differences . RESULTS Patients ( N = 114 ) were predominantly female ( 73 % ) ; mean age was 70 years ( double-blind phase ) . Concomitant disease presence was consistent with that of an older population . During the double-blind phase , discontinuation rates result ing from adverse events were similar between groups ( paliperidone ER : 7 % , placebo : 8 % ) as were incidences of treatment-emergent adverse events ( paliperidone ER : 67 % , placebo : 71 % ) . Serious adverse events occurred in 3 % of the paliperidone ER- and 8 % of the placebo-treated patients . Elevated prolactin levels occurred in approximately one half of patients . No prolactin- or glucose treatment-related adverse events or noteworthy mean changes in body weight ( 0 kg [ st and ard deviation : 2.1 ] and 0 kg [ st and ard deviation : 2.3 ] for paliperidone ER and placebo , respectively ) were observed . Safety and tolerability results in the extension were consistent with the shorter-term results . Efficacy measures did not show consistent statistical improvement between treatment groups . CONCLUSION Paliperidone ER ( 3 - 12 mg/day ) treatment over a 30-week period was generally well-tolerated and may improve symptom severity in elderly patients with schizophrenia OBJECTIVE To evaluate aripiprazole once-monthly ( AOM ) , a long-acting injectable suspension of aripiprazole , as acute treatment in patients with schizophrenia ( DSM-IV-TR ) . METHOD Adults experiencing an acute psychotic episode were r and omized to 12 weeks of double-blind treatment with AOM 400 mg or placebo ( October 2012-August 2013 ) . The primary efficacy outcome was change from baseline to endpoint ( week 10 ) in Positive and Negative Syndrome Scale ( PANSS ) total score . The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . Secondary efficacy outcomes included change from baseline in PANSS positive and negative subscale and Personal and Social Performance Scale ( PSP ) scores . The study took place from October 2012 through August 2013 . RESULTS Patients ( N = 340 ; 79 % male , 66 % black ) were r and omized to AOM ( n = 168 ) or placebo ( n = 172 ) . Least squares ( LS ) mean change from baseline to endpoint ( week 10 ) favored AOM versus placebo in PANSS total ( treatment difference , -15.1 [ 95 % CI , -19.4 to -10.8 ] ; P < .0001 ) and CGI-S ( treatment difference , -0.8 [ 95 % CI , -1.1 to -0.6 ] ; P < .0001 ) scores , as it did at all other timepoints through 12 weeks ( all P ≤ .0005 ) . LS mean change from baseline in PANSS positive and negative subscale and PSP scores favored AOM versus placebo ( P < .0001 ) . Common ( > 10 % ) treatment-emergent adverse events ( AOM vs. placebo ) were increased weight ( 16.8 % vs 7.0 % ) , headache ( 14.4 % vs. 16.3 % ) , and akathisia ( 11.4 % vs 3.5 % ) . CONCLUSIONS Symptoms and functioning improved with AOM 400 mg versus placebo in patients with acute schizophrenia , with acceptable safety and tolerability . These data suggest that AOM 400 mg is a viable treatment option for patients experiencing an acute schizophrenia episode . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01663532 OBJECTIVE The efficacy , safety , and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia . METHOD This was a multicenter , r and omized , double-blind , placebo-controlled study . Patients with schizophrenia experiencing an acute exacerbation were r and omly assigned to daily brexpiprazole at a dosage of 0.25 , 2 , or 4 mg or placebo ( 1:2:2:2 ) for 6 weeks . Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( primary endpoint measure ) , Clinical Global Impressions Scale ( CGI ) severity score ( key secondary endpoint measure ) , and other efficacy and tolerability measures . RESULTS The baseline overall mean PANSS total score was 95.2 , and the CGI severity score was 4.9 . Study completion rates were 62.2 % , 68.1 % , and 67.2 % for patients in the 0.25- , 2- , and 4-mg brexpiprazole groups , respectively , versus 59.2 % in the placebo group . At week 6 , compared with placebo , brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score ( treatment differences : -8.72 and -7.64 , respectively ) and CGI severity score ( treatment differences : -0.33 and -0.38 ) . The most common treatment-emergent adverse event for brexpiprazole was akathisia ( 2 mg : 4.4 % ; 4 mg : 7.2 % ; placebo : 2.2 % ) . Weight gain with brexpiprazole was moderate ( 1.45 and 1.28 kg for 2 and 4 mg , respectively , versus 0.42 kg for placebo at week 6 ) . There were no clinical ly or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings . CONCLUSIONS Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation Objective : The objective of this study was to evaluate the short-term efficacy and safety of the atypical antipsychotic agent lurasidone in the treatment of schizophrenia . Methods : In this phase II , r and omized , double-blind , placebo-controlled study , hospitalized adult patients diagnosed with schizophrenia and experiencing an acute exacerbation of psychotic symptoms were r and omly assigned to 6 weeks of fixed-dose lurasidone 20 mg/day ( n = 71 ) , lurasidone 40 mg/day ( n = 67 ) , lurasidone 80 mg/day ( n = 71 ) , haloperidol 10 mg/day ( n = 72 , included to test for assay sensitivity ) , or placebo ( n = 72 ) . Efficacy was assessed using the brief psychiatric rating scale , positive and negative syndrome scale , and clinical global impression-severity . Safety assessment s included incidence of adverse events and clinical laboratory measures . Results : Numerical improvement was observed from baseline to week 6 ( last observation carried forward ) on all efficacy measures in all treatment groups ; however , no statistically significant differences were noted between any lurasidone group and placebo , or between haloperidol and placebo . The most common adverse events in lurasidone-treated patients , with an incidence of at least 10 % ( dose groups combined ) and greater than placebo , were sedation ( 15.3 % ) , dyspepsia ( 13.4 % ) , nausea ( 13.4 % ) , akathisia ( 12.4 % ) , and vomiting ( 10.5 % ) ; for haloperidol , the most common adverse events ( incidence ⩾ 10 % and greater than placebo ) were extrapyramidal disorder ( 20.8 % ) , sedation ( 19.4 % ) , akathisia ( 19.4 % ) , dystonia ( 15.3 % ) , insomnia ( 13.9 % ) , and somnolence ( 12.5 % ) . Lurasidone was associated with minimal changes in weight , metabolic parameters , and prolactin levels . Conclusions : None of the lurasidone groups separated from placebo in this clinical study of patients with acute schizophrenia . In addition , haloperidol , which was included for assay sensitivity , did not separate from placebo , result ing in a failed study . Possible reasons for the lack of assay sensitivity in this study include the use of multiple active treatment arms and the relatively large placebo response . Consistent with other studies , lurasidone was generally safe and well tolerated , with minimal effects on weight or metabolic parameters Paliperidone palmitate is a long-acting injectable antipsychotic agent . This 13-week , multicenter , r and omized ( 1 : 1 : 1 : 1 ) , double-blind , parallel-group study evaluated the efficacy , safety , and tolerability of fixed 25 , 50 , and 100 milligram equivalent ( mg equiv . ) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8 , then every 4 weeks ( days 36 and 64 ) in 518 adult patients with schizophrenia . The intent-to-treat analysis set ( N=514 ) was 67 % men and 67 % White , with a mean age of 41 years . All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale ( PANSS ) total score ( primary efficacy measure ; 25 and 50 mg equiv . , p=0.02 ; 100 mg equiv . , p<0.001 ) , as well as Clinical Global Impression Severity scores ( p⩽0.006 ) and PANSS negative and positive symptom Marder factor scores ( p⩽0.04 ) . The Personal and Social Performance scale showed no significant difference between treatment groups . The overall incidence of treatment-emergent adverse events was similar between groups . Parkinsonism , the most frequently reported extrapyramidal symptom , was reported at similar rates for placebo ( 5 % ) and paliperidone palmitate ( 5–6 % across doses ) . The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment . Investigator-evaluated injection-site pain , swelling , redness , and in duration were similar across treatment groups ; scores for patient-evaluated injection-site pain ( visual analog scale ) were similar across groups and diminished with time . All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated , both locally and systemically . Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia Rationale There is an unmet need in the treatment of schizophrenia for effective medications with fewer adverse effects . Objective This study aims to evaluate the efficacy and safety of lurasidone , an atypical antipsychotic , for the treatment of schizophrenia . Methods Patients with an acute exacerbation of schizophrenia were r and omized to 6 weeks of double-blind treatment with once-daily , fixed-dose lurasidone 40 mg ( N = 50 ) , lurasidone 120 mg ( N = 49 ) , or placebo ( N = 50 ) . The primary efficacy measure was mean change from baseline to day 42 ( last observation carried forward ) in the Brief Psychiatric Rating Scale derived ( BPRSd ) from the Positive and Negative Syndrome Scale ( PANSS ) . Results Mean change in BPRSd was significantly greater in patients receiving lurasidone 40 and 120 mg/day versus placebo ( −9.4 and −11.0 versus −3.8 ; p = 0.018 and 0.004 , respectively ) . Treatment with lurasidone 120 mg/day was superior to placebo across all secondary measures , including PANSS total ( p = 0.009 ) , PANSS positive ( p = 0.005 ) , PANSS negative ( p = 0.011 ) , and PANSS general psychopathology ( p = 0.023 ) subscales and Clinical Global Impression of Severity ( CGI-S ; p = 0.001 ) . Treatment with lurasidone 40 mg/day was superior to placebo on the PANSS positive subscale ( p = 0.018 ) and CGI-S ( p = 0.002 ) . The most common adverse events for patients receiving lurasidone were nausea ( 16.2 versus 4.0 % for placebo ) and sedation ( 16.2 versus 10.0 % for placebo ) . Minimal changes in weight , cholesterol , triglyceride , and glucose levels were observed . Conclusions In this study , which was limited by a relatively high discontinuation rate , lurasidone provided effective treatment for patients with acute exacerbation of chronic schizophrenia and had minimal effects on weight and metabolic parameters OBJECTIVE To assess the effect of dose increase in adult patients with schizophrenia who demonstrate inadequate initial response to st and ard-dose lurasidone and to evaluate the efficacy of low-dose lurasidone in adult patients with schizophrenia . METHODS In this r and omized , double-blind , placebo-controlled study conducted between May 2013 and June 2014 , hospitalized patients with acute schizophrenia ( DSM-IV-TR criteria ) were r and omly assigned to double-blind treatment with lurasidone 20 mg/d ( n = 101 ) , lurasidone 80 mg/d ( n = 199 ) , or placebo ( n = 112 ) . Nonresponders to lurasidone 80 mg/d ( Positive and Negative Syndrome Scale [ PANSS ] score decrease < 20 % ) at 2 weeks were re-r and omized to lurasidone 80 mg/d or 160 mg/d for the remaining 4 weeks of the study . The primary outcome measure was change from baseline to week 6 in PANSS total score . RESULTS In nonresponders to lurasidone 80 mg/d ( n = 95 ) , dose increase to 160 mg/d at week 2 significantly reduced PANSS total score at week 6 study endpoint compared with continuing 80 mg/d ( -16.6 vs -8.9 ; P < .05 [ effect size = 0.52 ] ) . While a comparable magnitude of improvement was observed in Clinical Global Impression-Severity ( CGI-S ) score from week 2 to week 6 endpoint for lurasidone 160 mg/d versus 80 mg/d ( -1.0 vs -0.6 ; effect size = 0.44 ) , the difference was not statistically significant ( P = .052 ) . Patients receiving lurasidone 20 mg/d did not demonstrate significant improvement compared with placebo at week 6 in PANSS total ( -17.6 vs -14.5 ; P = .26 ) or CGI-S ( -0.93 vs -0.73 ; P = .17 ) scores . Few dose-related adverse effects associated with lurasidone were observed . CONCLUSIONS In adult patients with schizophrenia demonstrating nonresponse to 2 weeks of treatment with lurasidone 80 mg/d , dose increase to 160 mg/d result ed in significant symptom improvement compared with continuing lurasidone 80 mg/d . Lurasidone 20 mg/d was not associated with significant improvement in psychotic symptoms in adult patients with schizophrenia . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01821378 OBJECTIVE Evaluate the efficacy and safety of asenapine 2.5 mg twice daily ( bid ; n=97 ) or 5 mg bid ( n=113 ) versus placebo ( n=101 ) in adults with acute exacerbation of schizophrenia . METHODS Adults with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision ( DSM-IV-TR ) schizophrenia diagnosis were r and omized to asenapine 2.5 mg bid , 5 mg bid , placebo , or olanzapine 15 mg once daily . The primary objective was to test superiority of asenapine versus placebo as measured by the change from baseline to day 42 in the Positive and Negative Syndrome Scale ( PANSS ) total score . The key safety objective was to evaluate weight change in asenapine versus olanzapine at day 42 . RESULTS The primary efficacy endpoint was met ; the difference in least squares mean change from baseline to day 42 in PANSS total score between asenapine 5 mg bid and placebo was -5.5 points ( unadjusted 95 % CI : -10.1 , -1.0 ; multiplicity adjusted P=0.0356 ) . Neither asenapine 2.5 mg bid nor olanzapine 15 mg were superior to placebo . Both asenapine groups demonstrated significantly less weight gain than olanzapine at day 42 . Significantly higher incidences of oral hypoesthesia and dysgeusia ( combined ) for asenapine 2.5 mg bid ( 5.2 % vs 0.0 % ; P=0.0217 ) and 5 mg bid ( 7.1 % vs 0.0 % ; P=0.0033 ) were observed versus placebo . There were no significant differences between asenapine and placebo for insomnia , extrapyramidal symptoms , akathisia , dizziness , or combination of somnolence/sedation/hypersomnia . CONCLUSION This study supports previous efficacy and safety findings of asenapine ; asenapine 5 mg bid is the lowest effective dose in adults with schizophrenia . Asenapine was associated with significantly less weight gain than olanzapine at day 42 This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate ( approved in the USA , August 2009 ) for adult patients with acutely exacerbated schizophrenia . The patients ( N = 652 ) were r and omly assigned ( 1:1:1:1 ) to paliperidone palmitate at 25 , 100 , or 150 mg eq. or placebo in this 13-week double-blind study . The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or muscle on day 8 and then once monthly ( days 36 and 64 ) . No oral supplementation was used . Target plasma levels were achieved by day 8 in all paliperidone palmitate groups . The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly ( P ≤ 0.034 ) in all the paliperidone palmitate dose-groups versus placebo . Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle . Common treatment-emergent adverse events ( ≥2 % of patients in any of the treatment groups ) that occurred more frequently in the total paliperidone palmitate group versus the placebo group ( with ≥1 % difference ) were injection-site pain ( 7.6 % vs 3.7 % ) , dizziness ( 2.5 % vs 1.2 % ) , sedation ( 2.3 % vs 0.6 % ) , pain in the extremity ( 1.6 % vs 0.0 % ) , and myalgia ( 1.0 % vs 0.0 % ) . The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range ( 25 , 100 , or 150 mg eq. ) in adult patients with acutely exacerbated schizophrenia . Abbreviations : BMI - body mass index , CGI-S - Clinical Global Impression-Severity , EPS - extrapyramidal symptoms , ER - extended release , ITT - intent-to-treat , LAI - long-acting injectable , PANSS - Positive and Negative Syndrome Scale , PK - pharmacokinetic , PSP - Personal and Social Performance Scale , TEAE - treatment-emergent adverse events , VAS - Visual Analogue Schizophrenia is a chronic , complex and heterogeneous mental disorder , with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain . These pathological features manifest behaviorally as positive symptoms ( including hallucinations , delusions and thought disorder ) , negative symptoms ( such as social withdrawal , apathy and emotional blunting ) and other psychopathological symptoms ( such as psychomotor retardation , lack of insight , poor attention and impulse control ) . Altered glutamate neurotransmission has for decades been linked to schizophrenia , but all commonly prescribed antipsychotics act on dopamine receptors . LY404039 is a selective agonist for metabotropic glutamate 2/3 ( mGlu2/3 ) receptors and has shown antipsychotic potential in animal studies . With data from rodents , we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine . To clinical ly test this mechanism , an oral prodrug of LY404039 ( LY2140023 ) was evaluated in schizophrenic patients with olanzapine as an active control in a r and omized , three-armed , double-blind , placebo-controlled study . Treatment with LY2140023 , like treatment with olanzapine , was safe and well-tolerated ; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo ( P < 0.001 at week 4 ) . Notably , patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation , extrapyramidal symptoms or weight gain . These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia OBJECTIVE The comparative efficacy of second-generation antipsychotics has yet to be fully eluci date d in patients with treatment-resistant schizophrenia . The objective of this study was to examine the efficacy and safety of sertindole , compared to risperidone , in this patient population . METHOD In this multicenter , phase 3 , r and omized , double-blind , parallel-group study , only patients with DSM-IV schizophrenia who had failed an adequate antipsychotic treatment within the previous 6 months and who had not responded positively to haloperidol during screening were eligible for enrollment . The primary efficacy variable was change in Positive and Negative Syndrome Scale ( PANSS ) from baseline to final assessment . Weekly assessment s included the PANSS , the Brief Psychiatric Rating Scale ( BPRS ) , the Scale for the Assessment of Negative Symptoms ( SANS ) , and the Clinical Global Impressions ( CGI ) scale . The study was conducted between June 1996 and April 1998 . RESULTS Of the 321 patients r and omly assigned to double-blind treatment , 217 patients completed the study ( sertindole , n/n = 142/216 [ 66 % ] ; risperidone , n/n = 75/105 [ 71 % ] ) . The main reason for withdrawal in both groups was ineffective therapy . The between-group difference in PANSS total score was not statistically significant and both groups showed improvement , with mean changes of -18.6 in the sertindole group and -20.9 in the risperidone group based on observed cases and -12.0 and -19.0 , respectively , based on the last-observation-carried-forward method for inputing missing data . There were no statistically significant differences between the groups in any of the secondary end points : PANSS positive and negative subscales , CGI scores , BPRS total scores and positive symptom subscale scores , and SANS total scores . Patients reported similar levels of adverse events and treatment-emergent adverse events ( TEAEs ) , except for extrapyramidal syndrome-related TEAEs , which were more common in the risperidone-treated group . Prolongation of the QTc interval was observed significantly more frequently with sertindole treatment . CONCLUSIONS Sertindole and risperidone are effective and well-tolerated in patients with treatment-resistant schizophrenia . Sertindole offers an alternative treatment option for refractory patients in Europe given its good EPS profile , favorable metabolic profile , and comparable efficacy to risperidone JNJ-37822681 is a novel , highly selective dopamine D₂ receptor antagonist characterized by a rapid dissociation rate from the dopamine D₂ receptor . This profile was hypothesized to confer antipsychotic efficacy and improved tolerability . In this 12-week study , the efficacy and safety of JNJ-37822681 were evaluated in patients with an acute exacerbation of schizophrenia , r and omly assigned ( 1:1:1:1:1 ) to JNJ-37822681 ( 10- , 20- or 30-mg bid ) , olanzapine ( 15 mg once-daily ) , or placebo ( for 6 weeks followed by olanzapine for 6 weeks ) . Of 498 r and omized patients , 298 ( 60 % ) completed the study . All JNJ-37822681 dose groups and the olanzapine group showed significantly greater reduction in PANSS total score from baseline to week 6 versus placebo ( all p-values < 0.001 ) . Least-squares adjusted mean changes from baseline to week 6 in PANSS total score were : -6.4 ( placebo ) ; -18.4 ( 10 mg JNJ-37822681 ) , -17.7 ( 20 mg JNJ-37822681 ) , -20.0 ( 30 mg JNJ-37822681 ) and -22.9 ( olanzapine ) . All JNJ-37822681 groups showed significant improvement versus placebo from baseline to week 6 in the PANSS subscales , Marder factors , Clinical Global Impression of Severity , and in the Subjective Well-Being on Neuroleptics scale ( all p-values < 0.05 ) . The most common treatment-emergent adverse events with JNJ-37822681 were insomnia ( 17 % ) and akathisia ( 13 % ) . Incidences of extrapyramidal symptoms were dose-related and were comparable for JNJ-37822681 10 mg bid and olanzapine groups . All JNJ-37822681 dose groups showed lesser weight gain compared with olanzapine . The efficacy and tolerability profile of the JNJ-37822681 10 mg bid was consistent with the study hypothesis Olanzapine is a potential new " atypical " antipsychotic agent . The double-blind acute phase of this study compared three dosage ranges of olanzapine ( 5 + /- 2.5 mg/day [ Olz-L ] , 10 + /- 2.5 mg/day [ Olz-M ] , 15 + /- 2.5 mg/day [ Olz-H ] ) to a dosage range of haloperidol ( 15 + /- 5 mg/day [ Hal ] ) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia . In overall symptomatology improvement ( Brief Psychiatric Rating Scale [BPRS]-total ) , Olz-M , Olz-H , and Hal were significantly superior to placebo . In positive symptom improvement ( BPRS-positive ) , Olz-M , Olz-H , and Hal were comparable and significantly superior to placebo . In negative symptom improvement ( Scale for the Assessment of Negative Symptoms [SANS]-composite ) , Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal . The most common treatment-emergent adverse events included somnolence , agitation , asthenia , and nervousness . No acute dystonia was observed with olanzapine . Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal , and akathisia occurred with Olz-H at approximately one-half the rate of Hal . Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To examine efficacy and safety of acute treatment with paliperidone palmitate in subjects with schizophrenia whose disease remained symptomatic despite recent treatment with oral risperidone . METHODS Post hoc analysis of a 13-week , double-blind , placebo-controlled study of subjects with symptomatic schizophrenia r and omized to paliperidone palmitate 39 , 156 , or 234 mg ( 25 , 100 , or 150 mg equivalents of paliperidone ) or placebo . Paliperidone palmitate subjects received a 234-mg day 1 dose , followed by their assigned dose on day 8 and monthly thereafter . Subjects treated with oral risperidone within 2 weeks before r and omization regardless of duration were included . ASSESSMENT S PANSS , CGI-S , PSP scores ; AEs . ANCOVA models with LOCF methodology evaluated treatment group differences . RESULTS 216 subjects received prior oral risperidone ( paliperidone palmitate 39 mg , n=53 ; 156 mg , n=58 ; 234 mg , n=48 ; placebo , n=57 ) . Median prior risperidone use was 22 days . Significant improvement was observed with paliperidone palmitate 156-mg or 234-mg versus placebo in least-squares mean ( SE ) score change at end point in PANSS total ( 156 mg , -15.8 [ 3.0 ] , p=0.0001 ; 234 mg , -17.6 [ 3.2 ] , p=0.0001 ) , CGI-S ( 156 mg , -0.9 [ 0.2 ] , p=0.0068 ; 234 mg , -1.1 [ 0.2 ] , p=0.0003 ) , and PSP ( 156 mg , 10.7 [ 2.3 ] , p=0.0061 ; 234 mg , 12.9 [ 2.4 ] , p=0.0009 ) . Most common AEs ( ≥10 % ) in any paliperidone palmitate group were insomnia , anxiety , and headache . CONCLUSIONS In subjects with schizophrenia who recently received oral risperidone but who remained symptomatic , acute treatment with monthly doses of 156-mg and 234-mg paliperidone palmitate significantly improved clinical symptoms , global illness ratings , and functioning compared with placebo , with no unexpected safety findings Background Pomaglumetad methionil ( LY2140023 monohydrate ) is a potent and highly selective agonist for the metabotropic glutamate mGluR2 and mGluR3 receptors . We present results of a pivotal clinical study H8Y-MC-HBBM assessing the efficacy of LY2140023 in improving symptoms as a monotherapy in patients with an acute exacerbation of schizophrenia . Methods Enrolled adult patients ( ages 18–65 ) with schizophrenia who had experienced an exacerbation of symptoms within 2 weeks prior to study entry . Patients ( N = 1013 ) were r and omized 2:2:2:1 to treatment with placebo , LY40 mg twice daily ( BID ) , LY80 mg BID , or risperidone ( RIS ) 2 mg BID for 6 weeks after a one-week blinded placebo lead-in . The primary outcome assessed change from baseline in the Positive and Negative Syndrome Scale ( PANSS ) total score in an overall schizophrenia population and a predefined sub population which excluded non-Hispanic white patients with the A/A genotype at the HTR2A SNP rs7330461 . Results Neither LY2140023 dose showed significant improvement compared to placebo on PANSS total in either population ( 1-sided p-value [ significance level ] , overall : LY40 , p = .154 [ 0.01 ] ; LY80 , p = .698 [ 0.01 ] , sub population : LY40 , p = .033 [ 0.0025 ] ; LY80 , p = .659 [ 0.0025 ] , MMRM analysis ) . RIS statistically separated from placebo in both population s ( p < .001 [ 0.05 ] ) . There were no statistically significant differences in the incidence of serious adverse events , and no seizures on LY2140023 . Conclusion LY2140023 treatment did not demonstrate efficacy in population s studied . Overall , LY2140023 treatment was generally well tolerated with no new adverse safety findings compared to previous trials . Further underst and ing of the role of glutamate as a therapeutic target in schizophrenia is needed . Clinical trials registration A Phase 2 , Multicenter , Double-Blind , Placebo-Controlled Comparator Study of 2 Doses of LY2140023 Versus Placebo in Patients With DSM-IV-TR Schizophrenia Clinical Trials.gov identifier : NCT01086748 BACKGROUND An urgent need exists for new treatments of schizophrenia that are effective against a broad range of symptoms and free of limiting safety issues . ITI-007 is a new molecular entity with a pharmacologic profile that combines dose-related monoamine modulation with phosphorylation of intracellular signaling proteins . METHODS A phase II r and omized , double-blind , placebo-controlled , and active-controlled trial was conducted at eight sites in the United States with r and omization of 335 acutely psychotic adults with schizophrenia . ITI-007 ( 60 mg and 120 mg ) , placebo , and risperidone , included for assay sensitivity , were evaluated as monotherapy for 4 weeks . The primary outcome measure was the Positive and Negative Syndrome Scale total score , with secondary analyses conducted on symptom subscales . RESULTS ITI-007 60 mg ( p = .017 , effect size = .4 ) and risperidone ( p = .013 , effect size = .4 ) demonstrated antipsychotic efficacy superiority over placebo on the primary end point . The results of secondary analyses reflected improvements in negative and depressive symptoms by ITI-007 60 mg . ITI-007 120 mg did not separate from placebo . However , both doses of ITI-007 were well tolerated in this patient population , as evidence d by low discontinuation and adverse event rates , and were associated with a benign metabolic profile as evidence d by significantly lower levels of prolactin , fasting glucose , total cholesterol , and triglycerides than risperidone . CONCLUSIONS The mechanistically novel investigational drug ITI-007 was effective for the treatment of schizophrenia and comparable with placebo on safety measures in this trial . Secondary analyses indicated that ITI-007 improved negative and depression symptoms and might have exp and ed therapeutic efficacy in comparison with current antipsychotic drugs Despite the availability of established antipsychotic agents for the treatment of schizophrenia , continued unmet needs exist for effective medications with lower adverse-effect burden . The present study evaluated the efficacy , safety , and tolerability of treatment with the atypical antipsychotic lurasidone for patients with an acute exacerbation of schizophrenia . Patients were r and omized to 6 weeks of double-blind treatment with lurasidone 40 mg/day , 80 mg/day , or 120 mg/day , or placebo . Changes in Positive and Negative Syndrome Scale ( PANSS ) scores were evaluated using mixed-model repeated- measures ( MMRM ) analysis . Vital signs , laboratory parameters , extrapyramidal symptoms , and electrocardiogram were assessed . Treatment with lurasidone 80 mg/day result ed in significantly greater improvement in PANSS total score compared with placebo ( -23.4 versus -17.0 ; p < 0.05 ) at study endpoint ( MMRM ) ; lurasidone 40 mg/day and 120 mg/day achieved clinical ly meaningful overall PANSS score reductions from baseline ( -19.2 and -20.5 ) , but not significant separation from placebo . Differences between all lurasidone groups and placebo for changes in laboratory parameters and electrocardiographic measures were minimal . Weight gain ≥ 7 % occurred in 8.2 % of patients receiving lurasidone and 3.2 % receiving placebo . Modest increases in prolactin ( median increase , 0.7 ng/mL ) and extrapyramidal symptoms were observed following treatment with lurasidone compared with placebo . Akathisia was the most commonly reported adverse event with lurasidone ( 17.6 % , versus 3.1 % with placebo ) . In this study , in which a large placebo response was observed , lurasidone 80 mg/day , but not 40 mg/day or 120 mg/day , was statistically superior to placebo in treating acute exacerbation of chronic schizophrenia . All lurasidone doses were generally well tolerated Abstract A double-blind , placebo-controlled , multicenter study , was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder . Patients were r and omized to receive ziprasidone 40 mg/day , 120 mg/day or placebo for 28 days . Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total , CGI-S , BPRS depression cluster and BPRS anergia cluster scores ( all P < 0.05 ) . Similarly , the percentages of patients classified as responders on the BPRS ( ≥30 % reduction ) and the CGI improvement ( score ≤2 ) were significantly greater with ziprasidone 120 mg/day compared with placebo ( P < 0.05 ) . The number of patients who experienced an adverse event was similar in all three treatment groups , and discontinuation due to adverse events was rare ( five of 91 ziprasidone-treated patients ) . The most frequently reported adverse events , that were more common in either ziprasidone group than in the placebo group , were dyspepsia , constipation , nausea and abdominal pain . There was a notably low incidence extrapyramidal side-effects ( including akathisia ) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain . Ziprasidone-treated patients were not clinical ly different from placebo-treated patients on the Simpson-Angus Rating scale , Barnes Akathisia scale and AIMS assessment s. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive , negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden Objective : Atypical antipsychotics are increasingly drugs of first choice in schizophrenia . Amisulpride , a new atypical antipsychotic , is reported to be effective for both positive and negative symptoms of schizophrenia in Western countries but Indian experience is limited . The aim of the present study was therefore to conduct a trial of amisulpride versus olanzapine in Indian schizophrenia patients . Methods : Eighty adult patients of either sex were r and omized to receive st and ard doses of the two drugs orally , in a single blind manner , for 12 weeks , with follow up at 4 and 8 weeks . Effectiveness was assessed by changes in scores on the Brief Psychiatric Rating Scale ( BPRS ) , Scale for Assessment of Positive Symptoms ( SAPS ) , Scale for Assessment of Negative Symptoms ( SANS ) , and physician-administered Clinical Global Impression ( CGI ) scale . Tolerability was assessed by treatment-emergent adverse drug reactions ( ADRs ) . Results : Evaluable were 39 patients on amisulpride and 38 on olanzapine . The groups were comparable at baseline with respect to demographics , illness duration and rating scores . Final BPRS score was lower for olanzapine ( 33.2 ± 9.44 ) than for amisulpride ( 37.7 ± 9.67 ) . SAPS and SANS scores and CGI rating improved individually in both arms but remained comparable between groups throughout the study period , but olanzapine reduced SAPS score to a greater extent . ADRs were encountered in 67.5 % and 47.5 % of patients ( p = 0.113 ) on amisulpride and olanzapine , respectively . Tremor and insomnia were more frequent with amisulpride , while olanzapine caused more weight gain and sedation . No serious ADRs occurred . Conclusions : Amisulpride , although comparable to olanzapine on some measures , did not match the improvement seen with the latter drug in BPRS and SAPS scores . Despite differences in ADR profiles , overall tolerability was satisfactory for both drugs . In Indian patients , amisulpride should therefore be an alternative to olanzapine to a limited extent , such as when weight gain and sedation are undesirable Sertindole is a non-sedating atypical antipsychotic effective in the management of schizophrenia and is associated with placebo-level incidence of extrapyramidal symptoms ( EPS ) . In this r and omized , double-blind , parallel-group , flexible-dose , multi-centre study , the efficacy and tolerability of sertindole was directly compared with another atypical antipsychotic in patients with schizophrenia . A total of 187 patients were r and omly assigned to treatment with sertindole ( 12–24 mg/day , n=98 ) or risperidone ( 4–10 mg/day , n=89 ) for 12 weeks . Although early termination reduced the power of the study , some significant between-group differences were evident . Sertindole reduced the mean Positive and Negative Syndrome Scale total scores to a greater extent than risperidone , and the difference reached statistical significance at endpoint for the Observed Cases ( OC ) data set . Moreover , sertindole was superior for the treatment of negative symptoms compared to risperidone ( P<0.05 , Last Observation Carried Forward and OC ) . Both treatment groups were similarly effective in improving Clinical Global Impression ( Severity and Improvement ) , the Drug Attitude Inventory and Global Assessment of Functioning scores . Sertindole and risperidone were both well tolerated . Numerically , fewer patients in the sertindole group ( 19 % ) reported EPS-related adverse events than in the risperidone group ( 28 % ) , although significantly more sertindole-treated patients reported QT prolongation and abnormal ejaculation volume ( P<0.05 ) . In conclusion , sertindole was well tolerated and demonstrated clinical ly relevant efficacy advantages over risperidone BACKGROUND Weight gain and changes in metabolic indicators associated with some antipsychotics may be related to symptom improvement and thus an unavoidable correlate of clinical benefit . METHODS Data from the CATIE schizophrenia trial comparing the effectiveness of perphenazine , olanzapine , risperidone , quetiapine and ziprasidone in a r and omized , double-blind , trial over 18 months were used to evaluate the relationship between percent change in body mass index ( BMI ) and change in total serum cholesterol and triglycerides with the Positive and Negative Syndrome Scale ( PANSS ) score . Analysis of covariance for observations at 3 months and a mixed effects model for all observations up to 18 months adjusted for potentially confounding variables were used to examine these associations . RESULTS In both models , there was a significant association ( p = 0.001 ) between change in PANSS total score and percent change in BMI , equating to a 0.28 and 0.21 point decrease in PANSS total score ( range 30 - 210 ) per 1 % increase in BMI respectively . Change in BMI accounted for 3 % or less of variance for change in PANSS scores . There was no evidence that the association of symptoms and weight gain differed across medications in spite of substantial differences in weight gain and other metabolic measures . Neither total serum cholesterol nor triglyceride levels displayed a significant association with change in PANSS . CONCLUSION The magnitude of the relationship between change in BMI and PANSS was too small to be clinical ly important , indicating that switching medications to one with less metabolic risk is unlikely to result in meaningful loss of clinical benefit OBJECTIVE To examine the change in Framingham risk score ( FRS ) arising from short-term treatment with ziprasidone or olanzapine . METHOD Hospitalized adults with a primary DSM-IV diagnosis of schizophrenia or schizo-affective disorder were r and omly assigned to 6 weeks of double-blind treatment with ziprasidone or olanzapine from November 21 , 1998 to September 28 , 2000 . Data on fasting lipid levels were collected at screening and endpoint , and blood pressure was measured at screening and baseline and weekly until week 6 of treatment ( or last visit ) . FRS for patients aged ≥30 years was calculated using an algorithm derived from the Framingham Heart Study . Baseline-to-endpoint least-squares mean changes in age-adjusted FRS by gender were compared using analysis of covariance ( baseline adjusted ) . RESULTS Men who received olanzapine demonstrated a mean increase in their total cholesterol levels ( + 18.5 mg/dL ; N = 53 ) and low-density lipoprotein cholesterol levels ( + 13.0 mg/dL ; N = 45 ) , whereas men who received ziprasidone demonstrated a mean decrease in their total cholesterol levels ( -8.5 mg/dL ; N = 44 ) and low-density lipoprotein cholesterol levels ( -7.2 mg/dL ; N = 40 ) ( p = .0006 and p = .004 , respectively ) . Additionally , men who received olanzapine showed an increase in baseline FRS ( + 7.69 % ; N = 53 ) , whereas men who received ziprasidone showed a decrease in baseline FRS ( -11.06 % ; N = 42 ) ( p = .09 ) . In women , treatment differences in FSR numerically favored ziprasidone but were not statistically significant . Neither treatment had a significant effect on blood pressure . CONCLUSION In short-term treatment , olanza-pine was associated with a significant worsening of lipid profile compared with ziprasidone , with a consequent increase in FRS versus ziprasidone . These findings , coupled with the significant weight gain in patients treated with olanzapine versus ziprasidone , warrant investigation in longer-term trials INTRODUCTION Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions . The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia . METHODS The study was an 8-week , double-blind , parallel-group , r and omized , controlled multicenter trial ( NCT00145444 ) . Seventy-six patients with schizophreniform disorder , schizophrenia or schizoaffective disorder ( diagnosis < 5 y ) , and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study . Efficacy of ziprasidone ( 80 - 160 mg/d ) and olanzapine 10 - 20 mg was measured using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression ( CGI ) Scale , the Calgary Depression Scale for Schizophrenia ( CDSS ) , and the Heinrich Quality of Life Scale ( HQLS ) ; tolerability assessment s included laboratory assessment s , body weight , and electroencephalogram . RESULTS Olanzapine ( n = 34 ) and ziprasidone ( n = 39 ) showed equal efficacy as measured by the PANSS , CDSS , CGI , and HQLS . However , mean weight gain was significantly higher in the olanzapine group ( 6.8 vs 0.1 kg , P < .001 ) . Ziprasidone was associated with decreasing levels of triglycerides , cholesterol , and transaminases , while these parameters increased in the olanzapine group ( all P values < .05 ) . There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects . Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently ( P < .05 ) . DISCUSSION The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile . However , there is a risk of a type II error with this sample size . Clinical ly significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine , while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms Objective : To examine the tolerability of the recommended initiation doses for once-monthly injectable paliperidone palmitate in patients who have recently been diagnosed with schizophrenia and for whom high doses may pose tolerability concerns . Methods : A post hoc analysis from a 13-week double-blind study of patients with schizophrenia r and omized 1:1:1:1 to placebo or paliperidone palmitate at 25 , 100 , or 150 mg equivalents ( mg eq ) of paliperidone ( corresponding to 39 , 156 , or 234 mg respectively ) . This analysis focused on the recently diagnosed subgroup ( ≤5 years ; N = 146 ) who received the recommended initiation dosage of paliperidone palmitate [ 150 mg eq on day 1 ( n = 109 ) followed by 100 mg eq on day 8 ( n = 39 ) ] or placebo ( n = 37 ) . Adverse events ( AEs ) , reported in ≥2 % of patients receiving paliperidone palmitate during days 1–7 or ≥5 % during days 8–36 , and in a higher percentage of patients receiving paliperidone palmitate than placebo , were identified . AE relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were determined . A RR was considered potentially significant when its 95 % CI did not include 1 . Results : Overall , day 1–7 AE rates were 37.6 % ( 41 of 109 ) and 29.7 % ( 11 of 37 ) with paliperidone palmitate and placebo respectively ; injection site pain ( 5.5 % versus 2.7 % , RR 2.0 ; 95 % CI 0.25 to 16.37 ) , agitation ( 4.6 % versus 2.7 % ; RR 1.7 ; 95 % CI 0.21 to 14.06 ) , and headache ( 3.7 % versus 0.0 % ; RR 3.1 ; 95 % CI 0.17 to 56.41 ) met the ≥2 % criteria . Day 8–36 AE rates were 41.0 % ( 16 of 39 ) and 37.8 % ( 14 of 37 ) with paliperidone palmitate and placebo respectively ; anxiety ( 5.1 % versus 0.0 % ; RR 4.8 ; 95 % CI 0.24 to 95.76 ) met the ≥5 % criteria . Key limitations were that some patients may have been ill for a significant time before formal diagnosis and that the number of patients is low in this subgroup , limiting the ability to detect statistical significance for AE RRs . Conclusions : Paliperidone palmitate initiation doses ( 150 mg eq day 1 , 100 mg eq day 8) were tolerated in this subgroup of patients who were recently diagnosed with schizophrenia , with no unexpected findings . Although the same size was small , these data identified AEs that may be encountered during the week and month after initiation dosing . These findings may assist clinicians when paliperidone palmitate is considered an appropriate treatment choice for these patients In this double-blind study , patients with an acute exacerbation of schizophrenia or schizoaffective disorder were r and omized to receive either ziprasidone 80 mg/day ( n = 106 ) or 160 mg/day ( n = 104 ) or placebo ( n = 92 ) , for 6 weeks . Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total , BPRS total , BPRS core items , CGI-S , and PANSS negative subscale scores ( p < .05 ) . Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinical ly significant depression at baseline ( MADRS ≥ 14 , over-all mean 23.5 ) ( p < .05 ) as compared with placebo . The percentage of patients experiencing adverse events was similar in each treatment group , and result ant discontinuation was rare . The most frequent adverse events associated with ziprasidone were generally mild dyspepsia , nausea , dizziness , and transient somnolence . Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain . The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive , negative , and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder OBJECTIVE This study was design ed to evaluate the short-term efficacy and safety of once-daily lurasidone ( 80 mg/day and 160 mg/day ) in the treatment of an acute exacerbation of schizophrenia . METHODS Participants , who were recently admitted in patients with schizophrenia with an acute exacerbation of psychotic symptoms , were r and omly assigned to 6 weeks of fixed-dose , double-blind treatment with lurasidone 80 mg ( n=125 ) , lurasidone 160 mg ( n=121 ) , quetiapine XR 600 mg ( QXR-600 mg ; n=119 ; active control included to test for assay sensitivity ) , or placebo ( n=121 ) , all dosed once daily in the evening . Efficacy was evaluated using a mixed-model repeated- measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( the primary efficacy measure ) and Clinical Global Impressions severity ( CGI-S ) score ( the key secondary efficacy measure ) . RESULTS Treatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score , PANSS positive and negative subscale scores , and CGI-S score compared with placebo . The endpoint responder rate ( ≥ 20 % improvement in PANSS total score ) was higher in subjects treated with lurasidone 80 mg ( 65 % ; p<0.001 ) , lurasidone 160 mg ( 79 % ; p<0.001 ) , and QXR-600 mg ( 79 % ; p<0.001 ) compared with placebo ( 41 % ) . The proportion of patients experiencing ≥ 7 % weight gain was 4 % for each lurasidone group , 15 % for the QXR-600 mg group , and 3 % for the placebo group . Endpoint changes in levels of cholesterol , triglycerides , and low-density lipoprotein ( LDL ) cholesterol were comparable for both lurasidone groups and placebo , while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol ( p<0.001 ) , LDL cholesterol ( p<0.01 ) , and triglycerides ( p<0.05 ) . CONCLUSIONS Lurasidone 80 mg and 160 mg doses administered once-daily in the evening , were safe and effective treatments for subjects with acute schizophrenia , with increased response rates observed at the higher dose . Dose-related adverse effects were limited , and both doses were generally well-tolerated OBJECTIVE This phase 3 study evaluated the efficacy , safety , and tolerability of cariprazine in patients with acute exacerbation of schizophrenia . METHOD This multinational , r and omized , double-blind , placebo- and active-controlled study was conducted from April 2010 to December 2011 . Patients who met DSM-IV-TR criteria for schizophrenia were r and omized to placebo ( n = 153 ) , cariprazine 3 mg/d ( n = 155 ) , cariprazine 6 mg/d ( n = 157 ) , or aripiprazole 10 mg/d ( n = 152 ) for 6 weeks of double-blind treatment . The primary and secondary efficacy parameters were mean change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score and Clinical Global Impressions-Severity of Illness ( CGI-S ) score , respectively . RESULTS Least squares mean differences ( LSMDs ) in PANSS total score change at week 6 significantly favored cariprazine 3 and 6 mg/d versus placebo ( LSMD [ 95 % CI ] : 3 mg/d , -6.0 [ -10.1 to -1.9 ] , adjusted P = .0044 ; 6 mg/d , -8.8 [ -12.9 to -4.7 ] , adjusted P < .0001 ) . Cariprazine 3 and 6 mg/d were also associated with significant improvements relative to placebo in CGI-S scores ( LSMD [ 95 % CI ] : 3 mg/d , -0.4 [ -0.6 to -0.2 ] , adjusted P = .0044 ; 6 mg/d , -0.5 [ -0.7 to -0.3 ] , adjusted P < .0001 ) . Significant differences from placebo were also observed with aripiprazole on the PANSS ( LSMD [ 95 % CI ] : -7.0 [ -11.0 to -2.9 ] , P = .0008 ) and CGI-S ( LSMD [ 95 % CI ] : -0.4 [ -0.6 to -0.2 ] , P = .0001 ) . Common treatment-emergent adverse events ( ≥ 10 % ) were insomnia ( all groups ) , akathisia ( cariprazine 6 mg/d ) , and headache ( placebo , cariprazine 6 mg/d ) . CONCLUSIONS This study supports the efficacy , safety , and tolerability of cariprazine 3 and 6 mg/d in the treatment of patients with acute exacerbation of schizophrenia . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01104766 Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable . We describe the first large-scale double-masked r and omized comparison with first-episode patients of aripiprazole and risperidone , 2 commonly used first-episode treatment agents . One hundred ninety-eight participants aged 15 - 40 years with schizophrenia , schizophreniform disorder , schizoaffective disorder or psychotic disorder Not Otherwise Specified , and who had been treated in their lifetime with antipsychotics for 2 weeks or less were r and omly assigned to double-masked aripiprazole ( 5 - 30 mg/d ) or risperidone ( 1 - 6 mg/d ) and followed for 12 weeks . Positive symptom response rates did not differ ( 62.8 % vs 56.8 % ) nor did time to response . Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia . Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol , fasting glucose , and prolactin levels . Post hoc analyses suggested advantages for aripiprazole on depressed mood . Overall , if the potential for akathisia is a concern , low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole . Otherwise , aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications INTRODUCTION Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania . This study ( NCT00694707 ) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia . METHODS This study was a multinational , double-blind , r and omized , placebo- and active-controlled , fixed-dose trial . Patients were r and omized to receive placebo , cariprazine 1.5mg/d , cariprazine 3.0mg/d , cariprazine 4.5mg/d , or risperidone 4.0mg/d ( for assay sensitivity ) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up . Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale ( PANSS ) total and Global Impressions-Severity of Illness ( CGI-S ) scores , respectively . Safety parameters included adverse events ( AEs ) , vital signs , laboratory measures , and extrapyramidal symptom ( EPS ) scales . RESULTS Of 732 r and omized patients , 64 % completed the study . PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5mg/d , 3.0mg/d , and 4.5mg/d ( least squares mean difference [ LSMD ] : -7.6 , -8.8 , -10.4 , respectively ; p<0.001 ; LOCF ) and risperidone ( -15.1 , p<0.001 ; LOCF ) ; significant improvement on CGI-S was demonstrated for all active treatments ( p<0.05 ) . The most frequent cariprazine AEs ( ≥ 5 % and at least twice the rate of the placebo group ) were insomnia , extrapyramidal disorder , akathisia , sedation , nausea , dizziness , and constipation . Mean changes in metabolic parameters were small and similar between groups . CONCLUSION The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia UNLABELLED Vabicaserin , a potent 5-HT2C receptor agonist , decreases nucleus accumbens extracellular dopamine levels in rats , without affecting striatal dopamine , indicating mesolimbic selectivity . This is the first study of efficacy , safety and tolerability of vabicaserin in adults with acute schizophrenia . Three hundred fourteen hospitalized subjects were r and omized to : Vabicaserin 200 or 400 mg/day , olanzapine 15 mg/day or placebo . Central raters assessed the PANSS and CGI-S. Site raters performed the BPRS and CGI-I. Central rated PANSS Positive ( PANSS-PPS ) was the primary endpoint . Two hundred eighty-nine subjects were included in the mITT efficacy analysis . Vabicaserin was well tolerated with no major safety concerns . Olanzapine , but not vabicaserin , caused weight gain . Vabicaserin 200 mg/day and olanzapine demonstrated significant improvement at week 6 vs. placebo on PANSS-PSS . A non-significant decrease vs. placebo was observed for 400 mg/day . Both vabicaserin groups demonstrated significant improvement over baseline on PANSS Negative while placebo worsened . Vabicaserin 200 mg/day and olanzapine demonstrated significantly greater improvement over placebo on PANSS Total whereas 400 mg/day showed a trend toward improvement . There was no significant improvement vs. placebo for either vabicaserin group on site-rated BPRS . Vabicaserin 200 mg/day and olanzapine demonstrated significant improvement vs. placebo on CGI-I and CGI-S but not 400 mg/day vabicaserin . Vabicaserin demonstrated efficacy on primary and secondary endpoints at 200 mg/day , but not at 400 mg/day which showed a trend for efficacy . The 200 mg/day vabicaserin group achieved proof of concept using central ratings . Both vabicaserin doses were well tolerated with no significant safety signals and no weight gain . TRIAL REGISTRATION clinical trials.gov . Identifier : NCT00265551 The study objectives were to evaluate the efficacy , safety , tolerability , and pharmacokinetics of RP5063 versus placebo . The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder . This 28-day , multicenter , placebo-controlled , double-blind study r and omized 234 subjects to RP5063 15 , 30 , or 50 mg ; aripiprazole ; or placebo ( 3:3:3:1:2 ) once daily . The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy . The primary endpoint was change from baseline to Day 28/EOT ( End-of-Treatment ) in Positive and Negative Syndrome Scale ( PANSS ) total score ; secondary endpoints included PANSS subscales , improvement ≥1 point on the Clinical Global Impressions-Severity ( CGI-S ) , depression and cognition scales . The primary analysis of PANSS Total showed improvement by a mean ( SE ) of -20.23 ( 2.65 ) , -15.42 ( 2.04 ) , and -19.21 ( 2.39 ) in the RP5063 15 , 30 , and 50 mg arms , versus -11.41 ( 3.45 ) in the placebo arm . The difference between treatment and placebo reached statistical significance for the 15 mg ( p=0.021 ) and 50 mg ( p=0.016 ) arms . Improvement with RP5063 was also seen for multiple secondary efficacy outcomes . Discontinuation for any reason was much lower for RP5063 ( 14 % , 25 % , 12 % ) versus placebo ( 26 % ) and aripiprazole ( 35 % ) . The most common treatment-emergent adverse events ( TEAE ) in the RP5063 groups were insomnia and agitation . There were no significant changes in body weight , electrocardiogram , or incidence of orthostatic hypotension ; there was a decrease in blood glucose , lipid profiles , and prolactin levels . In conclusion , the novel dopamine serotonin stabilizer , RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder Abstract Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia , but many adverse effects are noted . Clinicians usually hesitate to switch from clozapine to other antipsychotics because of the risk of a re-emergence or worsening of the psychosis , although empirical studies are very limited . Zotepine , an atypical antipsychotic with a pharmacologic profile similar to clozapine , was found to be an effective treatment for patients with treatment-resistant schizophrenia in Japan . This 12-week study is the first prospect i ve , r and omized , and rater-blind study to investigate the efficacy and tolerability of switching from clozapine to zotepine . Fifty-nine patients with schizophrenia , who had taken clozapine for at least 6 months with a Clinical Global Impression – Severity score of at least 3 , were r and omly allocated to the zotepine and the clozapine groups . At the end of the study , 52 patients ( 88 % ) had completed the trial . The 7 withdrawal cases were all in the zotepine group . The final mean ( SD ) dose of zotepine and clozapine was 397.1 ( 75.7 ) versus 377.1 ( 62.5 ) mg/d , respectively . Patients in the zotepine group showed a significant increase in the Brief Psychiatric Rating Scale [ mean ( SD ) , 4.7 ( 8.7 ) vs −1.3 ( 6.3 ) ; P = 0.005 ] , more general adverse effects as revealed by the Udvalg for Kliniske Undersogelser Rating Scale [ mean ( SD ) , 1.74 ( 3.9 ) vs −0.2 ( 2.8 ) ; P = 0.039 ] , more extrapyramidal adverse effects as demonstrated by the Simpson and Angus Scale [ mean ( SD ) , 1.29 ( 3.5 ) vs 0.17 ( 2.1 ) ; P = 0.022 ] , an increased use of propranolol ( 37.1 % vs 0 % , P < 0.0001 ) and anticholinergics ( 25.7 % vs 0 % , P = 0.008 ) , and an increased level of prolactin ( 29.6 vs −3.8 ng/ mL , P < 0.0005 ) , compared with the clozapine group . The results suggested that switching from clozapine to zotepine treatment should be done with caution OBJECTIVE --To assess the validity of the 1990 US weight guidelines for women that support a substantial gain in weight at approximately 35 years of age and recommend a range of body mass index ( BMI ) ( defined as weight in kilograms divided by the square of height in meters ) from 21 to 27 kg/m2 , in terms of coronary heart disease ( CHD ) risk in women . DESIGN -- Prospect i ve cohort study . SETTING --Female registered nurses in the United States . PARTICIPANTS --A total of 115,818 women aged 30 to 55 years in 1976 and without a history of previous CHD . MAIN OUTCOME MEASURE -- Incidence of CHD defined as nonfatal myocardial infa rct ion or fatal CHD . RESULTS --During 14 years of follow-up , 1292 cases of CHD were ascertained . After controlling for age , smoking , menopausal status , postmenopausal hormone use , and parental history of CHD and using as a reference women with a BMI of less than 21 kg/m2 , relative risks ( RRs ) and 95 % confidence intervals ( CIs ) for CHD were 1.19 ( 0.97 to 1.44 ) for a BMI of 21 to 22.9 kg/m2 , 1.46 ( 1.20 to 1.77 ) for a BMI of 23 to 24.9 kg/m2 , 2.06 ( 1.72 to 2.48 ) for a BMI of 25 to 28.9 kg/m2 , and 3.56 ( 2.96 to 4.29 ) for a BMI of 29 kg/m2 or more . Women who gained weight from 18 years of age were compared with those with stable weight ( + /- 5 kg ) in analyses that controlled for the same variables as well as BMI at 18 years of age . The RRs and CIs were 1.25 ( 1.01 to 1.55 ) for a 5- to 7.9-kg gain , 1.64 ( 1.33 to 2.04 ) for an 8- to 10.9-kg gain , 1.92 ( 1.61 to 2.29 ) for an 11- to 19-kg gain , and 2.65 ( 2.17 to 3.22 ) for a gain of 20 kg or more . Among women with the BMI range of 18 to 25 kg/m2 , weight gain after 18 years of age remained a strong predictor of CHD risk . CONCLUSIONS --Higher levels of body weight within the " normal " range , as well as modest weight gains after 18 years of age , appear to increase risks of CHD in middle-aged women . These data provide evidence that current US weight guidelines may be falsely reassuring to the large proportion of women older than 35 years who are within the current guidelines but have potentially avoidable risks of CHD INTRODUCTION Activation of metabotropic glutamate ( mGluR2/3 ) receptors has been proposed as an alternative mechanism to dopaminergic-based antipsychotics to correct glutamatergic deficits hypothesized to underlie schizophrenia symptoms . This study investigates the efficacy and safety of AZD8529 , a selective positive allosteric modulator ( PAM ) at the mGlu2 receptor , in symptomatic patients with schizophrenia . METHODS Patients were r and omized to receive AZD8529 40 mg , risperidone 4 mg , or placebo as monotherapy . Treatment lasted for 28 days , and clinical efficacy was assessed using Positive and Negative Syndrome Scale ( PANSS ) and Clinical Global Impression ( CGI ) scores . RESULTS There were no significant differences between patients treated with AZD8529 versus placebo in change from baseline to endpoint in PANSS total , negative and positive symptom subscale , or CGI-S scores . In contrast , risperidone demonstrated significant efficacy relative to placebo . CONCLUSION These results do not support a role for the mGluR-2 PAM AZD8529 as an antipsychotic and indicate that positive modulation of mGluR type 2 receptors alone is not sufficient for antipsychotic effects in acutely ill schizophrenia patients OBJECTIVE This study compares the efficacy of risperidone and olanzapine to that of first-generation antipsychotics ( FGAs ) in patients with schizophrenia , who failed to show a response to initial trials of FGAs . METHOD This study was an 8-week treatment , r and omized , rater-blind , active-control study with 3 treatment arms . 48 patients , who showed inadequate response to 1 FGA , were enrolled and r and omized into risperidone , olanzapine , or FGA ( haloperidol or trifluoperazine ) groups . They were blindly assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression Scale-Severity , and the Extrapyramidal Symptom Rating Scale ( ESRS ) at baseline and biweekly . RESULTS All 3 groups demonstrated a significant decrease in the PANSS total , positive , and general scores from baseline to endpoint ( p-values range from 0.003 to 0.021 ) . There were no significant differences among the 3 groups in score changes . The olanzapine group had significant score reductions than the risperidone and FGAs groups in terms of the ESRS subjective total score and did not experience a significant increase in the dose of anticholinergics . The FGA group demonstrated that extrapyramidal syndrome ( EPS ) worsened under an increased dosage of anti-EPS drugs . Olanzapine was associated with significant body weight gain ( 2.69 ± 4.0 kg , p=0.026 ) , but there were no significant group differences on weight gain . CONCLUSIONS Haloperidol or trifluoperazine demonstrated similar efficacy as risperidone or olanzapine for patients with schizophrenia who had failed their first trial with a FGA . Related double-blind , fixed dose studies with a larger sample size are needed to confirm the results of our study Abstract The benzamide amisulpride ( ASP ) is a selective D2-like dopamine antagonist , while flupentixol ( FPX ) , a thioxanthene , blocks D2-like , D1-like and 5-HT2 receptors . To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability , a r and omized double-blind multi-center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia ( DSM-III-R ) with predominant positive symptomatology . Doses were initially fixed ( ASP : 1000 mg/day ; FPX : 25 mg/day ) but could be reduced by 40 % in case of side effects ( mean daily doses : ASP : 956 mg ; FPX : 22.6 mg ) . Intention-to-treat evaluation demonstrated significant improvement under both medications . The difference between the mean BPRS decreases of both treatment groups was 5.6 points ( 95 % CI : 0.55 ; 10.65 ) in favour of ASP . According to CGI , 62 % of patients in either drug group were treatment responders . ANCOVA analysis showed that reductions of BPRS ( ASP : −42 % ; FPX : −32 % ) and SAPS ( ASP : −78 % ; FPX : −65 % ) were more pronounced under ASP . Due to adverse events , significantly fewer ASP patients ( 6 % ) were withdrawn from the study ( FPX : 18 % ) . Extrapyramidal tolerability was better in the ASP group , as demonstrated by smaller increases in the Simpson-Angus Scale , the AIMS , and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate . ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology , while extrapyramidal tolerability is better . These conclusions have to be drawn cautiously , as dosage effects on outcome parameters can not be entirely ruled out . The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability OBJECTIVE This study compared the effects of atypical antipsychotics ( risperidone or quetiapine ) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization . METHODS This international , r and omized , double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase . Recently exacerbated patients with schizophrenia or schizoaffective disorder ( DSM-IV ) were r and omized ( 2:2:1 ) to risperidone ( n = 153 ) , quetiapine ( n = 156 ) , or placebo ( n = 73 ) . Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5 , with the ability to increase to 600 or 800 mg/day of quetiapine on day 8 . The main outcome measures were the total Positive and Negative Syndrome Scale ( PANSS ) and need for additional psychotropic medications . RESULTS Monotherapy Phase : The combined atypical antipsychotic group ( n = 308 ) reached borderline superiority to placebo ( n = 71 ) at the 2-week endpoint on mean change in total PANSS score ( -24.1 + /- 1.2 and -20.2 + /- 2.0 , respectively ; p = 0.067 ) . The change in the atypical group was driven by the improvement with risperidone ( -27.7 + /- 1.5 vs. -20.2 + /- 2.0 with placebo , p < 0.01 ; and vs. -20.5 + /- 1.5 with quetiapine , p < 0.01 ) ; the improvement with quetiapine was similar to placebo , p = 0.879 . Results were similar on other efficacy endpoints . Additive Therapy Phase : Additional psychotropics were prescribed to fewer ( p < 0.01 ) risperidone ( 36 % ) than quetiapine ( 53 % ) or placebo patients ( 59 % ) . The overall discontinuation rate was 18 % , 26 % , and 38 % , respectively . Risperidone , compared with placebo , was associated with more parkinsonism , akathisia , plasma prolactin changes , and weight gain ; while quetiapine was associated with more somnolence , sedation , dizziness , constipation , tachycardia , thyroid dysregulation , and weight gain . CONCLUSION While the combined atypical antipsychotic group did not experience greater improvements than the placebo group , risperidone , but not quetiapine , was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder , with no unexpected tolerability findings Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions . There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds . But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics . This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia . Patients were r and omized to receive quetiapine or olanzapine for 8 weeks . Cognitive function was assessed at baseline , week 4 and week 8 . Efficacy was assessed weekly using the Positive and Negative Syndrome Scale ( PANSS ) and the Clinical Global Improvement Scale ( CGI ) . Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale ( ESRS ) , the Barnes Akathisia Scale ( BAS ) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale ( UKU ) . In total , 52 patients were enrolled in the study . Data from the 33 patients who completed cognitive assessment s at two or more time points out of three ( baseline , Week 4 and Week 8) are analyzed here . Both quetiapine and olanzapine improved global cognitive index z-scores , however , this was more marked with quetiapine . Between-group comparisons showed significantly greater improvements in reaction quality /attention with quetiapine than olanzapine . Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores . Both treatments were well tolerated , especially no EPS occurred during 8 weeks of treatment . Both quetiapine and olanzapine improved cognition ; however , the improvement in cognitive index scores was more marked in patients receiving quetiapine . Furthermore , quetiapine produced a significantly greater improvement in reaction quality /attention than olanzapine PURPOSE To compare the efficacy and safety of amisulpride and olanzapine in subjects with schizophrenia and comorbid depression in a r and omised double-blind trial . PATIENTS Eighty-five adult patients fulfilling DSM-IV criteria for schizophrenia and presenting a depressive episode were r and omised to amisulpride ( 200 - 600 mg/day ) or olanzapine ( 5 - 15 mg/day ) for 8 weeks . Primary efficacy variables were change in Calgary Depression Scale ( CDS ) score and Clinical Global Impression ( CGI ) of Change . Safety was monitored by adverse event reporting and determination of extrapyramidal function and metabolic variables . RESULTS The mean change from baseline of CDS score was -6.84 in the amisulpride group and -7.36 in the olanzapine group . 65.9 % and 61.5 % of subjects , respectively , were considered " much " or " very much " improved . No significant inter-group difference in effect size was observed . The frequency of adverse events was low and emergence of extrapyramidal symptoms was not seen . Four patients in the olanzapine group developed abnormal triglyceride levels . Mean weight gain was 1.45 and 0.5 kg , respectively , in the olanzapine and amisulpride groups . CONCLUSION Amisulpride and olanzapine are effective in patients with schizophrenia and comorbid depression . Tolerance of both drugs was acceptable , although use of olanzapine was associated with a trend toward greater metabolic side-effects This 6-week , double-blind , placebo-controlled study evaluated paliperidone extended-release ( ER ) as both monotherapy and adjunctive therapy to mood stabilizers and /or antidepressants ( MS/ADs ) for schizoaffective disorder . Included subjects had a schizoaffective disorder diagnosis ; a Positive and Negative Syndrome Scale ( PANSS ) total score of 60 or higher ; a score of 4 or higher on 2 or more of the PANSS items for hostility , excitement , tension , uncooperativeness , or poor impulse control ; and prominent mood symptoms ( ≥16 on the Young Mania Rating Scale and /or the 21-item Hamilton Rating Scale for Depression ) . Subjects were r and omized to 6 mg/d paliperidone ER or placebo with flexible dosing ( 3 - 12 mg/d ) until day 15 . R and omization was stratified by use of MS/AD and study site . The primary analysis outcome was change in PANSS total score at week 6 last observation carried forward end point . A total of 311 subjects received paliperidone ER ( n = 216 ) or placebo ( n = 95 ) ; 52.0 % received MS/AD . The mean ( SD ) modal dose of paliperidone ER was 8.6 ( 2.5 ) mg/d . Greater improvement was observed with paliperidone ER than placebo on mean ( SE ) PANSS total scores : −20.0 ( 1.3 ) and −10.8 ( 1.9 ) , respectively . Subjects with prominent manic or depressive symptoms showed greater improvement with paliperidone ER versus placebo : mean ( SE ) Young Mania Rating Scale ( −10.6 [ 0.9 ] vs −5.7 [ 1.2 ] , respectively ) and 21-item Hamilton Rating Scale for Depression ( −10.2 [ 0.7 ] vs −6.2 [ 1.1 ] , respectively ) . The most common adverse events with paliperidone ER were headache , akathisia , dizziness , insomnia , and dyspepsia . Paliperidone ER improved psychotic and affective symptoms both as monotherapy and as an adjunct to MS/AD . No new safety findings were observed in this population AIM This study aim ed to evaluate the efficacy , safety , and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia ( SCZ ) . METHODS We conducted a 6-week , multicenter , double-blind , placebo-controlled , phase 2/3 study in Japan . Patients with acute SCZ were r and omized ( 1:1:1:1 ) to receive brexpiprazole 1 mg , 2 mg , 4 mg , or placebo once a day . The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total scores . RESULTS In the 459 patients that were r and omized , brexpiprazole 2 mg showed a significant improvement versus placebo ( treatment difference : -7.32 , P = 0.0124 ) , although brexpiprazole 4 mg showed numerical improvements ( treatment difference : -3.86 , P = 0.1959 ) , and brexpiprazole 1 mg showed only minimal change ( treatment difference : -0.63 , P = 0.8330 ) . Treatment-emergent adverse events with an incidence of ≥5 % and ≥2 times the rate of placebo in the brexpiprazole groups were vomiting , elevated blood prolactin , diarrhea , nausea , and dental caries . Most treatment-emergent adverse events were mild or moderate in severity . There were no clinical ly significant changes in electrocardiogram parameters , bodyweight , laboratory values , or vital signs in the brexpiprazole groups . CONCLUSION Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute SCZ OBJECTIVE To evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) in a 6-week , double-blind , r and omized study . METHOD Patients with a DSM-IV diagnosis of acute schizophrenia were r and omly assigned to fixed-dose quetiapine XR 400 , 600 , or 800 mg/day ( once daily in the evening ) , quetiapine immediate release ( IR ) 400 mg/day ( 200 mg twice daily ) , or placebo . Dual-matched placebo was used to maintain blinding . Quetiapine XR target doses were reached by day 2 ( 400 and 600 mg ) and day 3 ( 800 mg ) . The primary endpoint was least squares mean change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score . PANSS response rate ( percentage of patients with > or = 30 % reduction in total score ) , Clinical Global Impressions-Improvement scale ( CGI-I ) response rate ( percentage of patients with score < or = 3 ) , change in CGI-Severity of Illness ( CGI-S ) , and adverse events ( AEs ) were also assessed . The study was conducted from November 2004 to December 2005 . RESULTS 588 patients were enrolled and 446 ( 76 % ) completed the study . Improvement in PANSS total score at week 6 was significant versus placebo ( -18.8 ) in all groups : -24.8 ( p = .03 ) , -30.9 ( p < .001 ) , and -31.3 ( p < .001 ) for quetiapine XR 400 , 600 , and 800 mg , respectively , and -26.6 ( p = .004 ) for quetiapine IR . There were also statistically significant differences in PANSS and CGI-I response rates for all active treatments versus placebo ( all p < .05 ) . The most common AEs in all quetiapine groups were somnolence and dizziness ; there were no unexpected AEs with quetiapine XR . Incidence of AEs potentially related to extrapyramidal symptoms was similar to placebo . CONCLUSION Once-daily quetiapine XR ( 400 - 800 mg/day ) was effective versus placebo in patients with acute schizophrenia . Treatment , including rapid dose escalation , was well tolerated , with a therapeutically effective dose reached by day 2 . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00206115 OBJECTIVE This prospect i ve study examines the effect of clozapine on glucose control and insulin sensitivity . METHOD Glucose homeostasis was measured in nine female and 11 male patients with schizophrenia ( mean age=30.5 years , SD=7.4 ) before clozapine treatment and after a mean of 2.5 months ( SD=0.95 ) of clozapine treatment . Oral glucose tolerance and insulin levels were measured . Insulin resistance level was measured by the homeostasis model assessment . RESULTS Eleven ( 55 % ) of the patients developed abnormal glucose control ; the mean age of these patients was 30.2 ( SD=7.1 ) , and five were women . Patients ' insulin resistance at baseline ( mean insulin resistance level=3.88 , SD=2.93 ) was unaffected by clozapine . Mean fasting and 2-hour glucose levels significantly increased by 0.55 mmol/liter and 1.4 mmol/liter , respectively . There was no correlation between change in body mass index and change in fasting glucose levels . CONCLUSIONS Clozapine impairs glucose control within 4 months of treatment , independent of changes in insulin sensitivity and body mass index BACKGROUND AND PURPOSE Zotepine is cl aim ed to be a neuroleptic drug with atypical features . However , there have been few double-blind studies in Asian patients . The purpose of this study was to compare the efficacy and safety of zotepine and haloperidol in Taiwanese patients with schizophrenia . PATIENTS AND METHODS Patients with positive symptoms ( n = 70 ) were enrolled into this double-blind , r and omized study . Each patient received either zotepine 150 mg/day or haloperidol 9 mg/day . The Positive and Negative Syndrome Scale ( PANSS ) , Brief Psychiatric Rating Scale ( BPRS ) , and Clinical Global Impression ( CGI ) were assessed on Days 0 , 3 , 7 , 14 , 28 , and 42 after the start of treatment . Adverse events were recorded during the trial period . The analyses were carried out on an intent-to-treat basis with the last observation carried forward . RESULTS In terms of the score reduction in the PANSS , BPRS , and CGI , all analyses indicated that there were no significant differences between the groups at the end of the trial . Patients who received zotepine had no acute dystonia and less severe parkinsonism ( p < 0.05 or 0.10 ) , but significantly more dizziness , body weight gain , and pulse rate increase . CONCLUSION In this 6-week trial , zotepine at 150 mg/day was as efficacious as haloperidol 9 mg/day in the treatment of Taiwanese patients with schizophrenia . Zotepine treatment produced fewer extrapyramidal symptoms but had a greater frequency of sedative effects compared to haloperidol OBJECTIVE Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder . This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large , controlled clinical trial . METHOD Patients with first-episode psychosis ( N=263 ) were r and omly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks . Domains measured included psychopathology , psychosocial variables , neurocognitive functioning , and brain morphology and metabolism . This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase . RESULTS Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity , which did not differ significantly in last-observation-carried-forward analyses . However , in a mixed-model analysis , olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating . Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain , compared with the haloperidol-treated patients . Overall , significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study ( 67 % versus 54 % ) . CONCLUSIONS As expected on the basis of previous studies , both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis . However , olanzapine had several relative advantages in therapeutic response . Although the nature of adverse events differed between the two agents , retention in the study was greater with olanzapine . Retention in treatment is important in this patient population , given their risk of relapse . Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia Olanzapine is a potential new “ atypical ” antipsychotic agent . This double-blind , acute phase study compared two doses of olanzapine [ 1 mg/day ( Olz1.0 ) ; 10 mg/day ( Olz10.0 ) ] with placebo in the treatment of 152 patients who met the DSM-III-R criteria for schizophrenia and had a Brief Psychiatric Rating Scale (BPRS)-total score ( items scored 0–6 ) ≥24 . In overall symptomatology improvement [ BPRS-total score and Positive and Negative Syndrome Scale (PANSS)-total score ] , Olz10.0 was statistically significantly superior to placebo . In positive symptom improvement ( PANSS-positive score , BPRS-positive score ) , Olz10.0 was statistically significantly superior to placebo . In negative symptom improvement ( PANSS-negative score ) , Olz10.0 was statistically superior to placebo . Olz 1.0 was clinical ly comparable to placebo in all efficacy comparisons . The only adverse event to show an overall statistically significant incidence difference was anorexia ( reported for 10 % of placebo-treated and 0 % of Olz10.0-treated patients ) . The Olz10.0-treated patients improved over baseline with respect to parkinsonian and akathisia symptoms , and these changes were comparable with those observed with placebo . There were no dystonias associated with Olz10.0 treatment . At endpoint , the incidence of patients with elevated prolactin values did not differ statistically significantly between placebo-treated and Olz10.0-treated patients . Olanzapine appears to be not only safe and effective , but a promising atypical antipsychotic c and i date BACKGROUND Lurasidone is a new atypical antipsychotic agent with high affinity for D(2 ) , 5-HT(2A ) and 5-HT(7 ) receptors . The current study evaluated the safety and efficacy of lurasidone and ziprasidone in stable out patients diagnosed with schizophrenia or schizoaffective disorder . METHODS Adult out patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder that was chronic ( ≥6 months duration ) and stable were r and omized to 21 days of double-blind treatment with a fixed dose of lurasidone 120 mg once daily ( N=150 ) or ziprasidone 80 mg BID ( N=151 ) . Changes from baseline in efficacy measures were evaluated using mixed model for repeated measures ( MMRM ) analyses . RESULTS The proportion of patients who discontinued from the study was similar for lurasidone and ziprasidone ( 32.5 % vs. 30.7 % ) ; the proportion who discontinued due to adverse events was similar ( 10.4 % vs. 11.1 % ) . Treatment with lurasidone and ziprasidone was associated with a small endpoint reduction in median weight ( -0.65 kg vs. -0.35 kg ) and median total cholesterol ( -6.4 vs. -4.4 mg/dL ) ; no endpoint change was observed in median triglycerides ( 0.0 vs. 0.0 mg/dL ) . There were no clinical ly significant changes in other laboratory or ECG parameters . Improvement was observed on an MMRM analysis of the PANSS total score for lurasidone and ziprasidone at Week 1 ( -4.1 vs. -1.6 ; P=0.020 ) , Week 2 , ( -6.1 vs. -3.6 ; P=0.074 ) , and Week 3 ( -6.3 vs. -4.5 ; P=0.229 ) . CONCLUSION In this double-blind , fixed-dose comparison of lurasidone 120 mg and ziprasidone 160 mg , treatment with lurasidone was well-tolerated and safe , and was not associated with clinical ly significant changes from baseline in weight , metabolic parameters , or QTc interval . Study limitations include the relatively short trial duration and lack of placebo control OBJECTIVE The study was design ed to evaluate the short-term efficacy and safety of lurasidone in the treatment of acute schizophrenia . METHOD Participants , who were recently admitted in patients with schizophrenia with an acute exacerbation of psychotic symptoms , were r and omly assigned to 6 weeks of double-blind treatment with 40 mg of lurasidone , 120 mg of lurasidone , 15 mg of olanzapine ( included to test for assay sensitivity ) , or placebo , dosed once daily . Efficacy was evaluated using a mixed-model repeated- measures analysis of the change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( as the primary efficacy measure ) and Clinical Global Impressions severity ( CGI-S ) score ( as the key secondary efficacy measure ) . RESULTS Treatment with both doses of lurasidone or with olanzapine was associated with significantly greater improvement at week 6 on PANSS total score , PANSS positive and negative subscale scores , and CGI-S score compared with placebo . There was no statistically significant difference in mean PANSS total or CGI-S change scores for the lurasidone groups compared with the olanzapine group . With responders defined as those with an improvement of at least 20 % on the PANSS , endpoint responder rates were significant compared with placebo for olanzapine only . The incidence of akathisia was higher with 120 mg of lurasidone ( 22.9 % ) than with 40 mg of lurasidone ( 11.8 % ) , olanzapine ( 7.4 % ) , or placebo ( 0.9 % ) . The proportion of patients experiencing ≥ 7 % weight gain was 5.9 % for the lurasidone groups combined , 34.4 % for the olanzapine group , and 7.0 % for the placebo group . CONCLUSIONS Lurasidone was an effective treatment for patients with acute schizophrenia . Safety assessment s indicated a higher frequency of adverse events associated with 120 mg/day of lurasidone compared with 40 mg/day OBJECTIVE This study was design ed to assess efficacy and safety of paliperidone extended-release ( ER ) in patients with schizoaffective disorder . METHOD A r and omized , 6-week , double-blind , placebo-controlled study was conducted . Subjects with a Structured Clinical Interview for DSM-IV diagnosis of schizoaffective disorder , Positive and Negative Syndrome Scale ( PANSS ) total score > or= 60 , score > or= 4 on > or= 2 PANSS items ( hostility , excitement , tension , uncooperativeness , poor impulse control ) , and Young Mania Rating Scale and /or Hamilton Depression Rating Scale , 21-item version scores > or= 16 were eligible . Subjects received higher-dose ( 12 mg/d ) or lower-dose ( 6 mg/d ) paliperidone ER . Dose adjustments by 3-mg increments were allowed until day 15 . The study was conducted from October 2006 through February 2008 . RESULTS A total of 316 subjects were r and omly assigned to paliperidone ER lower dose ( n = 109 ) , higher dose ( n = 100 ) , or placebo ( n = 107 ) . Mean + /- SD modal dose in lower- and higher-dose groups : 5.7 + /- 0.9 and 11.6 + /- 1.0 mg/d , respectively . Mean + /- SE PANSS total score ( primary outcome ) improved significantly with higher-dose paliperidone ER versus placebo ( -32.4 + /- 2.1 versus -24.1 + /- 2.1 ; P = .003 ) . Change with lower-dose paliperidone ER ( -27.7 + /- 2.1 ) was not significantly different from placebo ( P = .187 ) . No new safety issues were identified ; common adverse events were headache ( placebo : 16.8 % ; paliperidone ER : lower dose , 13.9 % , higher dose , 13.3 % ) and tremor ( 3.7 % , 12.0 % , 11.2 % , respectively ) . Mean prolactin and weight changes were greater with active treatment than placebo . CONCLUSIONS Higher-dose paliperidone ER was effective and well tolerated in patients with acute schizoaffective disorder . These findings and those from a companion study constitute the first registration program for antipsychotic treatment in schizoaffective disorder . TRIAL REGISTRATION clincaltrials.gov Identifier : NCT00397033 We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate ( PP ) in the treatment of schizophrenia . Patients were r and omized to receive gluteal injections of placebo or PP ( 50 or 100 mg eq. , fixed doses ) , without oral supplementation , on days 1 , 8 , and 36 ( 9-wk , double-blind phase ) in this phase 2b study . Patients ( n=197 , intent-to-treat analysis set ) were 62 % men , mean ( s.d . ) age 39 ( 10 ) yr , with a baseline mean ( s.d . ) Positive and Negative Syndrome Scale ( PANSS ) total score of 87.0 ( 12.5 ) . Mean ( s.d . ) PANSS total scores showed significant improvement at endpoint ( primary measure ) for both the PP 50 mg eq. [ -5.2 ( 21.5 ) ] and PP 100 mg eq. [ -7.8 ( 19.4 ) ] groups , vs. placebo [ 6.2 ( 18.3 ) ] ( p0.001 , each dose vs. placebo ) . This improvement was detected by day 8 and maintained to endpoint ( p0.011 ) for both doses . In the safety analysis set ( n=247 ) , fewer PP-treated patients ( 2 % ) discontinued for treatment-emergent adverse events vs. placebo-treated ( 10 % ) . Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo , with the exception of parkinsonism-related disorders ( 50 mg eq. 5 % , 100 mg eq. 8 % , placebo 1 % ) . Results of other safety measures suggest PP to be generally well-tolerated . Throughout the study , investigators rated injection-site pain as absent ( 56 - 71 % ) , mild ( 24 - 39 % ) , moderate ( 2 - 12 % ) , or severe ( 0 - 2 % ) . PP ( 50 and 100 mg eq. doses ) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia Summary Objective : To compare the efficacy and safety of the atypical antipsychotics amisulpride and olanzapine in the treatment of acute psychotic exacerbations of schizophrenia . Design and setting : A multinational , double-blind r and omised clinical trial . Patients and treatment : Three hundred and seventy-seven patients with predominantly positive symptomatology were treated for six months with either amisulpride ( 200 - 800 mg/d ) or olanzapine ( 5 - 20 mg/d ) . Main outcome measures : Short-term results were analysed after two months of treatment . The primary efficacy measure was the change of score on the Brief Psychiatric Rating Scale ( BPRS ) . Other measures of efficacy and safety were also evaluated . Results : Psychotic symptoms , as measured on the BPRS score , improved with both treatments , amisulpride being equivalent to olanzapine . All BPRS factor scores , as well as depressive symptoms , improved to a similar extent with both treatments . Less than five per cent of patients withdrew for adverse events , and there was no evidence for the emergence of extrapyramidal symptoms with either treatment . Statistically significant greater weight gain ( 2.7 ± 3.9 kg ) was observed during the study in the olanzapine group , compared with the amisulpride group ( 0.9 ± 3.2 kg , p < 0.0001 ) . Conclusions : Amisulpride and olanzapine show equivalent efficacy at 2 months in the treatment of acute psychotic exacerbations of schizophrenia . Amisulpride offers a significant advantage in preserving body weight OBJECTIVE Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality , leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids , including use of antipsychotic agents with low metabolic risk . This multicenter , r and omized , double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment . METHOD In total , 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were r and omly assigned to receive aripiprazole ( N = 88 ) or olanzapine ( N = 85 ) for 16 weeks in a study conducted from March 30 , 2004 , to August 8 , 2006 . Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels , respectively . RESULTS At week 16 , weight decreased significantly with aripiprazole versus olanzapine ( -1.8 vs. + 1.41 kg ; p < .001 ) . Significant differences in percentage change in triglyceride levels were observed with aripiprazole ( decreases ) versus olanzapine ( increases ) at all time-points . In addition , significantly more subjects receiving aripiprazole had clinical ly relevant ( > or = 7 % ) weight loss versus olanzapine ( 11.1 % vs. 2.6 % ; p = .038 ) , and a lower percentage of subjects receiving aripiprazole had clinical ly relevant weight gain ( 2.5 % vs. 9.1 % ; p = .082 ) . Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine , with no significant effects on glycemic laboratory measures . Mean Clinical Global Impressions-Improvement ( CGI-I ) scores for both groups were in the range of " no change " to " minimal improvement . " CGI-I endpoint scores were statistically significantly better with olanzapine ( mean + /- SE = 3.09 + /- 0.16 ) versus aripiprazole ( mean + /- SE = 3.74 + /- 0.15 ; p < .001 ) , and more subjects discontinued aripiprazole ( N = 32/88 ; 36 % ) than olanzapine ( N = 22/85 ; 26 % ) . CONCLUSION Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects , relative to uninterrupted continuation of olanzapine treatment . The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population OBJECTIVE This international , multicenter double-blind trial was design ed to compare the therapeutic profile of an atypical antipsychotic , olanzapine , with that of a conventional dopamine D2 antagonist , haloperidol . METHOD A total of 1,996 patients at 174 sites in Europe and North America were r and omly assigned to treatment with olanzapine ( N = 1,336 ) or haloperidol ( N = 660 ) over 6 weeks . The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale ( BPRS ) . Secondary analyses included comparisons of the mean change in positive and negative symptoms , comorbid depression , extrapyramidal symptoms , and overall drug safety . RESULTS Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure , including depression . Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events . Substantially more olanzapine-treated patients ( 66.5 % ) than haloperidol-treated patients ( 46.8 % ) completed 6 weeks of therapy . Statistically significant advantages of olanzapine treatment were related to 1 ) change in negative symptoms , 2 ) extrapyramidal symptom profile , 3 ) effect on prolactin levels , and 4 ) response rate . CONCLUSIONS Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology , with a substantially more favorable safety profile , than haloperidol . It meets several of the criteria for a novel atypical antipsychotic agent The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug . Thirty-six subjects with schizophrenia spectrum disorder , on conventional antipsychotic medication therapy for at least 2 years , were r and omized in double-blind fashion to risperidone versus olanzapine . Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated , followed by tapering and discontinuation of conventional antipsychotic medication . Atypical antipsychotic agents were then administered alone ( monotherapy ) for 12 weeks . Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression Scale , and Simpson Angus Scale . Body weight was measured at each visit . Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint ( 22 weeks ) [ risperidone : baseline=59.3 ( SE 3.1 ) , 22 weeks=44.3 ( SE 2.3 ) ( p<0.001 ) ; olanzapine : baseline=55.9 ( SE 3.3 ) , 22 weeks=46.9 ( SE 3.2 ) ( p<0.001 ) . Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts . Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression . Of note , while positive factor scores exhibited the majority of change within the first 10 weeks , negative factor scores continued to decline significantly in both treatment groups throughout the study . Tolerability assessment s did not differ between groups . The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents OBJECTIVE To demonstrate the efficacy of once-daily extended release quetiapine fumarate ( quetiapine XR ) versus placebo in adults with acute exacerbation of schizophrenia . METHODS A 6-week , double-blind , r and omized , placebo-controlled study . In- or out- patients with a DSM-IV diagnosis of schizophrenia were r and omized to fixed-dose quetiapine XR 400 , 600 , or 800 mg/day , quetiapine immediate release ( IR ) 800 mg/day , or placebo . Primary endpoint was change from baseline in Positive and Negative Syndrome Scale ( PANSS ) total score at Week 6 . Other efficacy assessment s included Clinical Global Impressions ( CGI ) of Severity ( CGI-S ) and of Improvement ( CGI-I ) ratings . Safety assessment s included adverse event ( AE ) reporting and laboratory measures . RESULTS 565 patients were r and omized ; 333 ( 58.9 % ) completed the study . Greater numeric improvements in PANSS total score were seen for quetiapine XR ( all doses ) and quetiapine IR versus placebo at Week 6 ; the differences were not statistically significant . Secondary efficacy endpoint results were similar . There was not a high placebo response in this study , but rather an attenuation of drug effect . In general , quetiapine XR was well tolerated over 6-weeks ' treatment ; there were no unexpected AEs . CONCLUSION The efficacy of quetiapine XR ( 400 , 600 , and 800 mg/day ) was not established at Week 6 . Quetiapine IR , an agent with established efficacy in schizophrenia , also did not separate from placebo at endpoint . Therefore , this is considered a failed study and possible reasons for this are discussed . Quetiapine XR was generally well tolerated and its safety profile was consistent with the known profile of quetiapine OBJECTIVE To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia . METHOD In this 8-week , double-blind , multicenter , flexible-dose study , patients with schizophrenia ( DSM-IV diagnosis ) were r and omly assigned to quetiapine ( 200 - 800 mg/day ) or risperidone ( 2 - 8 mg/day ) . The primary hypothesis was that quetiapine was not inferior to risperidone . The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale ( PANSS ) total scores ; secondary outcomes included response rate ( > or = 40 % reduction in PANSS scores ) , Clinical Global Impression-Change ( CGI-C ) , and cognitive and social functioning . Tolerability assessment s included treatment-emergent adverse events and changes in weight , glucose , and prolactin . Patients were recruited from June 2001 to September 2002 . RESULTS Patients ( N = 673 ) were r and omly assigned to quetiapine ( N = 338 , mean dose = 525 mg/day ) or risperidone ( N = 335 , mean dose = 5.2 mg/day ) . The primary analysis demonstrated noninferiority between treatments ( p < .05 ) . Improvements with both treatments were comparable on PANSS total , negative , and general psychopathology subscales . Risperidone-treated patients had a significantly ( p = .03 ) greater improvement in PANSS positive subscale score among all patients , but not among completers . Improvements in PANSS response rates , CGI-C , and cognitive function were similar between treatment groups . Changes in serum glucose and weight were minimal and comparable . The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone ( 22 % ) than quetiapine ( 13 % ; p < .01 ) . Somnolence was more common with quetiapine ( 26 % ) than risperidone ( 20 % ; p = .04 ) . Prolactin levels increased with risperidone ( + 35.5 ng/mL ) , but decreased with quetiapine ( -11.5 ng/mL ; p < .001 ) . CONCLUSIONS Quetiapine and risperidone had broadly comparable clinical efficacy . Both agents improved cognitive and social functioning , and neither had a clinical ly significant effect on weight or glucose . Somnolence was more common with quetiapine ; EPS and elevated prolactin rates were significantly higher with risperidone PURPOSE Although olanzapine may have advantages over other second-generation antipsychotics ( SGAs ) regarding longer time to treatment discontinuation among chronically ill patients , little evidence has been provided for the comparative effectiveness of SGAs in the acute phase . We aim ed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients . We performed a rater-blinded , r and omized controlled trial of four SGAs in 15 psychiatric emergency sites . Eligible patients were 18 - 64 years old and met diagnostic criteria for schizophrenia , acute schizophrenia-like psychotic disorder , or schizoaffective disorder . A final total of 78 patients were r and omly assigned by means of sealed envelopes to receive risperidone ( 3 - 12 mg/day ; n=20 ) , olanzapine ( 10 - 20 mg/day ; n=17 ) , quetiapine ( 300 - 750 mg/day ; n=20 ) , or aripiprazole ( 12 - 30 mg/day ; n=21 ) , with follow-up at 8 weeks . The primary outcome measure was all-cause treatment discontinuation . RESULTS Overall , 37 % ( 29/78 ) of patients discontinued the study medication before 8 weeks : 25 % for risperidone ; 12 % for olanzapine ; 55 % for quetiapine ; and 52 % for aripiprazole . Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine ( p=0.006 ) or aripiprazole ( p=0.008 ) groups , but not compared to the risperidone group ( p=0.32 ) . Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group ( p=0.048 ) , but not compared to the aripiprazole group ( p=0.062 ) . However , the rate of p.r.n . intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups ( p=0.029 ) . CONCLUSION Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients Treatment-emergent weight gain may be a general marker of therapeutic improvement , even when improvements occur in the absence of active antipsychotic treatment . To investigate the association between treatment-emergent weight gain and therapeutic improvement across placebo and active treatments , and to examine the association between reported treatment-emergent weight changes and the treatments ’ reported efficacy . Data from a r and omized , double-blind trial comparing treatment of schizophrenia with placebo and olanzapine were used to correlate weight change and change in psychopathology . Additionally , we correlated effect sizes of the efficacy of clozapine , olanzapine , risperidone , haloperidol and placebo ( reported in meta-analytical review s ) , with their reported weight changes . Weight gain significantly correlated with clinical improvements for placebo and olanzapine . The correlation between treatments ’ efficacy and corresponding weight changes was high ( r 0.88 , p 0.05 ) . Treatment-emergent weight gain appears to be an important marker of symptom reduction , and may not be exclusively attributable to pharmacological perturbations The primary objective of this study was to test the hypothesis that 1 or more dose levels of LY2140023 monohydrate , an oral prodrug of the potent metabotropic glutamate ( mGlu ) 2/3 receptor agonist LY404039 , given to patients with schizophrenia for 4 weeks would demonstrate significantly greater efficacy than placebo . The HBBI study was a multicenter , r and omized , double-blind , parallel , placebo- and active-controlled trial . Male and female patients aged 18 to 65 years who met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for schizophrenia were r and omized in a 2:2:2:2:2:1 ratio to receive 5- , 20- , 40- , or 80-mg LY2140023 monohydrate twice daily , placebo twice daily , or placebo ( am ) and 15 mg of olanzapine ( pm ) daily . Efficacy was defined as the change from baseline on the Positive and Negative Syndrome Scale ( PANSS ) total score assessed at 4 weeks . The primary analysis did not show that any of the 4 LY2140023 monohydrate doses were more efficacious than placebo as measured by the PANSS total score . Similarly , olanzapine did not significantly separate from placebo . A higher-than-anticipated treatment effect ( 14.6-point improvement ) in the placebo group was observed on PANSS total score . LY2140023 monohydrate was generally well tolerated , although 4 patients reported the serious adverse event of convulsion . LY2140023 monohydrate-treated patients showed little change in dopamine-related adverse events and weight . The results of the HBBI study are considered to be inconclusive because LY2140023 monohydrate and the active control olanzapine did not separate from placebo in the treatment of patients with acutely exacerbated schizophrenia . Additional efficacy , safety , and tolerability testing are needed OBJECTIVE The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies . The authors ' goal was to assess the effects of clozapine , olanzapine , risperidone , and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a r and omized double-blind 14-week trial . METHOD One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were in patients at four hospitals were originally included in the study . The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period . Planned assessment s included fasting glucose and cholesterol , which were collected at baseline and at the end of the 8-week period and the following 6-week period . RESULTS One hundred eight of the 157 patients provided blood sample s at baseline and at least at one point after r and om assignment to clozapine , olanzapine , risperidone , or haloperidol during the treatment trial . Seven of these patients had diabetes ; their glucose levels were > 125 mg/dl at baseline . Data from 101 patients were used for statistical analyses . During the initial 8-week period there was an overall significant increase in mean glucose levels . There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine ( N=27 ) and those given haloperidol ( N=25 ) . The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period ( N=22 ) . Fourteen of the 101 patients developed abnormal glucose levels ( > 125 mg/dl ) during the trial ( six with clozapine , four with olanzapine , three with risperidone , and one with haloperidol ) . Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine ( N=27 ) and those given olanzapine ( N=26 ) ; cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine ( N=22 ) . CONCLUSIONS In this prospect i ve r and omized trial , clozapine , olanzapine , and haloperidol were associated with an increase of plasma glucose level , and clozapine and olanzapine were associated with an increase in cholesterol levels . The mean changes in glucose and cholesterol levels remained within clinical ly normal ranges , but approximately 14 % of the patients developed abnormally high glucose levels during the course of their participation in the study BACKGROUND Paliperidone extended-release tablet ( paliperidone ER ; Invega , Janssen L.P. , Titusville , New Jersey ) is an oral psychotropic for schizophrenia treatment . METHODS Efficacy and safety of once-daily paliperidone ER ( 6 and 12 mg ) were assessed versus placebo in 444 patients with acute schizophrenia in a 6-week , multicenter , double-blind , r and omized , parallel-group study . An olanzapine ( 10 mg ) treatment arm was included to confirm trial validity . RESULTS Both doses of paliperidone ER demonstrated significant improvement in Positive and Negative Syndrome Scale ( PANSS ) total score ( p < or = .006 ) and certain PANSS Marder factor scores compared with placebo ( p < or = .025 ) ; PANSS total score also improved in the olanzapine treatment arm . Paliperidone ER 6 mg ( p < or = .008 ) , but not 12 mg , was associated with significant improvements in personal and social performance . The incidence of treatment-emergent adverse events ( AEs ) for paliperidone ER 6 mg was comparable with placebo and slightly greater with paliperidone ER 12 mg . Changes in blood glucose and lipid levels with paliperidone ER were comparable with placebo . Two patients treated with paliperidone ER experienced glucose-related AEs . Body-weight increases of 1 - 2 kg were observed with paliperidone ER . Although there were increases in plasma prolactin levels with paliperidone ER treatment , the incidence of prolactin-related AEs was < or = 1 % . CONCLUSIONS In this study , paliperidone ER , particularly the 6-mg dose , was effective and well tolerated , and provides a valuable new treatment option for schizophrenia OBJECTIVE To better underst and the efficacy and tolerability of atypical antipsychotics among racial groups , we review ed data from four short-term ( 4 - 6 weeks ) , fixed-dose , placebo-controlled trials of ziprasidone for black , white , and overall population s of patients with schizophrenia . METHODS Efficacy of ziprasidone in the black , white , and overall schizophrenic population s was compared to placebo using st and ard efficacy measures ( Positive and Negative Syndrome Scale [ PANSS ] total , PANSS negative , Brief Psychiatric Rating Scale [ BPRS ] , Clinical Global Impression-Severity [ CGI-S ] , CGI-Improvement [ CGI-I ] ) . RESULTS Black patients receiving ziprasidone demonstrated statistically significant improvements from baseline in PANSS total , PANSS negative , and BPRS , and improvements in CGI-S and CGI-I ( n=99 - 149 ) compared with placebo ( n=41 - 66 ) ; improvements were comparable to those observed in the overall population ( n=451 - 639 ) and the white population ( n=310 - 430 ) . Interaction effect ( treatment by race ) was not significant for any efficacy variables . Ziprasidone was well-tolerated among black patients ( n=175 ) . Adjusted mean ( least squares mean ) overall weight gain in black patients receiving ziprasidone ( n=124 ) was 1.8 kg . There were no increases in total cholesterol , triglycerides , or r and om glucose in the black population . CONCLUSION Ziprasidone has similar efficacy and safety in black patients with schizophrenia compared with patients in the white and overall population OBJECTIVE Asian population s may differ from other races in response to antipsychotics . Studies of aripiprazole in Asian population s are scarce . This study aim ed to investigate the efficacy , safety , and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder . METHOD This 4-week , double-blind , r and omized , parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005 . A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were r and omly assigned ( with a r and omization ratio of 3:2 ) to 15 mg/day of aripiprazole ( N = 49 ) or 6 mg/day of risperidone ( N = 34 ) . Efficacy measures included the Positive and Negative Syndrome Scale ( PANSS ) total , positive , and negative scores and Clinical Global Impressions-Severity of Illness ( CGI-S ) and -Improvement scale scores . Extrapyramidal symptoms ( EPS ) , weight gain , serum prolactin level , QTc interval , and self-reported adverse events were assessed as measures of safety and tolerability . RESULTS Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total , PANSS positive , PANSS negative , and CGI-S scores at study endpoint ( all p < .001 ) . Significant improvement was noted in the first week of treatment for both treatment groups . There were no significant differences in efficacy measures between treatment groups . Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale ( p < .005 ) and less serum prolactin level elevation ( p < .001 ) than risperidone . Both groups showed mild weight gain . No patients showed clinical ly significant QTc interval prolongation in this study . CONCLUSION Compared with risperidone 6 mg/day , aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia . In this group of Chinese patients , the overall response to aripiprazole did not differ from that of white patients . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00283179 BACKGROUND Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors . This multicenter trial examined the efficacy , safety , and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder . METHODS In this 4-week double-blind study , 404 patients were r and omized to 20 mg/d ( n = 101 ) or 30 mg/d ( n = 101 ) of aripiprazole , placebo ( n = 103 ) , or 6 mg/d of risperidone ( n = 99 ) . Efficacy assessment s included Positive and Negative Syndrome Scale ( PANSS ) scores and Clinical Global Impression scores . Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight , prolactin , and corrected QT ( QTc ) interval . RESULTS Aripiprazole ( 20 and 30 mg/d ) and risperidone ( 6 mg/d ) were significantly better than placebo on all efficacy measures . Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole . There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales . Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone . Mean change in QTc interval did not differ significantly from placebo with any active treatment group . Aripiprazole and risperidone groups showed a similar low incidence of clinical ly significant weight gain . CONCLUSIONS Aripiprazole is effective , safe , and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder . It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders We examined whether clozapine-related weight gain is associated with an increase in mean arterial blood pressure . Weight gain and mean arterial blood pressure changes were assessed in 61 out patients with schizophrenia who were r and omly assigned to either clozapine or haloperidol in a 10-week parallel group , double-blind study and in 55 patients who chose to continue to receive clozapine in a subsequent 1-year open-label prospect i ve study . Clozapine treatment was associated with significant weight gain in the double blind and open-label trials . Haloperidol treatment was not associated with significant weight gain . Neither clozapine nor haloperidol treatment were associated with significant changes in mean arterial blood pressure . There were no significant correlations between weight gain and mean arterial blood pressure change with either medication . Although clozapine treatment is associated with weight gain , the correlation between this weight gain and increases in arterial blood pressure during the first year of treatment appears to be low BACKGROUND Paliperidone extended-release tablet ( paliperidone ER ) is an investigational oral psychotropic developed for schizophrenia treatment . It utilizes OROS technology to provide a unique pharmacokinetic profile , eliminating the need for titration and potentially leading to improved tolerability . Furthermore , paliperidone undergoes limited hepatic metabolism . METHODS The efficacy and safety of once-daily paliperidone ER ( 6 mg , 9 mg and 12 mg ) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week , multicenter , double-blind , r and omized , parallel-group study . RESULTS All doses of paliperidone ER demonstrated significant improvement in PANSS score , all PANSS Marder factor scores ( p<0.001 ) and personal and social functioning versus placebo ( p<0.001 ) . The PANSS total score also improved significantly in the olanzapine treatment arm . Significantly higher percentages of paliperidone ER patients demonstrated a > or = 30 % reduction in PANSS total score versus placebo ( p<0.001 ) . The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups . In the paliperidone ER groups there were no reports of glucose-related AEs or clinical ly relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg . CONCLUSION In this study , all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated . Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia OBJECTIVE The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization . METHOD In a 6-week double-blind study , in patients with a recent exacerbation of schizophrenia were r and omly assigned to treatment with paliperidone extended-release , quetiapine , or placebo . A 2-week monotherapy phase was followed by a 4-week additive-therapy phase . Target doses were at the upper end of recommended ranges : paliperidone extended-release , 9 or 12 mg/day , and quetiapine , 600 or 800 mg/day . The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale ( PANSS ) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint . RESULTS Six-week completion rates were 77.5 % ( 124/160 ) with paliperidone extended-release , 66.7 % ( 106/159 ) quetiapine , and 63.8 % ( 51/80 ) placebo . Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 ( -11.4 versus -8.2 ) through the monotherapy phase endpoint ( -23.4 versus -17.1 ) . Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks . At the 6-week study endpoint , there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy ( predominantly other antipsychotics ) . Common adverse events with paliperidone extended-release , quetiapine , and placebo , respectively , were tremor ( 13.9 % , 5.0 % , 7.5 % ) , somnolence ( 8.9 % , 11.9 % , 1.3 % ) , insomnia ( 10.1 % , 9.4 % , 11.3 % ) , and headache ( 12.0 % , 7.5 % , 13.8 % ) . Six-week adverse event-related discontinuation rates were 6.3 % , 10.1 % , and 6.3 % , respectively , in the paliperidone extended-release , quetiapine , and placebo groups . CONCLUSIONS Compared with quetiapine , paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization , with no unexpected tolerability findings Abstract Problems with the efficacy of second-generation antipsychotics on negative symptoms and cognition have highlighted the need for further development of drugs targeting central nervous system neurotransmitter systems other than dopamine . One target in development is neurokinin 3 ( NK3 ) tachykinin receptors , which are coreleased and interact with dopamine . This study investigates the efficacy , tolerability , and cognitive effects of AZD2624 , a selective , orally active NK3 receptor antagonist , in symptomatic patients with schizophrenia . Patients were r and omly assigned to 1 of 3 treatment groups : AZD2624 40 mg , placebo , or olanzapine 15 mg . Treatment lasted for 28 days , and the Positive and Negative Syndrome Scale , the Clinical Global Impression Severity Scale and Improvement Scales , and cognition as assessed by CogState were used as primary outcome measures . There were no significant differences in patients treated with AZD2624 versus placebo on change in Positive and Negative Syndrome Scale total score and Clinical Global Impression Severity Scale ; in addition , no change in CogState measures was found . Results of the trial do not support a role for the NK3 antagonist AZD2624 as a therapeutic treatment for acute schizophrenia when used as monotherapy OBJECTIVE The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice . METHOD Subjects ( N=377 ) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were r and omly assigned to receive 2 - 6 mg/day of risperidone ( mean modal dose=4.8 mg/day ) or 5 - 20 mg/day of olanzapine ( mean modal dose=12.4 mg/day ) for 8 weeks . RESULTS The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group . Seventy-five percent of the participants completed the trial , with no between-treatment differences in the proportion of dropouts . Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms ( 24 % and 20 % , respectively ) . Severity of extrapyramidal symptoms was low in both groups , with no between-group differences . Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 ( subjects who completed the study ) and endpoint ( all subjects , including dropouts ) . There were overall between-treatment differences in efficacy . Comparison of individual factors found no significant differences at endpoint ; at week 8 , however , improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine . An increase in body weight of > or = 7 % was seen in 27 % of olanzapine participants and 12 % of risperidone participants . CONCLUSIONS Both treatments were well tolerated and efficacious . The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups . Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers . There was no measure on which olanzapine was superior . Greater weight gain was associated with olanzapine than with risperidone treatment OBJECTIVE The authors compared the effects of the two most commonly used atypical antipsychotics , risperidone and olanzapine , in elderly patients with schizophrenia . METHODS In an 8-week , international , double-blind study , patients ( out patients , hospital in patients , and residents of nursing or boarding homes ) were r and omly assigned to receive risperidone ( 1 mg to 3 mg/day ) or olanzapine ( 5 mg to 20 mg/day ) . The main outcome measures were changes in Positive and Negative Syndrome Scale ( PANSS ) total scores and rates of extrapyramidal symptoms ( EPS ) . RESULTS Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder . The mean duration of illness was 36.5 years . Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine . PANSS total scores and four of the five PANSS factor scores ( positive symptoms , negative symptoms , disorganized thoughts , and anxiety/depression ) improved significantly at all time-points and at endpoint in both groups ; between-treatment differences were not significant . EPS-related adverse events were reported by 9.2 % of patients in the risperidone group and 15.9 % in the olanzapine group ; the between-treatment difference was not significant . Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint ; between-treatment differences were not significant . Clinical ly relevant weight gain was seen in both groups , but was significantly less frequent in risperidone patients than in olanzapine patients . CONCLUSIONS Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms , with a relatively low risk of side effects AIM To assess changes in insulin sensitivity in non-diabetic adults with schizophrenia or schizoaffective disorder treated with olanzapine or risperidone . METHODS One hundred and thirty patients were r and omly assigned to 12 weeks double-blind treatment with olanzapine or risperidone . Insulin sensitivity was measured using a two-step euglycaemic , hyperinsulinaemic clamp procedure . Whole-body adiposity was measured using dual-energy X-ray absorptiometry . The primary endpoint was the within-group change from baseline in insulin sensitivity normalized to fat-free mass ( M(ffm ) /I ) during the clamp procedure 's low-insulin phase , using an analysis of covariance model including the covariate weight change . RESULTS Forty-one olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements . Mean M(ffm ) /I during the low-insulin phase declined 9.0 % ( p = 0.226 ) in olanzapine-treated patients and 13.2 % ( p = 0.047 ) in risperidone-treated patients ( between-group difference p = 0.354 ) . During the high-insulin phase , M(ffm ) /I declined 10.4 % ( p = 0.036 ) in olanzapine-treated patients and 2.1 % ( p = 0.698 ) in risperidone-treated patients ( between-group difference p = 0.664 ) . Changes in M(ffm ) /I correlated inversely with changes in body weight and adiposity , which were generally higher in olanzapine-treated patients . Significant within-group increases in fasting glucose , but not haemoglobin A1c ( HbA1c ) , were observed during olanzapine treatment . The fasting glucose change was not correlated with M(ffm ) /I changes . CONCLUSIONS Small , but statistically significant , decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested . Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients . Changes in insulin sensitivity correlated significantly with changes in weight or adiposity , but not with changes in glucose OBJECTIVE The presence of obesity and increases in body mass are important risk factors for cardiovascular disease and diabetes . This study examined the effects of olanzapine , risperidone , and haloperidol on weight , body mass index ( BMI ) , and development of obesity in a drug-naive population compared with a matched healthy control group . METHOD Consecutive patients during the period from June through October 2006 with DSM-IV schizophrenia at our referral psychiatric hospital were recruited for an extensive prospect i ve study that included anthropometric measures of weight , waist circumference , waist-hip ratio , and BMI . Subjects were r and omly assigned to receive haloperidol , olanzapine , or risperidone and compared with a matched healthy control group . The prevalence of obesity , which was the main outcome measure , was assessed on the basis of 2 criteria : revised World Health Organization ( WHO ) definition for Asians and criteria of the International Diabetes Federation ( IDF ) . Inclusion s started in June 2006 , and patients were followed for a period of 6 weeks . RESULTS The analysis of 66 patients showed a prevalence of overweight ( WHO criteria ) at 22.7 % and obesity at 31.8 % ( IDF criteria ) . The prevalence of obesity ( IDF criteria ) in our patients is over 30 times as high as that of the matched healthy control group ( p < .001 ) . Subjects in the olanzapine group had the greatest weight gain at 5.1 kg , followed by risperidone at 4.1 kg and haloperidol at 2.8 kg . CONCLUSIONS Obesity is highly prevalent among patients treated with atypical antipsychotics for schizophrenia . Assessment and monitoring of obesity along with preventive and curative measures should be part of the clinical management of patients treated with antipsychotics . TRIAL REGISTRATION Clinical Trials.gov , NCT00534183 , www . clinical trials.gov Abstract This phase III study evaluated the efficacy and safety of cariprazine , a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors , in patients with acute exacerbation of schizophrenia . Patients were r and omized to 6-week double-blind treatment with placebo , cariprazine 3 to 6 mg/d , or cariprazine 6 to 9 mg/d . Primary and secondary efficacy : change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores , respectively , analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons . Safety included treatment-emergent adverse events , clinical laboratory values , vital signs , electrocardiograms , ophthalmologic examination , Columbia-Suicide Severity Rating Scale , and extrapyramidal symptom scales . In the Safety Population ( placebo , n = 147 ; cariprazine 3–6 mg/d , n = 151 ; cariprazine 6–9 mg/d , n = 148 ) , 60.5 % of patients completed the study . At week 6 , statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score ( 3–6 mg/d : −6.8 , P = 0.003 ; 6–9 mg/d : −9.9 , P < 0.001 ) and Clinical Global Impressions-Severity ( 3–6 mg/d : −0.3 , P = 0.012 ; 6–9 mg/d : −0.5 , P < 0.001 ) . Common treatment-emergent adverse events ( ≥5 % and twice the rate of placebo ) in both cariprazine groups were akathisia , extrapyramidal disorder , and tremor ; most were mild to moderate in severity . Mean changes in metabolic parameters were generally small and similar between groups . Prolactin levels decreased in all groups . In conclusion , cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters . Cariprazine was generally well tolerated . These results suggest that cariprazine may be a new and effective treatment for schizophrenia With the notable exception of clozapine , there is at present insufficient information on the efficacy of atypical antipsychotic medications in patients with poorly responsive schizophrenia . The present study reports on the efficacy and tolerability of quetiapine and haloperidol in patients with schizophrenia who showed no response to treatment with fluphenazine . This study is a post hoc sub analysis of an 8-week , double-blind study of patients receiving quetiapine 600 mg/day or haloperidol 20 mg/day . The proportion of patients classified as " Clinical Global Impression responders " ( defined as Clinical Global Impression Severity of Illness score of < or = 3 at study end ) was greater in the quetiapine group compared with the haloperidol group ( 51 % vs. 25 % ; P = 0.023 ) . Overall , quetiapine was well tolerated with less extrapyramidal side-effects and reduction in prolactin when compared to haloperidol . Weight gain was modest but more apparent in quetiapine-treated patients . Quetiapine is an appropriate treatment choice in patients who do not respond to prior antipsychotic treatment OBJECTIVE The atypical antipsychotic olanzapine has extensively been compared with haloperidol , whereas studies vs. other ( conventional ) neuroleptics are scarce . This exploratory double-blind 4-week study was design ed to compare the efficacy and the safety of olanzapine ( OLA ) and flupenthixol ( FLU ) which have recently been considered as a " partially atypical " antipsychotics . METHODS Twenty-eight in patients with schizophrenia ( DSM-IV ) were r and omly assigned for treatment with OLA ( N = 15 , 5 - 20 mg/d ) or FLU ( N = 13 , 5 - 20 mg/d ) . The Brief Psychiatric Rating Scale ( BPRS ) and the Negative Symptoms Rating Scale ( NSRS ) , plus the Patient Global Impression ( PGI ) and Clinical Global Impression ( CGI ) scales , were used to assess the efficacy of both compounds ; safety was determined by using the Simpson Angus Scale ( SAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) and by assessing treatment-emergent adverse events . Non-parametric statistics were applied . RESULTS BPRS and NSRS scores improved in both groups ( exploratory tests ; all p < or = 0.02 ) . Similar results were observed for CGI-Severity , CGI- and PGI-Improvement . There were no significant group differences . Responder rates ( at least 40 % decrease in BPRS total ) were 9/13 OLA patients ( 69 % ) and 9/12 FLU patients ( 75 % ) . EPS events were reported only in the FLU group ( p < 0.01 ) ; FLU patients needed significantly more anticholinergic medication . Weight gain was higher in OLA patients ( p < 0.01 ) . Overall , fewer patients with adverse events were observed in the OLA group ( p = 0.04 ) . No significant changes were noted on SAS and AIMS scores . CONCLUSION Findings from this study suggest that overall and negative symptomatology improved in both treatment groups , while the safety and tolerability profiles differed for both substances OBJECTIVE To examine the efficacy and tolerability of a new injectable formulation of olanzapine , olanzapine long-acting injection ( LAI ) , relative to placebo for treatment of acutely ill patients with schizophrenia . METHOD Patients with DSM-IV or DSM-IV-TR schizophrenia in this 8-week , double-blind study were r and omly assigned to receive 210 mg/2 weeks , 300 mg/2 weeks , or 405 mg/4 weeks of olanzapine LAI or placebo/2 weeks . No oral antipsychotic supplementation was permitted . The primary efficacy measure was mean baseline-to-end point change in Positive and Negative Syndrome Scale ( PANSS ) total score . The study was conducted from June 2004 to April 2005 . RESULTS Mean baseline-to-end point decreases in PANSS total scores were significantly greater for all olanzapine LAI regimens relative to placebo ( all p values < .001 ) . The 300 mg/2 weeks and 405 mg/4 weeks olanzapine LAI groups separated from placebo on the PANSS total at 3 days after starting treatment , and all olanzapine LAI groups separated from placebo by 7 days . Rates of clinical improvement ( end point Clinical Global Impressions-Improvement scale score < or= 3 ) were significantly higher for all olanzapine LAI groups relative to placebo ( p < .001 ) . Incidences of sedation and increased appetite were significantly higher for 300 mg/2 weeks olanzapine LAI relative to placebo ( p < .05 ) . Mean weight gain ( 3.2 - 4.8 vs. 0.3 kg , p < .001 ) and incidence of weight gain > or= 7 % of baseline ( 23.6 - 35.4 % vs. 12.4 % , p < or= .046 ) were significantly greater for olanzapine LAI relative to placebo . Significant differences between all olanzapine LAI groups and placebo were observed regarding mean baseline-to-end point changes in fasting total cholesterol ( 5.5 - 10.4 vs. -7.0 mg/dL ; p < or= .015 ) and between the 210 mg/2 weeks and 405 mg/4 weeks groups ( 26.3 - 30.3 vs. -9.4 mg/dL ; p < or= .016 ) , but not the 300 mg/2 weeks group ( 17.6 mg/dL ; p = .055 ) , and placebo for fasting triglycerides . CONCLUSIONS In this 8-week study , olanzapine LAI administered at 2- or 4-week injection intervals was significantly more efficacious than placebo for the treatment of acutely ill patients with schizophrenia despite no use of supplemental oral antipsychotics . Consistent with changes previously observed with oral olanzapine , clinical ly significant weight gain and changes in some lipid parameters were observed in patients treated with olanzapine LAI OBJECTIVE The efficacy and safety of olanzapine were compared with those of ziprasidone . METHOD This was a multicenter r and omized , double-blind , parallel-group , 28-week study of patients with schizophrenia . Patients were r and omly assigned to treatment with 10 - 20 mg/day of olanzapine or 80 - 160 mg/day of ziprasidone . The primary efficacy measure was the Positive and Negative Syndrome Scale total score . Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood , quality of life , and extrapyramidal symptom scales . Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight . RESULTS The study was completed by significantly more olanzapine-treated patients ( 165 of 277 , 59.6 % ) than ziprasidone-treated patients ( 115 of 271 , 42.4 % ) . At 28 weeks , the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement . The responder rate was higher for olanzapine than for ziprasidone . Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses , but results favored olanzapine on baseline-to-maximum changes . Weight change was significantly greater with olanzapine ( mean=3.06 kg , SD=6.87 ) than with ziprasidone ( mean=-1.12 kg , SD=4.70 ) . Fasting lipid profiles were significantly superior in the ziprasidone group ; there was no significant difference in fasting glucose level . CONCLUSIONS Olanzapine treatment result ed in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment , while ziprasidone was superior for weight change and lipid profile BACKGROUND AND PURPOSE The atypical antipsychotics , amisulpride and risperidone , have different receptor affinity characteristics . Although the relative efficacy of both drugs compared to conventional antipsychotics is well established , it remains unclear how the efficacy of amisulpride compares with risperidone . There have been no controlled studies comparing amisulpride to risperidone in Asian patients . The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients . METHODS Patients with productive positive symptoms ( n = 48 ) were enrolled into this double-blind , r and omized pilot study for 6 weeks . Patients received either amisulpride ( 400 - 800 mg/day ) or risperidone ( 4 - 8 mg/day ) . Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression ( CGI ) , Social and Occupational Functioning Assessment Scale ( SOFAS ) , and patients ' subjective responses to treatment were assessed during the trial period . Adverse events were recorded at each follow-up visit . RESULTS At the end of the trial , the mean dosage was 630 + /- 134 mg/day and 6.88 + /- 1.54 mg/day for amisulpride and risperidone , respectively . There was no significant difference in the reduction of the PANSS total score ( amisulpride -24.1 versus risperidone -28.4 , p = 0.999 ) , the PANSS positive subscale score ( amisulpride -6.8 versus risperidone -8.3 , p = 0.467 ) , the PANSS negative subscale score ( amisulpride -5.6 versus risperidone -6.4 , p = 0.999 ) , or the CGI score between the two groups . The extrapyramidal symptom ratings , the improvement in the SOFAS ( amisulpride 11.1 versus risperidone 10.0 ) and the subjective response ( amisulpride 82 % versus risperidone 83 % ) were comparable . No serious adverse events were recorded in either treatment group . There was a statistically significant body weight gain in the risperidone group . In contrast , there was a statistically , though not clinical ly , significant reduction of blood pressure and heart rate in the amisulpride group . CONCLUSIONS This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia . Both drugs were well tolerated , but had different side effect profiles The objective of this study was to compare the effects of risperidone and olanzapine in schizophrenic patients with intolerant extrapyramidal side effects ( EPS ) on first generation antipsychotics . We conducted an 8-week , rater-blinded , flexible dose study . Seventy patients with schizophrenia , who met the DSM-IV research criteria of having neuroleptic-induced acute dystonia or parkinsonism , were r and omly assigned to risperidone or olanzapine group . The primary outcome was a comparison of the incidence of concomitant anticholinergic drugs usage between the groups to manage their acute dystonia and parkinsonism . The average doses of risperidone and olanzapine from baseline to study end point were 1.8—3.5 mg/day and 7.7—11.7 mg/day , respectively . There were no significant differences in demographic data , severity of EPS or psychotic symptoms between the groups at baseline assessment . Patients taking risperidone had significantly higher incidence of using anticholinergic drugs to manage acute dystonia or parkinsonism overall during the study ( OR = 5.17 , 95%CI = 1.49—17.88 , P = 0.013 ) . There was no significant between-group difference in the changing of rating scales of EPS and psychotic symptoms . The results of our study favour olanzapine as a better choice in schizophrenic patients with intolerant EPS . Double-blinded , fixed dose and different ethnical study for EPS-intolerant schizophrenic patients is needed to confirm the results of our study Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features . In a double-blind 6-week trial , 458 patients with acute schizophrenia were r and omly assigned to fixed-dose treatment with asenapine at 5 mg twice daily ( BID ) , asenapine at 10 mg BID , placebo , or haloperidol at 4 mg BID ( to verify assay sensitivity ) . With last observations carried forward ( LOCF ) , mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID ( −16.2 ) and haloperidol ( −15.4 ) than placebo ( −10.7 ; both P < 0.05 ) ; using mixed model for repeated measures ( MMRM ) , changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID ( −21.3 and −19.4 , respectively ) and haloperidol ( −20.0 ) than placebo ( −14.6 ; all P < 0.05 ) . On the Positive and Negative Syndrome Scale positive subscale , all treatments were superior to placebo with LOCF and MMRM ; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM . Treatment-related adverse events ( AEs ) occurred in 44 % and 52 % , 57 % , and 41 % of the asenapine at 5 and 10 mg BID , haloperidol , and placebo groups , respectively . Extrapyramidal symptoms reported as AEs occurred in 15 % and 18 % , 34 % , and 10 % of the asenapine at 5 and 10 mg BID , haloperidol , and placebo groups , respectively . Across all groups , no more than 5 % of patients had clinical ly significant weight change . Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol ; greater contrasts were seen in AEs , especially extrapyramidal symptoms |
2,339 | 17,651,477 | Conclusion A number of empathy measures available have been psychometrically assessed for research use among medical students and practising medical doctors .
No empathy measures were found with sufficient evidence of predictive validity for use as selection measures for medical school . | Background Empathy is frequently cited as an important attribute in physicians and some groups have expressed a desire to measure empathy either at selection for medical school or during medical ( or postgraduate ) training .
In order to do this , a reliable and valid test of empathy is required .
The purpose of this systematic review is to determine the reliability and validity of existing tests for the assessment of medical empathy . | CONTEXT Medical errors are associated with feelings of distress in physicians , but little is known about the magnitude and direction of these associations . OBJECTIVE To assess the frequency of self-perceived medical errors among resident physicians and to determine the association of self-perceived medical errors with resident quality of life , burnout , depression , and empathy using vali date d metrics . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic Rochester . Data were provided by 184 ( 84 % ) of 219 eligible residents . Participants began training in the 2003 - 2004 , 2004 - 2005 , and 2005 - 2006 academic years and completed surveys quarterly through May 2006 . Surveys included self- assessment of medical errors and linear analog scale assessment of quality of life every 3 months , and the Maslach Burnout Inventory ( depersonalization , emotional exhaustion , and personal accomplishment ) , Interpersonal Reactivity Index , and a vali date d depression screening tool every 6 months . MAIN OUTCOME MEASURES Frequency of self-perceived medical errors was recorded . Associations of an error with quality of life , burnout , empathy , and symptoms of depression were determined using generalized estimating equations for repeated measures . RESULTS Thirty-four percent of participants reported making at least 1 major medical error during the study period . Making a medical error in the previous 3 months was reported by a mean of 14.7 % of participants at each quarter . Self-perceived medical errors were associated with a subsequent decrease in quality of life ( P = .02 ) and worsened measures in all domains of burnout ( P = .002 for each ) . Self-perceived errors were associated with an odds ratio of screening positive for depression at the subsequent time point of 3.29 ( 95 % confidence interval , 1.90 - 5.64 ) . In addition , increased burnout in all domains and reduced empathy were associated with increased odds of self-perceived error in the following 3 months ( P=.001 , P<.001 , and P=.02 for depersonalization , emotional exhaustion , and lower personal accomplishment , respectively ; P=.02 and P=.01 for emotive and cognitive empathy , respectively ) . CONCLUSIONS Self-perceived medical errors are common among internal medicine residents and are associated with substantial subsequent personal distress . Personal distress and decreased empathy are also associated with increased odds of future self-perceived errors , suggesting that perceived errors and distress may be related in a reciprocal cycle The inability to cope successfully with the enormous stress of medical education may lead to a cascade of consequences at both a personal and professional level . The present study examined the short-term effects of an 8-week meditation-based stress reduction intervention on premedical and medical students using a well-controlled statistical design . Findings indicate that participation in the intervention can effectively ( 1 ) reduce self-reported state and trait anxiety , ( 2 ) reduce reports of overall psychological distress including depression , ( 3 ) increase scores on overall empathy levels , and ( 4 ) increase scores on a measure of spiritual experiences assessed at termination of intervention . These results ( 5 ) replicated in the wait-list control group , ( 6 ) held across different experiments , and ( 7 ) were observed during the exam period . Future research should address potential long-term effects of mindfulness training for medical and premedical students CONTEXT It has been reported that medical students become more cynical as they progress through medical school . This can lead to a decline in empathy . Empirical research to address this issue is scarce because the definition of empathy lacks clarity , and a tool to measure empathy specifically in medical students and doctors has been unavailable . OBJECTIVE To examine changes in empathy among medical students as they progress through medical school . MATERIAL S AND SUBJECTS A newly developed scale ( Jefferson Scale of Physician Empathy [ JSPE ] , with 20 Likert-type items ) was administered to 125 medical students at the beginning ( pretest ) and end ( post-test ) of Year 3 of medical school . This scale was specifically developed for measuring empathy in patient care situations and has acceptable psychometric properties . METHODS In this prospect i ve longitudinal study , the changes in pretest/post-test empathy scores were examined by using t-test for repeated measure design ; the effect size estimates were also calculated . RESULTS Statistically significant declines were observed in 5 items ( P < 0.01 ) and the total sores of the JSPE ( P < 0.05 ) between the 2 test administrations . CONCLUSIONS Although the decline in empathy was not clinical ly important for all of the statistically significant findings , the downward trend suggests that empathy could be amenable to change during medical school . Further research is needed to identify factors that contribute to changes in empathy and to examine whether targeted educational programmes can help to retain , reinforce and cultivate empathy among medical students for improving clinical outcomes BACKGROUND Empathy is critical to the development of professionalism in medical students , and the humanities-particularly literature -have been touted as an effective tool for increasing student empathy . This quantitative/qualitative study was undertaken to assess whether reading and discussing poetry and prose related to patients and doctors could significantly increase medical student empathy and appreciation of the relevance of the humanities for their own professional development . METHOD In 2000 - 2001 , first year students ( n=22 ) volunteered for an eight-session literature and medicine elective and were r and omly assigned to either immediate participation in the class or a wait-list group , who participated in the same class 6 months later . Complete pre- and post-intervention data for 16 students from both groups were obtained for two quantitative measures of empathy and an attitudes-toward-the-humanities scale . Students also participated in a qualitative group interview pre- and post-intervention . RESULTS Empathy and attitudes toward the humanities improved significantly ( p<0.01 ) after participation in the class when both groups of students were combined . The scaled treatment effect size was in the moderate range ( > or = 0.60 st and ard deviation units ) for both measures that had statistically significant pre-to-post changes . Furthermore , student underst and ing of the patient 's perspective became more detailed and complex after the intervention . Students were also more likely post-intervention to note ways reading literature could help them cope with training-related stress . CONCLUSION A brief literature -based course can contribute to greater student empathy and appreciation for the value of humanities in medical education 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 Medical education faces increasing criticism because of the perception that it is difficult to produce physicians who are both technically competent and compassionate . One approach to addressing this problem is to train physicians to address the emotional concerns that patients experience as a result of their medical problems . Results of the authors ' r and omized , controlled experiment in training medical students to respond to patients ' emotional concerns provide evidence of the efficacy and feasibility of such training . Only students who received small-group instruction in addition to large-group lectures exhibited statistically significant ( p less than .001 ) improvement in their ability to respond to the emotional concerns of patients in hypothetical cases . The students who received only the lectures exhibited significant improvement ( p less than .001 ) in their preference for responses that addressed patients ' emotional concerns but not in their responses to written , hypothetical patient cases . Even though these students ' preferences for responses to emotional concerns on the average did increase significantly , the preferences were significantly ( p less than .001 ) less favorable than the preferences of the students who received small-group instruction . The small group instruction consisted of both interviews with elderly nursing home residents , who served as simulated patients , and structured practice and review sessions Summary Practitioner empathy and patient enablement at a " contact " consultation were retrospectively associated with changes in main complaint and well-being , in a cross-sectional study of out- patients attending the Glasgow Homoeopathic Hospital . Patient expectation , relational continuity , and duration of attendance at the hospital were also correlated with perceived change in health outcome in univariate analysis . However , multi-regression analysis suggested three major independent variables associated with health outcome – empathy , enablement , and duration of attendance . Health outcomes were then measured in the same cohort 12 months after " contact " consultation . Both univariate and multivariate analysis indicated that the only significant predictive factor in health change over the 12-month period was patient enablement score at contact consultation . This study demonstrates the importance of prospect i ve studies in assessing potentially causal relationships between consultation quality and health outcomes and suggests a key role for patient enablement . ZusammenfassungIn einer Querschnittsstudie wurden ärztliche Empathie und Patienten-"Enablement " bei ambulanter Erstkonsultation am Glasgow Homeopathic Hospital retrospektiv auf ihre Auswirkung auf Hauptbeschwerden und Wohlbefinden untersucht . Die Erwartung der Patienten , Kontinuität der Betreuung und Dauer der Betreuung wurden ebenso mit Änderungen i m Befinden korreliert . In der Multiregressionsanalyse sind 3 wesentliche unabhängige Faktoren mit dem Outcome assoziiert – Empathie , Enablement und Betreuungsdauer . Outcome -Parameter wurden anschließend in der gleichen Kohorte 12 Monate nach Erstkonsultation untersucht . Sowohl in der univariaten als auch der multivariaten Analyse war der einzige Faktor mit signifikanter Auswirkung auf das Outcome nach 12 Monaten der Patienten-"Enablement"-Score bei Erstkonsultation . Die Studie zeigt die Wichtigkeit prospektiver Untersuchungen , um kausale Zusammenhänge zwischen der Qualität einer Konsultation und dem Outcome zu erfassen , und legt eine Schlüsselrolle für den Faktor Patienten-"Enablement " nahe OBJECTIVE To relate prospect ively initial consultation characteristics-length , empathy , and patient enablement- with perceived health changes in patients going to the Glasgow Homoeopathic Hospital ( GHH ) . METHODS Consecutive out patients completed the Consultation and Relational Empathy ( CARE ) measure and the Patient Enablement Instrument ( PEI ) immediately after their first consultations , again at 3 months , and the PEI also at 12 months . The Short Form-12 was completed immediately before and the Measure Yourself Medical Outcome ( MYMOP ) Profile during the first consultation , and both were repeated at 3 and 12 months . Perceived changes in main complaint and well-being were assessed using the Glasgow Homoeopathic Outcome Scale ( GHHOS ) . RESULTS Empathy score at first consultation was highly predictive of ongoing empathy score at 3 months ( Spearman 's rho , 0.572 , p < 0.0001 ) . Empathy scores at first consultation also correlated significantly with enablement score at first consultation ( rho , 0.325 , p < 0.0001 ) and overall enablement at 12 months ( rho , 0.281 ; p < 0.05 ) . Controlling for the number of subsequent consultations , initial empathy scores were also predictive of change in main complaint , and general well-being , at 3 months ( rho , 0.225 , 0.213 respectively ; p < 0.05 ) . Enablement score at first consultation also predicted overall enablement at 3 months ( rho , 0.255 ; p < 0.05 ) and 12 months ( rho , 0.282 ; p < 0.05 ) . Initial enablement predicted GHOSS well-being score at 3 months after controlling for number of consultations ( rho , 0.279 ; p < 0.05 ) . Both empathy and enablement at 3 months predicted overall enablement at 12 months ( rho , 0.327 ; p < 0.01 and rho , 0.577 ; p < 0.0001 , respectively ) . Empathy at 3 months was not significantly related to GHHOS scores at 12 months , whereas enablement scores at 3 months were highly predictive of both GHHOS main complaint and well-being scores at 12 months ( rho , 0.459 and 0.507 , respectively ; p < 0.0001 ) . Empathy and enablement scores did not correlate significantly with changes in SF-12 and MYMOP scores at any of the time points . The length of the first consultation was related to initial and subsequent CARE scores , overall enablement , and GHHOS scores at 3 and 12 months . CONCLUSIONS Empathy is crucial for enablement , which , in turn , is strongly related to perceived change in main complaint and well-being . The length of time the clinician spends with a patient at initial consultation appears to be an important factor in these complex relationships among process and outcome BACKGROUND AND OBJECTIVES Since the 1990s , as many women as men have been entering and graduating from medical schools in Western countries . Up to date , prospect i ve studies of physicians ' career paths are lacking . This paper presents the data of the first assessment of a longitudinal survey of a cohort of Swiss medical school graduates , evaluated with regard to how gender and personality traits contribute to their academic achievement and further career planning . METHODS In 2001 , 719 graduate students ( 52.9 % females , 47.1 % males ) returned a postal question naire comprising sections on personality traits , career motivation , and career planning . RESULTS Female graduates scored higher on traits such as helpfulness , relationship consciousness , empathy , family responsibility , and job security . Male students scored higher on traits such as independence , decisiveness , self-confidence , activity , income , and prestige . Women were further advanced in the writing of their thesis ( p = 0.04 ) , chose different topics ( p < 0.001 ) , and had more often decided in which field they wished to specialise ( p = .02 ) . Women preferred fields with intensive patient contact ( p < 0.01 ) , men tended to specialise more in instrumentally oriented and high-technology medicine ( p < .001 ) . The regression model revealed that , apart from gender ( being female ) , instrumentality and extrinsic career motivation predict advanced academic achievement , whereas self-esteem and intrinsic career motivation influence the choice of speciality . CONCLUSIONS The results indicate that women plan their career more purpose fully than men , and that not only gender but also personality traits and career motivation play an important role in academic achievement and career planning 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 |
2,340 | 23,590,757 | Based on the present systematic review , there is no conclusive evidence supporting an association between Se and hypertension . | OBJECTIVE Se is an antioxidant micronutrient and has been studied for its potential role in CVD prevention .
The purpose of the present study was to conduct a systematic review of the literature on the relationship between Se and hypertension . | W.H.O. and U.S. Dept . of Health and Human Services advocate a fat-modified , fruits and vegetable-enriched diet in conjunction with mode-rate physical activity for fitness and health . The Diet and Moderate Exercise Trial ( DAMET ) is a r and omized and controlled study and has provided scientific proof , possibly for the first time , to the above hypothesis ( based on epidemiologic studies , short clinical trials and experimental studies ) that the new approach can cause modulation of risk factors of coronary heart disease ( CHD ) as well as improve fitness . In the DAMET , 231 group A and 232 group B patients with risk factors of CHD were administered a prudent diet for 4 weeks , group A patients in addition were also given at least 400 g/day of fruits and vegetables that are rich in dietary fibre and antioxidants such as vitamins A , C , E , carotene and copper , selenium and magnesium . Fruits and vegetables were administered in a foods-to-eat approach by asking the patients to eat these foods before meals when they were hungry to allow better nutrient adequacy . After 4 weeks , group A patients also did moderate exercise such as brisk walking and spot running compared to no such advice to group B for another 20 weeks . After a follow-up period of 24 weeks , adding exercise to diet was associated with a significant decrease in blood total cholesterol ( 8.9 % ) and LDL-cholesterol ( 6.7 % ) and triglycerides ( 11.9 % ) and a marked increase in HDL-cholesterol ( 16.5 % ) . Mean blood pressures , fasting blood glucose , body weight , body mass index , waist-to-hip ratio and subcutaneous fat also showed a significant decrease in group A , leading to a significant decrease in 12-year CHD risk . A long-term follow-up may be necessary to demonstrate the role of this new approach in decreasing cardiovascular morbidity and mortality AIMS Western Europeans have low blood levels of selenium ( BSe ) , an antioxidant trace element . In a Flemish population , we investigated the cross-sectional and longitudinal association of blood pressure ( BP ) with BSe . METHODS AND RESULTS We r and omly recruited 710 subjects ( mean age 48.8 years ; 51.8 % women ) . We measured BP and BSe and kept participants in follow-up for BP . At baseline , systolic/diastolic BP averaged ( SD ) 130/77 ( 17.3/9.2 ) mmHg . BSe was 97.0 ( 19.0 ) microg/L. Of 385 participants with normal baseline BP ( < 130 and < 85 mmHg ) , over 5.2 years ( range 3.4 - 8.4 years ) , 139 developed high-normal BP ( 130 - 139/85 - 90 mmHg ) or hypertension ( > or=140/90 mmHg ) . In multivariate-adjusted cross-sectional analyses of men , a 20 microg/L ( approximately 1 SD ) higher BSe was associated with lower BP with effect sizes of 2.2 mmHg systolic ( 95 % CI -0.57 to -5.05 ; P = 0.009 ) and 1.5 mmHg diastolic ( 95 % CI -0.56 to -2.44 ; P = 0.017 ) . In prospect i ve analyses of men , a 20 microg/L higher baseline BSe was associated with a 37 % ( 95 % CI -52 to -17 ; P = 0.001 ) lower risk of developing high-normal BP or hypertension . None of these associations was significant in women . CONCLUSION Deficiency of selenium might be an underestimated risk factor for the development of high BP in European men Background Antioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species ( ROS ) . The present study evaluated the effects of prolonged antioxidant treatment on arterial elasticity , inflammatory and metabolic measures in patients with multiple cardiovascular risk factors . Methods Study participants were r and omly assigned to two groups . Group 1 received oral supplementation with 2 capsules per day of Mid Life Guard , SupHerb , Israel . In each capsule vitamin C ( 500 mg ) vitamin E ( 200 iu ) , co-enzyme Q10 ( 60 mg ) and selenium ( 100 mcg ) , Group 2 received matching placebo(SupHerb ) for 6 months . Patients were evaluated for lipid profile , HbA1C , insulin , C-peptide , hs-CRP , endothelin , aldosterone , plasma renin activity and Homeostasis model assessment -insulin resistance ( HOMA-IR ) . Arterial elasticity was evaluated using pulse wave contour analysis ( HDI CR 2000 , Eagan , Minnesota ) . Results Antioxidant-treated patients exhibited significant increases in large arterial elasticity index ( LAEI ) as well as small arterial elasticity index ( SAEI ) . A significant decline HbA1C and a significant increase in HDL-cholesterol were also observed . In the placebo group , significant changes in LAEI , SAEI or metabolic measures were not observed . Conclusions Antioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors . This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure Blood selenium ( Se ) concentrations and glutathione peroxidase ( GSHPX ) activities were measured in 118 men ( 39 + /- SD 15 yr ) and 112 women ( 42 + /- 16 yr ) r and omly selected from the total respondents ( 1192 ) to health survey in Milton , a low soil-selenium area in Otago . GSHPx activities were marginally lower for men ( 11.9 + /- 3.2 units/g Hb ) than for women ( 12.9 + /- 3.8 units/g Hb ) . Blood , erythrocyte and plasma selenium concentrations were about the same for both sexes and means for all subjects ( 61 + /- 15 ; 73 + /- 19 ; 49 + /- 12 ng Se/ml ) were almost identical with a control group of Otago blood donors . No differences in blood levels could be associated with smoking , use of oral contraceptives , arthritis and /or rheumatism , or anti-hypertensive drugs . No relationship was found for the men or women between any of the parameters of selenium status and any of the parameters of risk factors for cardiovascular disease measured in the health survey : age , Quetelet 's index , total skinfolds , systolic and diastolic pressure , pulse rate , plasma lipids and lipoprotein lipid concentrations . Moreover no relationship was found for the subgroups ( 36 % group ) of men and of women with plasma selenium below 45 ng Se/ml . This study indicates that if selenium is important it does not operate through the risk factors of cardiovascular disease as presently understood This study is aim ed at examining whether essential arterial hypertension ( HTN ) or ACE inhibitors have any effect on erythrocyte selenium (Se)-dependent and Se-non-dependent glutathione peroxidase ( GSH-Px ) and superoxide dismutase ( SOD ) activity . Eleven patients with HTN ( 2 men and 9 women ) and 9 healthy volunteers were included in this study after clinical examination and laboratory investigation . The activities of all three enzymes were determined and then the patients were assigned to receive ACE inhibitor therapy consisting of captopril , 25 to 50 mg daily , or enalapril , 10 to 40 mg daily . After 1 year , the determination of antioxidant enzymes was repeated . Our results showed that the initial values of Se-dependent GSH-Px in patients treated with ACE inhibitors were significantly lower ( 19.60 + /- 3.50 microM NADPH/min(-1)/mgHb(-1 ) ) compared with the controls ( 28.64 + /- 4.93 microM NADPH/min(-1)/mgHb(-1 ) ; p < 0.001 ) , whereas the activity of Se-non-dependent GSH-Px was significantly enhanced ( 13.55 + /- 1.46 microM NADPH/min(-1)/mgHb(-1 ) ; p < 0.001 ) compared with the control group ( 9.44 + /- 0.81 microM NADPH/min(-1)/mgHb(-1 ) ; p < 0.001 ) . ACE inhibitors did not significantly change the activity of Se-dependent GSH-Px or Se-non-dependent GSH-Px . No significant alteration was observed in SOD activity The independent association of serum concentrations of saturated and polyunsaturated fatty acids , apolipoproteins AI and B , selenium and vitamins A and E with the risk of death from coronary artery disease ( CAD ) was studied in 92 persons with no previous myocardial infa rct ion , who died from CAD during a 5-year follow-up , and their 92 1-to-1 matched controls . Case-control pairs came from a r and omly drawn population sample of approximately 12,000 persons aged 30 to 64 years from 2 provinces of eastern Finl and , an area with exceptionally high CAD mortality . Control subjects were matched for sex , age , serum cholesterol , mean arterial pressure , tobacco consumption and history of cardiovascular diseases . The persons who died of CAD had lower serum esterified arachidonic acid concentrations before follow-up than the control subjects ( 41 vs 48 mg/liter , p = 0.05 ) , and this difference was greater for pairs with no chest pain on effort ( 36 vs 50 mg/liter , p less than 0.05 ) . The adjusted risk of CAD death in persons with a serum polyunsaturated to saturated ( P/S ) fatty acid ratio of 0.28 or less ( in the lowest tertile ) was 3.5-fold ( 95 % confidence interval [ CI ] , 1.5 to 8.2 ) compared with those with higher serum P/s ratios in a multivariate logistic model and 5.6-fold ( 95 % CI 1.6 to 19.8 ) for pairs with no chest pain on effort . A low serum apolipoprotein AI concentration ( 1.25 g/liter or less , in the lowest tertile ) was associated with a 2.5-fold ( 95 % CI 1.1 to 5.7 ) adjusted risk of CAD death among the chest pain-free persons . ( ABSTRACT TRUNCATED AT 250 WORDS |
2,341 | 27,666,776 | Both COPD and emphysema seem to increase the risk of developing lung cancer , being this risk higher for smokers with heavier tobacco consumption . | Chronic Obstructive Pulmonary Disease ( COPD ) and emphysema have been described as possible risk factors for lung cancer .
We aim to assess the relationship between COPD , emphysema and the onset of lung cancer . | The contribution of emphysema to lung cancer risk has been recognized , but the effect size needs to be further defined . In this study , 565 primary lung cancer cases were enrolled though a prospect i ve lung cancer cohort at Mayo Clinic , and 450 controls were smokers participating in a lung cancer screening study in the same institution using spiral computed tomography ( CT ) . Cases and controls were frequency matched on age , gender , race , smoking status , and residential region . CT imaging using st and ard protocol at the time of lung cancer diagnosis ( case ) or during the study ( control ) was assessed for emphysema by visual scoring CT analysis as a percentage of lung tissue destroyed . The clinical definition of emphysema was the diagnosis recorded in the medical documentation . Using multiple logistic regression models , emphysema ( ≥5 % on CT ) was found to be associated with a 3.8-fold increased lung cancer risk in Caucasians , with higher risk in subgroups of younger ( < 65 years old , OR = 4.64 ) , heavy smokers ( ≥40 pack-years , OR = 4.46 ) , and small-cell lung cancer ( OR = 5.62 ) . When using > 0 % or ≥10 % emphysema on CT , lung cancer risk was 2.79-fold or 3.33-fold higher than controls . Compared with CT evaluation ( using criterion ≥5 % ) , the sensitivity , specificity , positive and negative predictive values , and the accuracy of the clinical diagnosis for emphysema in controls were 19 % , 98 % , 73 % , 84 % , and 83 % , respectively . These results imply that an accurate evaluation of emphysema could help reliably identify individuals at greater risk of lung cancer among smokers . Cancer Prev Res ; 4(1 ) ; 43–50 . © 2010 AACR Prolonged cigarette smoking causes even more deaths from other diseases than from lung cancer . In developed countries , the absolute age-sex-specific lung cancer rates can be used to indicate the approximate proportions due to tobacco of deaths not only from lung cancer itself but also , indirectly , from vascular disease and from various other categories of disease . Even in the absence of direct information on smoking histories , therefore , national mortality from tobacco can be estimated approximately just from the disease mortality statistics that are available from all major developed countries for about 1985 ( and for 1975 and so , by extrapolation , for 1995 ) . The relation between the absolute excess of lung cancer and the proportional excess of other diseases can only be approximate , and so as not to overestimate the effects of tobacco it has been taken to be only half that suggested by a recent large prospect i ve study of smoking and death among one million Americans . Application of such methods indicates that , in developed countries alone , annual deaths from smoking number about 0.9 million in 1965 , 1.3 million in 1975 , 1.7 million in 1985 , and 2.1 million in 1995 ( and hence about 21 million in the decade 1990 - 99 : 5 - 6 million European Community , 5 - 6 million USA , 5 million former USSR , 3 million Eastern and other Europe , and 2 million elsewhere , [ ie , Australia , Canada , Japan , and New Zeal and ] ) . More than half these deaths will be at 35 - 69 years of age : during the 1990s tobacco will in developed countries cause about 30 % of all deaths at 35 - 69 ( making it the largest single cause of premature death ) plus about 14 % of all at older ages . Those killed at older ages are on average already almost 80 years old , however , and might have died soon anyway , but those killed by tobacco at 35 - 69 lose an average of about 23 years of life . At present just under 20 % of all deaths in developed countries are attributed to tobacco , but this percentage is still rising , suggesting that on current smoking patterns just over 20 % of those now living in developed countries will eventually be killed by tobacco ( ie , about a quarter of a billion , out of a current total population of just under one and a quarter billion ) Chronic obstructive pulmonary disease ( COPD ) is a common comorbid disease in lung cancer , estimated to affect 40–70 % of lung cancer patients , depending on diagnostic criteria . As smoking exposure is found in 85–90 % of those diagnosed with either COPD or lung cancer , coexisting disease could merely reflect a shared smoking exposure . Potential confounding by age , sex and pack-yr smoking history , and /or by the possible effects of lung cancer on spirometry , may result in over-diagnosis of COPD prevalence . In the present study , the prevalence of COPD ( pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2 + criteria ) in patients diagnosed with lung cancer was 50 % compared with 8 % in a r and omly recruited community control group , matched for age , sex and pack-yr smoking exposure ( n = 602 , odds ratio 11.6 ; p<0.0001 ) . In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer ( n = 127 ) , we found a nonsignificant increase in COPD prevalence following diagnosis ( 56–61 % ; p = 0.45 ) . After controlling for important variables , the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers ; this is much greater than previously reported . We conclude that COPD is both a common and important independent risk factor for lung cancer RATIONALE Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions , early detection , or chemoprevention . OBJECTIVE To evaluate whether the presence of emphysema on low-radiation-dose CT ( LDCT ) of the chest is an independent risk factor for lung cancer . METHODS The study used data from a prospect i ve cohort of 1,166 former and current smokers participating in a lung cancer screening study . All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies . The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated . Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age , gender , smoking history , and the presence of airway obstruction on spirometry . RESULTS On univariate analysis , the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years , respectively ( risk ratio [ RR ] , 3.33 ; 95 % confidence interval [ CI ] , 1.41 to 7.85 ) . Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry ( RR , 4.33 ; 95 % CI , 1.04 to 18.16 ) . Multivariate analysis showed that the presence of emphysema ( RR , 2.51 ; 95 % CI , 1.01 to 6.23 ) on LDCT but not airway obstruction ( RR , 2.10 ; 95 % CI , 0.79 to 5.58 ) was associated with increased risk of lung cancer after adjusting for potential cofounders . CONCLUSIONS Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer BACKGROUND COPD is an independent risk factor for lung cancer , especially in patients with mild to moderate disease . OBJECTIVE To determine if performing lung cancer screening in GOLD 1 and 2 COPD patients , results in reduced lung cancer mortality . METHODS This study compared patients with mild to moderate COPD from 2 cohorts matched for age , gender , BMI , FEV1 % , pack-yrs history and smoking status . The screening group ( SG ) had an annual low dose computed tomography ( LDCT ) . The control group ( CG ) was prospect ively followed with usual care . Lung cancer incidence and mortality densities were compared between groups . RESULTS From an initial sample of 410 ( SG ) and 735 ( CG ) patients we were able to match 333 patients from each group . At the same follow-up time lung cancer incidence density was 1.79/100 person-years in the SG and 4.14/100 person-years in the CG ( p = 0.004 ) . The most frequent histological type was adenocarcinoma in both SG and CG ( 65 % and 46 % , respectively ) , followed by squamous cell carcinoma ( 25 % and 37 % , respectively ) . Eighty percent of lung cancers in the SG ( 16/20 ) were diagnosed in stage I , and all of CG cancers ( 35/35 ) were in stage III or IV . Mortality incidence density from lung cancer ( 0.08 vs. 2.48/100 person-years , p < 0.001 ) was lower in the SG . CONCLUSIONS This pilot study in patients with mild to moderate COPD suggests that screening with LDCT detects lung cancer in early stages , and could decrease lung cancer mortality in that high risk group . Appropriately design ed studies should confirm these important findings Breathlessness is a common symptom in patients with primary bronchial carcinoma and is often not well-controlled . Most patients are ex- or current smokers , and therefore are at high risk for co-existing chronic obstructive pulmonary disease ( COPD ) . The incidence of airflow obstruction in patients with bronchial carcinoma , its relation to breathlessness , and response to bronchodilator therapy was examined prospect ively . Fifty-seven consecutive patients attending our outpatient clinic with bronchial carcinoma diagnosed in the preceding 12 months were studied ( 22 female , 35 male , mean age 68.4 years ) . Spirometry was performed and breathlessness rated . Those with airflow obstruction ( FEV1:FVC < 65 % and FEV1 < 70 % predicted ) and who judged themselves to have moderate or severe breathlessness , were offered a trial of bronchodilator therapy . The response to regular inhaled fenoterol and ipratropium bromide by metered dose inhaler ( MDI ) and large volume spacer , and to regular nebulized salbutamol and ipratropium bromide was assessed by home peak flow recordings , spirometry and two subjective scores : ( a ) rating of breathlessness on a simple four-point scale , and ( b ) activity score of the St George 's Respiratory Question naire . There was very strong association between airflow obstruction and breathlessness . Twenty-eight patients ( 49 % ) had airflow obstruction , and we had breathlessness ratings on 26 of these patients of whom 18 ( 69 % ) had rated it as moderate or severe . Only four of the patients with airflow obstruction and breathlessness were using bronchodilator therapy . There was no significant difference in the mean age , time from diagnosis , tumour site , or smoking history between the groups with , and without , airflow obstruction . There was no association between cell type and the presence of airflow obstruction . ( ABSTRACT TRUNCATED AT 250 WORDS Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer ( SCLC ) cases . Cases of SCLC were selected from a prospect i ve , multicenter , hospital-based case – control study performed in Spain . Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer . We collected clinical and epidemiological variables according to the study 's protocol . We included 19 SCLC cases , 18 females ( 94.7 % ) , median age 75 years ( interquartile range ( IQR ) 70–80 years ) . Median residential radon concentration was 195 Bq·m−3 ( IQR 130–229 Bq·m−3 ) . 10 patients had limited disease and nine had extended disease . Median survival was 242 days ( IQR 94–496 days ) ; 1- and 2-year survival were 36.8 % and 17.6 % , respectively . Survival was much higher for individuals with limited disease than for those with extended disease ( median 336 versus 235 days ; 1-year survival 50 % versus 22.2 % and 2-year survival 27 % versus 0 % , respectively ) . Performance status at diagnosis was closely related to survival . SCLC is an infrequent , highly aggressive disease in never-smokers . Survival is poor , even for limited disease . Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma . Residential radon exposure is higher than the action levels recommended by the World Health Organization . Small cell lung cancer in never-smokers has a poor survival and is diagnosed at older ages than other lung cancers OBJECTIVES Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history , but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied . We proposed to assess this risk using a quantitative volumetric CT scan analysis . METHODS Sixty-four cases of lung cancer were identified from a prospect i ve cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial . Each case was matched to six control subjects for age , sex , and smoking history . Quantitative CT scan analysis of emphysema was performed . Spirometric measures were also conducted . Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects . RESULTS Decreased FEV(1 ) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 ( 95 % CI , 1.00 - 1.32 ; P = .046 ) and 1.29 ( 95 % CI , 1.02 - 1.62 ; P = .031 ) , respectively . The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 ( 95 % CI , 0.816 - 1.329 ; P = .743 ) . Additionally , there was no significant association between severe emphysema and lung cancer with OR of 1.57 ( 95 % CI , 0.73 - 3.37 ) . CONCLUSIONS We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer . The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies , radiographic evidence of emphysema quantitation methodology , or absence of any relationship between emphysema and lung cancer risk |
2,342 | 23,807,756 | According to the results , there is no evidence from r and omised controlled trials to indicate any benefit of zinc supplementation with regards to serum zinc level in patients with thalassaemia .
There is mixed evidence on the benefit of using zinc supplementation in people with sickle cell disease . | BACKGROUND Haemoglobinopathies , inherited disorders of haemoglobin synthesis ( thalassaemia ) or structure ( sickle cell disease ) , are responsible for significant morbidity and mortality throughout the world .
The WHO estimates that , globally , 5 % of adults are carriers of a haemoglobin condition , 2.9 % are carriers of thalassaemia and 2.3 % are carriers of sickle cell disease .
Carriers are found worldwide as a result of migration of various ethnic groups to different regions of the world .
Zinc is an easily available supplement and intervention programs have been carried out to prevent deficiency in people with thalassaemia or sickle cell anaemia .
It is important to evaluate the role of zinc supplementation in the treatment of thalassaemia and sickle cell anaemia to reduce deaths due to complications .
OBJECTIVES To assess the effect of zinc supplementation in the treatment of thalassaemia and sickle cell disease . | BACKGROUND Poor growth and delayed maturation in children with sickle cell disease ( SCD ) may be due , in part , to mild zinc deficiency . OBJECTIVE The objective was to determine the effects of zinc supplementation on growth and body composition in children with SCD . DESIGN Forty-two prepubertal children ( 20 girls and 22 boys ) aged 4 - 10 y with SCD-SS were r and omly assigned to receive 10 mg elemental Zn/d in cherry syrup ( zinc group ) or cherry syrup alone ( control group ) . The 2 groups were stratified by sex and initial height status . Dietary intakes were evaluated and anthropometric , high-precision knee-height , and plasma zinc measurements were made at baseline and at 3 , 6 , and 12 mo . Body composition was determined every 6 mo with dual-energy X-ray absorptiometry , and z scores for anthropometric variables were computed from national reference data . Longitudinal-mixed-effects analysis was used to test for differences between the groups over the 12-mo observation period . RESULTS Thirty-eight children completed the study . No significant differences were observed at baseline . After 12 mo , the zinc group had significantly greater mean ( + /- SE ) increases in height ( 0.66 + /- 0.29 cm/y ) , sitting height ( 0.97 + /- 0.40 cm/y ) , knee height ( 3.8 + /- 1.2 mm/y ) , and arm circumference z scores ( 0.27 + /- 0.12 cm/y ) . Height-for-age and weight-for-age z scores decreased significantly by 0.11 + /- 0.04 and 0.13 + /- 0.05 , respectively , in the control group but did not change significantly in the zinc group . CONCLUSIONS Prepubertal children with SCD-SS may have zinc deficiency and may benefit from zinc supplementation to improve linear growth and weight gain Objective There are some reports in which a condition of zinc deficiency and its associated outcomes with a change in concentration of serum copper among the thalassemic patients has been highlighted . The aim of this prospect i ve study was to determine the serum zinc and copper levels in children with beta-thalassemia major . Methods In this cross sectional study all children under 12 years affected by beta thalassemia major ( 40 patients ) were evaluated for serum zinc and copper levels in Qazvin thalassemia center ( Qazvin , Iran ) in 2007 . Serum measurements for zinc and copper were performed by atomic absorption spectrophotometer . Findings The mean concentrations of serum zinc and copper levels were 67.35±20.38 and 152.42±24.17 µg/dl respectively . Twenty-six ( 65 % ) of thalassemic patients had zinc concentration under 70 µg/dl ( hypozincemia ) . None of the thalassemic children had copper deficiency . No significant correlation between serum zinc level with age , weight , height , body mass index , duration of blood transfusion , desferrioxamine dose and ferritin level was observed in thalassemic patients ( P=0.3 ) . Conclusion This study revealed that hypozincemia is common in thalassemic patients , but in contrast , there is no copper deficiency . Further evaluation in this regard is recommended Objective In beta thalassemic patients , tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body . This study was conducted to determine the effect of zinc and vitamin E supplementation on antioxidant status in beta-thalassemic major patients . Methods This double blind r and omized clinical trial was carried out on 120 beta thalassemic patients older than 18 years . Patients were r and omly categorized in four groups . Zinc ( 50mg/day ) and vitamin E ( 400mg/day ) supplements were administered for former and latter group , respectively . In the third group both supplements were administered in similar doses . The fourth ( control ) group received no supplement . The effect of supplementations on serum zinc and vitamin E , superoxide dismutase ( SOD ) , glutathione peroxidase ( GPX ) , total antioxidant capacity ( TAC ) and body mass index ( BMI ) were measured at the beginning and the end of the study . Findings Serum zinc levels in group 1 and 3 were significantly increased ( P<0.007 and P<0.005 , respectively ) . Serum vitamin E levels in group 2 and 3 were also increased significantly ( P<0.001 ) . Mean GPX activity in group1 , 2 and 3 decreased significantly ( P<0.015 , P<0.032 and P<0.029 , respectively ) . Mean SOD activity and TAC did not show significant change after supplementation . BMI had significant increase in all treated groups ( P<0.001 ) . Conclusion Our results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage Zinc deficiency is a common nutritional problem in adult sickle‐cell disease ( SCD ) patients . Hyperzincuria and increased requirement of zinc due to continued hemolysis in SCD are probable bases for zinc deficiency in these patients . Zinc deficiency affects adversely T‐helper1 ( TH1 ) functions and cell mediated immunity and interleukin (IL)‐2 production is decreased in zinc deficient subjects . We hypothesized that zinc supplementation will improve T‐helper1 function and decrease incidence of infections in patients with SCD . We tested this hypothesis in 32 SCD subjects who were divided in three groups ( Grs A , B , and C ) . Grs A ( n = 11 ) and B ( n = 10 ) were zinc deficient based on cellular zinc criteria and Gr C ( n = 11 ) were zinc sufficient . Gr A subjects were observed for 1 year ( baseline ) , following which they received zinc acetate ( 50 to 75 mg of elemental zinc orally daily ) for 3 years . Gr B subjects were observed for 1 year ( baseline ) , following which they received placebo for 1 year and then switched to zinc supplementation ( 50 to 75 mg of elemental zinc orally daily ) for 2 years . Gr C subjects did not receive any intervention inasmuch as they were zinc sufficient . Prolonged zinc supplementation result ed in an increase in lymphocyte and granulocyte zinc ( P = 0.0001 ) , and an increase in interleukin‐2 production ( P = 0.0001 ) , decreased incidence of documented bacteriologically positive infections ( P = 0.0026 ) , decreased number of hospitalizations and decreased number of vaso‐occlusive pain crisis ( P = 0.0001 ) . The predominant pathogens isolated were staphylococci and streptococci involving the respiratory tract and aerobic gram‐negative bacteria , particularly Escherichia coli , involving the urinary tract . Further confirmation of our observations will require prospect i ve studies of zinc supplementation in a larger number of SCD patients . Am . J. Hematol . 61:194–202 , 1999 . © 1999 Wiley‐Liss , The toxicity of oral zinc was investigated in patients hospitalized for chronic leg ulcers . Untoward effects were monitored by reference to clinical tolerance , hematological , hepatic and renal parameters , and serum concentrations of copper and iron . The investigation was conducted by comparing two groups of patients who initially did not differ significantly with regard to ulcer area , hemoglobin , leukocytes , copper , iron and zinc . Both groups had serum zinc concentrations in the lower normal range . One group was treated with 3 daily doses of 220 mg oral zinc sulfate and the other with placebo , and hence , untoward effects of zinc should have become manifest in the zinc-treated group . This was not the case . Therefore , oral zinc appears to be well tolerated clinical ly and does not cause hematological , renal or hepatic toxicity . In view of the increasing interest in and range of indications for zinc , particularly in conditions associated with cellular immunological hyporeactivity , this finding is a prerequisite for the institution of clinical zinc therapy Previously , we have documented primary testicular failure in adult male subjects with sickle cell anemia . We have also reported the occurrence of zinc deficiency and suggested that and rogen deficiency may be related to zinc deficiency in such patients . In this study , we present data with respect to the effect of oral zinc supplementation on serum testosterone levels in adult male patients with sickle cell anemia . An increase in serum testosterone , neutrophil zinc , and neutrophil alkaline phosphatase activity was observed in the zinc‐supplemented group in comparison with the group on placebo . Additionally , body weight increased and serum lactic dehydrogenase activity decreased in response to zinc supplementation . We conclude that and rogen deficiency in adult male subjects with sickle cell anemia is correctable with zinc supplementation and that the determination of neutrophil zinc and alkaline phosphatase activity in the neutrophils may be utilized as good indicators of body zinc status in such subjects Abstract In a controlled trial on the effect of oral zinc sulphate in the healing of sickle-cell leg ulcers , the healing-rate in the treatment group was three times faster than in the placebo group |
2,343 | 24,246,405 | There is some controversy in MCo results , however subjects with stroke tended towards longer MCo in both lower limbs in both the acute and chronic stages , when compared with healthy controls .
A higher level of post-stroke walking ability ( speed ; level of independence ) was correlated with longer thigh MCo in the non-affected limb .
CONCLUSIONS Subjects with stroke commonly present longer MCo during walking , probably in an attempt to improve walking ability . | PURPOSE The aim of this paper was to identify and synthesis e existing evidence on lower limb muscle co-contraction ( MCo ) during walking in subjects with stroke . | BACKGROUND Women have higher rates of knee ligament injury than men . Co-contraction of knee muscles is proposed to be an important mechanism to protect the joint from injuries . HYPOTHESIS Females have lower co-contraction levels when compared to males . STUDY DESIGN Exploratory , cross-sectional design . METHODS Thirty-six men and women equally divided into four groups according to gender and activity level ( sedentary and athletic ) were compared in relation to vastus lateralis and biceps femoris co-contraction before heel strike during level walking and before floor contact during l and ing from a jump . Muscular co-contraction was assessed by surface electromyography . Correlations between co-contraction and ligament laxity , extensor and flexor work , and flexion/extension torque ratio were also analyzed . RESULTS No differences between genders were found in the studied situations ( p0.381 ) . During walking , co-contraction was greater in sedentary women compared to athletic women ( p=0.002 ) . A moderate inverse correlation was found between co-contraction during walking and women extensor ( r=-0.613 ; p=0.007 ) and flexor ( r=-0.575 ; p=0.012 ) work . During l and ing from a jump , no variables correlated to co-contraction in any of the groups tested ( r0.477 ; p0.061 ) . CONCLUSION Co-contraction levels were not different between genders . Results suggest that women compensate strength deficits by means of increasing activation levels , possibly to generate adequate joint stiffness to meet stabilization dem and s. However , this is not evident in a more stressful activity like l and ing from a jump . CLINICAL RELEVANCE This study contributes to a better underst and ing of the factors related to joint protection in females , who are at a greater risk of ligament injuries Background and Purpose — The purpose of this study was to compare treadmill and electromechanical gait trainer therapy in subacute , nonambulatory stroke survivors . The gait trainer was design ed to provide nonambulatory subjects the repetitive practice of a gait-like movement without overexerting therapists . Methods — This was a r and omized , controlled study with a crossover design following an A-B-A versus a B-A-B pattern . A consisted of 2 weeks of gait trainer therapy , and B consisted of 2 weeks of treadmill therapy . Thirty nonambulatory hemiparetic patients , 4 to 12 weeks after stroke , were r and omly assigned to 1 of the 2 groups receiving locomotor therapy every workday for 15 to 20 minutes for 6 weeks . Weekly gait ability ( functional ambulation category [ FAC ] ) , gait velocity , and the required physical assistance during both kinds of locomotor therapy were the primary outcome measures , and other motor functions ( Rivermead motor assessment score ) and ankle spasticity ( modified Ashworth score ) were the secondary outcome measures . Follow-up occurred 6 months later . Results — The groups did not differ at study onset with respect to the clinical characteristics and effector variables . During treatment , the FAC , gait velocity , and Rivermead scores improved in both groups , and ankle spasticity did not change . Median FAC level was 4 ( 3 to 4 ) in group A compared with 3 ( 2 to 3 ) in group B at the end of treatment ( P = 0.018 ) , but the difference at 6-month follow up was not significant . The therapeutic effort was less on the gait trainer , with 1 instead of 2 therapists assisting the patient at study onset . All but seven patients preferred the gait trainer . Conclusions — The newly developed gait trainer was at least as effective as treadmill therapy with partial body weight support while requiring less input from the therapist . Further studies are warranted OBJECTIVE To establish whether functional recovery of gait in patients with post-stroke hemiparesis coincides with changes in the temporal patterning of lower extremity muscle activity and coactivity during treadmill walking . METHODS Electromyographic ( EMG ) data from both legs , maximum walking speed , the amount of swing phase asymmetry and clinical measures were obtained from a group of post-acute patients with hemiparesis , as early as possible after admission in a rehabilitation centre ( mean time post-stroke 35 days ) and 1 , 3 , 6 , and 10 weeks later , while all patients participated in a regular rehabilitation program . EMG data from the first assessment were compared to those obtained from a group of healthy controls to identify abnormalities in the temporal patterning of muscle activity . Within subject comparisons of patient data were made over time to investigate whether functional gait recovery was accompanied by changes in the temporal patterns muscle (co-)activity . RESULTS EMG patterns during the first assessment showed a number of abnormalities on the paretic side , namely abnormally long duration s of activity in biceps femoris ( BF ) during the single support ( SS ) phase and in gastrocnemius medialis ( GM ) during the first double support phase ( DS1 ) . Furthermore , in both legs a prolongation of the activity was seen in the rectus femoris ( RF ) during the SS phase . In addition , the duration of BF-RF coactivation was longer on the paretic side than it was in controls . Over time , the level of ambulatory independence , body mobility , and maximum walking speed increased significantly , indicating that substantial improvements in gait ability occurred . Despite these improvements , duration s of muscle ( co- ) activity and the level of swing phase asymmetry did not change during rehabilitation . More specifically , timing abnormalities in muscle (co-)activity that were found during the first assessment did not change significantly , indicating that these aberrations were not an impediment for functional gait improvements . CONCLUSIONS Normalization of the temporal patterning of gait related muscle activity in the lower extremities is not a prerequisite for functional recovery of gait in patients with post-stroke hemiparesis . Apparently , physiological processes other than improved temporal muscular coordination must be important determinants of the restoration of ambulatory capacity after stroke . SIGNIFICANCE Recovery of walking ability in post-stroke hemiparesis is not necessarily associated with , or dependent on , reorganization in the temporal control of gait related muscle activity . Normalization of the temporal coordination of muscle activity during gait may not be an important clinical goal during post-acute rehabilitation OBJECTIVE The purpose of this study was to compare the kinematics , muscle activation , and force production between Parkinson 's patients and healthy , age-matched participants during sit-to-st and transfers . DESIGN This cross-sectional study employed a 2x2x3 multivariate analysis of variance to test for significant differences between and within groups . BACKGROUND The underlying mechanisms that predispose an individual to lose strength during the clinical progression of Parkinson 's disease have proved to be elusive , especially during performance of functional tasks such as the sit to st and transfer . METHODS Twenty-four men ( mean age : 71.5 years ) categorized as Parkinson 's patients ( n = 13 ) and healthy adults ( n = 11 ) participated in this study . Two force platforms measured antero-posterior and vertical force components as well as peak torque . Muscle activation was measured by a six channel , bilateral electromyography system . A lower-body kinematic assessment was conducted utilizing a high-speed motion analysis system . RESULTS No statistically significant differences were found between groups for the outcome variables measured . However , Parkinson 's patients did exhibit significant within-group bilateral differences for the variables of knee angle at seat-off , peak vertical force and peak torque . CONCLUSION Data from this study reveal that persons with mild to moderate Parkinson 's disease exhibit moderately altered bilateral mechanics when performing a sit to st and transfer compared to their healthy peers . RELEVANCE The inability to produce constant equilateral force when performing functional tasks could be an indicator for the increased propensity of falls or other instabilities in this population OBJECTIVE To compare the gait of hemiparetic subjects walking on a treadmill with various body weight supports and walking on the floor . DESIGN Hemiparetic subjects walked on a treadmill , secured in a harness , with no body weight support and with 15 % and 30 % body weight relief , and walked on a floor . SETTING Kinematic laboratory of a department of rehabilitation . SUBJECTS Eighteen hemiparetic stroke patients . MAIN OUTCOME MEASURES Gait cycle parameters and kinesiologic electromyogram of six muscles of the affected side and of two muscles of the nonaffected side . RESULTS On the treadmill , patients walked more slowly because of a reduced cadence , with a longer single stance period of the paretic limb , more symmetrically , and with a larger hip extension ( multivariate profile analysis , p<.05 ) . The mean functional activities of the gastrocnemius muscle and of the first crest of the erector spinae of the paretic side were smaller on the treadmill ( univariate test , p<.05 ) . Further , the premature activity of the gastrocnemius muscle , indicating spasticity , was less on the treadmill ( univariate test , p<.05 ) ; correspondingly the qualitative muscle pattern analysis revealed less co-contraction between the gastrocnemius and tibialis anterior muscles in 11 of the 18 subjects . CONCLUSIONS Treadmill training with partial body weight support in hemiparetic subjects allows them to practice a favorable gait characterized by a greater stimulus for balance training because of the prolonged single stance period of the affected limb , a higher symmetry , less plantar flexor spasticity , and a more regular activation pattern of the shank muscles as compared with floor walking Information on the dynamic properties ( joint stiffness , viscosity and limb inertia ) of the human knee joint is scarce in the literature , especially for actively contracting knee musculature . A joint driving device was developed to apply small-amplitude r and om perturbations to the human knee at several flexion angles with the subject maintaining various levels of muscle contraction . It was found that joint stiffness and viscosity increased with muscle contraction substantially , while limb inertia was constant . Stiffness produced by the quadriceps was highest at 30 degrees flexion and decreased with increasing or decreasing flexion angle , while knee flexors produced highest stiffness at 90 degree flexion . When knee flexion was < 60 degrees , stiffness produced by the quadriceps was higher than that of the hamstrings and gastrocnemius at the same level of background muscle torque , while knee flexor muscles produced higher stiffnesses than the quadriceps at 90 degree flexion . Similar but less obvious trends were observed for joint viscosity . Passive joint stiffness at full knee extension was significantly higher than in more flexed positions . Surprisingly , as the knee joint musculature changed from relaxed to contracting at 50 % MVC , system damping ratio remained at about 0.2 . This outcome potentially simplifies neuromuscular control of the knee joint . In contrast , the natural undamped frequency increased more than twofold , potentially making the knee joint respond more quickly to the central nervous system comm and s. The approach described here provides us with a potentially valuable tool to quantify in vivo dynamic properties of normal and pathological human knee joints Background . Little is known about whether changes in coordination patterns of muscle activation after stroke are related to functional recovery of walking . Objective . The present study investigated the longitudinal relationship between changes in neuromuscular activation patterns of paretic muscles in hemiplegic gait and improvement in walking ability after stroke . Methods . Thirteen patients diagnosed with a first unilateral ischemic stroke had their recovery of walking measured by the Rivermead Mobility Index , Functional Ambulation Categories , Barthel Index , Trunk Control Test , Motricity Index , and comfortable walking speed . Surface electromyography ( SEMG ) of the erector spinae , gluteus maximus , gluteus medius , rectus femoris , vastus lateralis , semitendinosus , gastrocnemius , and tibialis anterior muscles of both legs was used to quantify coordination patterns in comfortable walking mode . All clinical and electromyography-related measurements were taken at 3 , 6 , 9 , 12 , and 24 weeks poststroke . Timing parameters of the SEMG patterns were calculated , using an objective burst detection algorithm , and analyzed with the measures of functional recovery . Results . All functional measures , except Trunk Control Test , showed statistically significant improvement over time , whereas SEMG patterns did not change significantly over time . Conclusion . The lack of significant change in SEMG patterns over time suggests that functional gait improvements may be more related to compensatory strategies in muscle activation of the unaffected leg and biomechanical changes than by restitution of muscle coordination patterns in the affected leg |
2,344 | 24,407,976 | Results Similar to chronic patients , a high prevalence of high-EE in carers of FEP patients was reported .
High-EE status appears to be independent of the patient ’s illness-related characteristics , but dependent of relatives ’ attributions .
In contrast to chronic patients , low levels of FB and psychological distress among family members of FEP patients were observed indicating that in the early stages of the illness family involvement is not yet associated with significant disruption in their lives .
Studies assessing FB in chronic patients have found a well-established link of FB with patient ’s illness-related factors , but in FEP patients the families ’ appraisal of FB is more closely associated with their coping mechanisms . | Purpose The influential role of family in the outcome of chronic schizophrenia is well documented .
However , there has been relatively little research on the intrafamilial relationships of people experiencing their first episode of psychosis ( FEP ) , a point in time when most of the changes in family dynamics are observed .
The aim of this article is to present a review of the literature focusing on the family environment of FEP patients . | Summary A controlled clinical study on the outcome of family intervention in chronic schizophrenics is being carried out in Athens . All subjects participating in the study reside with their families and attend a vocational rehabilitation unit . Those belonging to families characterized by high “ Expressed Emotion ” ( EE ) are r and omly assigned to either the experimental or the control condition . The former receive family intervention combined with individual treatment , the latter individual treatment alone . 75 subjects have entered the study , and 121 relatives were interviewed with the Camberwell Family Interview . 40 patients ( 53.3 % ) were found to belong to high EE families . The present article presents the results of the baseline assessment . It was found that the EE status of the family was significantly associated with measures of psychopathology and social functioning ( BPRS , GAS , DAS , number of residual symptoms ) . Further analyses revealed that these associations exist only when all key relatives express high EE . The implication s of these findings are discussed Purpose To evaluate the contribution of positive affect in the family environment to relapse in first episode psychosis . Method 65 service users with a first episode of psychosis were recruited into the current study along with their key relatives . Relatives were interviewed and rated using the Expressed Emotion ( EE ) measure of warmth , whilst service users completed question naires about the positive and negative affects that they perceived from the family environment . Associations between these measures and relapse were examined in a one-year prospect i ve design . Results Service users were less likely to relapse within 6 and 12-month follow-up periods when their relatives were rated high on EE warmth , or when they perceived more positive affect from the family . The relationships between service users ’ perceived positive affect and relapse were preserved after controlling for baseline symptoms , substance use and employment status . Service users ’ perceptions of positive affect and EE ratings of warmth appeared to be stronger predictors of relapse outcome than criticism and other EE variables . Conclusions Positive family environments may protect against relapse in first episode psychosis . Psychosocial interventions should aim to foster and maintain positive affect in families during the early stages of illness . Further research is needed to underst and the mechanisms linking positive affect and outcomes for people recovering from psychosis This article explores family burden in relation to relatives ' coping strategies and social networks , as well as in relation to the patients ' severity of positive and negative symptoms . Data on the severity of symptoms ( Positive and Negative Syndrome Scale for Schizophrenia [ PANSS ] ) , social functioning ( Social Functioning Scale [ SFS ] ) , caregivers burden ( Interview on Objective and Subjective Family Burden or Entrevista de Carga Familiar Objetiva y Subjetiva [ ECFOS ] ) , coping skills ( Family Coping Question naire [ FCQ ] ) , and social support ( Social Network Question naire [ SNQ ] ) were gathered from a r and omized sample of 101 Chilean out patients and their primary caregivers , mostly mothers . Low levels of burden were typically found , with the exception of moderate levels on general concerns for the ill relative . A hierarchical regression analysis with four blocks showed that clinical characteristics , such as higher frequency of relapses , more positive symptoms and lower independence-performance , together with lower self-control attributed to the patient , decrease in social interests , and less affective support , predict burden . The results support the relevance of psychoeducational interventions where families ' needs are addressed As part of a controlled study of the effectiveness of a counseling program for family caregivers of patients with schizophrenia , we conducted a comprehensive examination of the process . The particular foci were on themes that arose during sessions , principal therapeutic interventions offered , and caveats for counselors working in the field . The most striking finding was the diverse range of themes , covering personal , coping , family , and social aspects of the caregiving experience . This required a correspondingly broad array of interventions . The implication s are clear : confining counseling for caregivers to such traditional dimensions as education or attempts to reduce emotional expressiveness denies them the opportunity to deal with other equally relevant concerns BACKGROUND Poorly defined cohorts and weak study design s have hampered cross-cultural comparisons of course and outcome in schizophrenia . AIMS To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts . To compare mortality , 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables . METHODS Historic prospect i ve study . St and ardised assessment s of course and outcome . RESULTS About 75 % traced . About 50 % of surviving cases had favourable outcomes , but there was marked heterogeneity across geographic centres . In regression models , early ( 2-year ) course patterns were the strongest predictor of 15-year outcome , but recovery varied by location ; 16 % of early unremitting cases achieved late-phase recovery . CONCLUSIONS A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome . Sociocultural conditions appear to modify long-term course . Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains |
2,345 | 24,602,890 | RESULTS 35 included studies revealed that across all chronic pain conditions , psychological interventions reduced pain symptoms and disability posttreatment .
For headache pain , higher treatment dose led to greater reductions in pain .
No effect of dosage was found for other chronic pain conditions . | OBJECTIVES This systematic review and meta- analysis examined the effects of psychological therapies for management of chronic pain in children . | BACKGROUND The conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available OBJECTIVE : This study was design ed to develop and to test a home-based , guided imagery treatment protocol , using audio and video recordings , that is easy for health care professionals and patients to use , is inexpensive , and is applicable to a wide range of health care setting s. METHODS : Thirty-four children , 6 to 15 years of age , with a physician diagnosis of functional abdominal pain were assigned r and omly to receive 2 months of st and ard medical care with or without home-based , guided imagery treatment . Children who received only st and ard medical care initially received guided imagery treatment after 2 months . Children were monitored for 6 months after completion of guided imagery treatment . RESULTS : All treatment material s were reported to be self-explanatory , enjoyable , and easy to underst and and to use . The compliance rate was 98.5 % . In an intention-to-treat analysis , 63.1 % of children in the guided imagery treatment group were treatment responders , compared with 26.7 % in the st and ard medical care – only group ( P = .03 ; number needed to treat : 3 ) . Per- protocol analysis showed similar results ( 73.3 % vs 28.6 % responders ) . When the children in the st and ard medical care group also received guided imagery treatment , 61.5 % became treatment responders . Treatment effects were maintained for 6 months ( 62.5 % responders ) . CONCLUSION : Guided imagery treatment plus medical care was superior to st and ard medical care only for the treatment of abdominal pain , and treatment effects were sustained over a long period Forty-eight adolescents suffering from recurrent tension headache participated in a controlled trial conducted in a high school setting . During the first treatment phase self-help relaxation training was compared with a waiting-list group . Following this phase a pharmacological regimen consisting of a muscle relaxant ( chlormezanone ) and placebo was superimposed on relaxation therapy in a double-blind crossover design . Each treatment phase encompassed a 5-week period . In addition to the evaluation of headache complaints , psychological distress among students was measured with respect to their experience of somatic complaints , depressive , anxiety and stress symptoms . Although self-help relaxation training significantly decreased the severity and annoyance of adolescents ' headache besides their somatic complaints , the clinical improvement of headache was modest . The addition of chlormezanone did not help those who were nonresponders to self-help relaxation training . Finally , a set of pretreatment variables consisting of baseline headache severity and annoyance , experience of anxiety and daily life stress among adolescents could predict outcome of self-help relaxation therapy A comparison was carried out of the efficacy of psychological and drug treatments for children with migraine . Forty-three children aged between 8 and 16 years ( mean age : 11.3 years ) who suffered from migraine received either progressive relaxation or cephalic vasomotor feedback , both with stress management training , or metoprolol , a beta-blocker . Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks . Relaxation and stress management training reduced the headache index ( frequency x intensity of headache episodes ) , more effectively than metoprolol with cephalic vasomotor feedback and stress management training in between . An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake . When comparing pre- to post-treatment data , children treated with relaxation training improved significantly in headache frequency and intensity , whereas those treated with cephalic vasomotor feedback improved significantly in headache frequency and duration as well as mood . The clinical improvement was stable at an 8-months follow-up This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were r and omly allocated to either cognitive-behavioral family intervention ( CBFI ) or st and ard pediatric care ( SPC ) . Both treatment conditions result ed in significant improvements on measures of pain intensity and pain behavior . However , the children receiving CBFI had a higher rate of complete elimination of pain , lower levels of relapse at 6- and 12-month follow-up , and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC . After controlling for pretreatment levels of pain , children 's active self-coping and mothers ' caregiving strategies were significant independent predictors of pain behavior at posttreatment In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Objectives : We evaluated the efficacy of cognitive-behavioral family intervention in the treatment of crises of pain in children with nonorganic recurrent abdominal pain ( RAP ) and the thresholds of pain for 17 body surface areas in these children . Methods : A r and omized clinical trial was undertaken with 32 children between the ages of 5.1 and 13.9 years with nonorganic RAP . A group of 15 patients , aged 9.9 ± 2.2 years ( 11 girls ) , received st and ard pediatric care and cognitive-behavioral family intervention for treatment of pain crises . The control group of 17 children , aged 8.4 ± 2.0 years ( 11 girls ) , received only st and ard pediatric care . These procedures were undertaken by general pediatricians over 4 monthly sessions . An analog visual scale was used to measure the frequency and intensity of the pain crises per month and a mechanical pressure algometer for the measurement of pain threshold . Results : The median frequency of pain crises per month reported by patients at the 3 monthly cognitive-behavioral family intervention sessions was 15 , 5 , 2 and 2 , respectively . In contrast , the median frequency for pain crises per month reported by the control group was 12 , 8 , 10 and 8 , respectively . The difference between the intervention group and the controls was statistically significant for frequency of pain at the second , third and fourth visits . There was no statistical difference for intensity of pain or for measured pain thresholds between the control and the intervention group . Conclusions : The cognitive-behavioral family intervention reduced the frequency of pain crises of children with nonorganic RAP . This successful intervention was carried out by the intervention of general pediatricians OBJECTIVE Juvenile fibromyalgia syndrome ( FMS ) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence -based treatments . The objective of this multisite , single-blind , r and omized clinical trial was to test whether cognitive-behavioral therapy ( CBT ) was superior to fibromyalgia ( FM ) education in reducing functional disability , pain , and symptoms of depression in juvenile FMS . METHODS Participants were 114 adolescents ( ages 11 - 18 years ) with juvenile FMS . After receiving stable medications for 8 weeks , patients were r and omized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions . Assessment s were conducted at baseline , immediately following the 8-week treatment phase , and at 6-month followup . RESULTS The majority of patients ( 87.7 % ) completed the trial per protocol . Intent-to-treat analyses showed that patients in both groups had significant reductions in functional disability , pain , and symptoms of depression at the end of the study , and CBT was significantly superior to FM education in reducing the primary outcome of functional disability ( mean baseline to end-of-treatment difference between groups 5.39 [ 95 % confidence interval 1.57 , 9.22 ] ) . Reduction in symptoms of depression was clinical ly significant for both groups , with mean scores in the range of normal/nondepressed by the end of the study . Reduction in pain was not clinical ly significant for either group ( < 30 % decrease in pain ) . There were no study -related adverse events . CONCLUSION In this controlled trial , CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS & NA ; Little is known about the epidemiology of pain in children . We studied the prevalence of pain in Dutch children aged from 0 to 18 years in the open population , and the relationship with age , gender and pain parameters . A r and om sample of 1300 children aged 0–3 years was taken from the register of population in Rotterdam , The Netherl and s. In the Rotterdam area , 27 primary schools and 14 secondary schools were selected to obtain a representative sample of 5336 children aged 4–18 years . Depending on the age of the child , a question naire was either mailed to the parents ( 0–3 years ) or distributed at school ( 4–18 years ) . Of 6636 children surveyed , 5424 ( 82 % ) responded ; response rates ranged from 64 to 92 % , depending on the subject age and who completed the question naire . Of the respondents , 54 % had experienced pain within the previous 3 months . Overall , a quarter of the respondents reported chronic pain ( recurrent or continuous pain for more than 3 months ) . The prevalence of chronic pain increased with age , and was significantly higher for girls ( P<0.001 ) . In girls , a marked increase occurred in reporting chronic pain between 12 and 14 years of age . The most common types of pain in children were limb pain , headache and abdominal pain . Half of the respondents who had experienced pain reported to have multiple pain , and one‐third of the chronic pain sufferers experienced frequent and intense pain . These multiple pains and severe pains were more often reported by girls ( P<0.001 ) . The intensity of pain was higher in the case of chronic pain ( P<0.001 ) and multiple pains ( P<0.001 ) , and for chronic pain the intensity was higher for girls ( P<0.001 ) . These findings indicate that chronic pain is a common complaint in childhood and adolescence . In particular , the high prevalence of severe chronic pain and multiple pain in girls aged 12 years and over calls for follow‐up investigations documenting the various bio‐psycho‐social factors related to this pain ABSTRACT Cognitive – behavioral therapy ( CBT ) interventions show promise for decreasing chronic pain in youth . However , the availability of CBT is limited by many factors including distance to major treatment centers and expense . This study evaluates a more accessible treatment approach for chronic pediatric pain using an Internet‐delivered family CBT intervention . Participants included 48 children , aged 11–17 years , with chronic headache , abdominal , or musculoskeletal pain and associated functional disability , and their parents . Children were r and omly assigned to a wait‐list control group or an Internet treatment group . Primary treatment outcomes were pain intensity ratings ( 0–10 NRS ) and activity limitations on the Child Activity Limitations Interview , both completed via an online daily diary . In addition to their medical care , the Internet treatment group completed 8 weeks of online modules including relaxation training , cognitive strategies , parent operant techniques , communication strategies , and sleep and activity interventions . Youth r and omized to the wait‐list control group continued with the current medical care only . Findings demonstrated significantly greater reduction in activity limitations and pain intensity at post‐treatment for the Internet treatment group and these effects were maintained at the three‐month follow‐up . Rate of clinical ly significant improvement in pain was also greater for the Internet treatment group than for the wait‐list control group . There were no significant group differences in parental protectiveness or child depressive symptoms post‐treatment . Internet treatment was rated as acceptable by all children and parents . Findings support the efficacy and acceptability of Internet delivery of family CBT for reducing pain and improving function among children and adolescents with chronic pain UNLABELLED The current study examined the Fear Avoidance ( FA ) model of chronic pain in pediatric chronic pain patients . Multiple structural equation models were tested in the current study with pairwise parameter comparisons made between younger children ( 8 - 12 years ) and adolescents ( 13 - 17 years ) . Within a sample of 350 children and adolescents , we examined functional disability and depressive symptoms in separate models with the following predictor variables-pain , pain catastrophizing , fear of pain , and avoidance of activities-after controlling for duration of pain . For a subset of patients ( n = 151 ) , we also tested a brief prospect i ve outcome model with baseline predictor variables and functional disability at 1-month follow-up . The FA models predicting functional disability concurrently and prospect ively were an excellent fit to the data . The theorized FA model for depression was a poor fit . When the model was modified to include direct pathways from the cognitive processes of pain catastrophizing and fear of pain to depressive symptoms , the model fit was significantly improved . In the examination of developmental differences between younger children and adolescent patients , duration of pain contributed to the model for younger children , whereas pain-related fears were more influential for adolescent patients . PERSPECTIVE The FA model of chronic pain appears to be applicable for pediatric patients with some modification to account for developmental differences across childhood . We discuss the developmental , theoretical , and clinical implication s of these results OBJECTIVE AND DESIGN Using a r and omized design with a waiting list control condition , we assessed the effectiveness of an abbreviated cognitive therapy group program for headaches in children 7 to 12 years of age . In the treatment condition , small groups of five to eight children were taught relaxation , distraction , visualization , and stress management skills in two 90-minute sessions . Parent groups , seen concurrently , review ed the children 's program and addressed parenting strategies . The waiting list control groups were treated 5 weeks later . Thirty-six children meeting inclusion criteria were included in the study ; complete data were available for 29 participants ( mean age , 9.4 years ; 66 % female ) . DEPENDENT MEASURES We obtained children 's ratings of headache frequency , intensity , duration , and five other variables in a diary kept for 3 weeks before and 3 weeks after treatment . Parent measures were collected once before treatment and once at 3-month follow-up . RESULTS CHILD RATINGS : The control condition showed a significant reduction in children 's self-rated headache frequency , while the treatment condition did not . On all other self-reported variables , there were no significant differences between the control and treatment conditions . Two participants in each condition achieved a 50 % or greater reduction in a self-rating headache index . RESULTS PARENT RATINGS : Follow-up ratings , obtained over the telephone from parents after the children in both conditions had been treated , indicated that the children in both conditions had experienced reduced intensity , frequency , and duration of headaches and that 82 % of the children were using the techniques taught in the program . Fourteen children achieved a 50 % or greater reduction in a headache index based on parent ratings . CONCLUSIONS Although parents were very positive about the effectiveness of the program , the results for children 's self-ratings do not support the use of this highly abbreviated treatment method Compared the efficacy of a school-based , nurse-administered relaxation training intervention to a no-treatment control condition for children ( 10 - 15 years old ) with chronic tension-type headache and the outcome at posttreatment and a 6-month follow-up . The study was conducted in a controlled between-group design including 26 schoolchildren who were r and omly assigned to the two treatment conditions . Results showed that headache activity in the children treated with relaxation training was significantly more reduced than among those in the no-treatment control group at posttreatment as well as the 6-month follow-up . At these evaluations , 69 % and 73 % of the pupils , respectively , treated with relaxation had achieved a clinical ly significant headache improvement ( at least a 50 % improvement ) as compared to 8 % and 27 % of the pupils , respectively , in the no-treatment control group . Thus , a school-based , nurse-administered relaxation training program seems to be a viable treatment approach for children with chronic tension-type headaches In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Objective . To determine the feasibility of a 12-week Internet-based self-management program of disease-specific information , self-management strategies , and social support with telephone support for youth with juvenile idiopathic arthritis ( JIA ) and their parents , aim ed at reducing physical and emotional symptoms and improving health-related quality of life ( HRQOL ) . Methods . A nonblind pilot r and omized controlled trial ( NCT01011179 ) was conducted to test the feasibility of the “ Teens Taking Charge : Managing Arthritis Online ” Internet intervention across 4 tertiary-level centers in Canada . Participants were 46 adolescents with JIA , ages 12 to 18 years , and 1 parent for each participant , who were r and omized to the control arm ( n = 24 ) or the Internet intervention ( n = 22 ) . Results . The 2 groups were comparable on demographic and disease-related variables and treatment expectation at baseline . Attrition rates were 18.1 % and 20.8 % , respectively , from experimental and control groups . Ninety-one percent of participants r and omized to the experimental group completed all 12 online modules and weekly phone calls with a coach in an average of 14.7 weeks ( SD 2.1 ) . The control group completed 90 % of weekly attention-control phone calls . The Internet treatment was rated as acceptable by all youth and their parents . In posttreatment the experimental group had significantly higher knowledge ( p < 0.001 , effect size 1.32 ) and lower average weekly pain intensity ( p = 0.03 , effect size 0.78 ) . There were no significant group differences in HRQOL , self-efficacy , adherence , and stress posttreatment . Conclusion . Findings support the feasibility ( acceptability , compliance , and user satisfaction ) and initial efficacy of Internet delivery of a self-management program for improving disease-specific knowledge and reducing pain in youth with JIA OBJECTIVES To empirically evaluate a minimal therapist contact CD-ROM pain management program for recurrent pediatric headache developed as part of this study . METHODS Participants were 37 children aged 7 - 12 attending a pediatric neurology clinic for evaluation of recurrent headache . Children who were r and omly assigned to the treatment group worked through the CD-ROM program on home computers for 4 weeks following baseline assessment , whereas those assigned to the wait-list group continued following the prescriptions of their neurologist . Data on daily headache activity and headache-related disability were collected at baseline and up to 3 months after treatment . RESULTS Children who received the adjunctive CD-ROM program had significant improvements in headache activity above and beyond those in the control group . Results provide initial support for the utility of adding an adjunctive CD-ROM psychological intervention to st and ard medical care for recurrent pediatric headache and potentially other chronic pain conditions in children Using a controlled group outcome design , skin temperature biofeedback with autogenic training and autogenic training only was compared to a waiting list as a treatment for childhood headache . Thirty children with migraine headaches , ages 7 to 18 years were r and omly assigned to one of the three conditions . Statistical analyses of headache activity indicated that children in the treatment groups improved in headache frequency and duration but not intensity as compared to the waiting list control group . These findings were consistent through a 6 month follow-up . In terms of clinical improvement , 80 % of the biofeedback group , 50 % of the autogenics group , and none of the waiting list control group were symptom-free . These findings were discussed in relation to past childhood headache studies and implication s for current treatment of children with headaches OBJECTIVE To determine whether a brief intervention for children with functional abdominal pain and their parents ' responses to their child 's pain result ed in improved coping 12 months later . DESIGN Prospect i ve , r and omized , longitudinal study . SETTING Families were recruited during a 4-year period in Seattle , Washington , and Morristown , New Jersey . PARTICIPANTS Two hundred children with persistent functional abdominal pain and their parents . INTERVENTIONS A 3-session social learning and cognitive behavioral therapy intervention or an education and support intervention . MAIN OUTCOME MEASURES Child symptoms and pain-coping responses were monitored using st and ard instruments , as was parental response to child pain behavior . Data were collected at baseline and after treatment ( 1 week and 3 , 6 , and 12 months after treatment ) . This article reports the 12-month data . RESULTS Relative to children in the education and support group , children in the social learning and cognitive behavioral therapy group reported greater baseline to 12-month follow-up decreases in gastrointestinal symptom severity ( estimated mean difference , -0.36 ; 95 % CI , -0.63 to -0.01 ) and greater improvements in pain-coping responses ( estimated mean difference , 0.61 ; 95 % CI , 0.26 to 1.02 ) . Relative to parents in the education and support group , parents in the social learning and cognitive behavioral therapy group reported greater baseline to 12-month decreases in solicitous responses to their child 's symptoms ( estimated mean difference , -0.22 ; 95 % CI , -0.42 to -0.03 ) and greater decreases in maladaptive beliefs regarding their child 's pain ( estimated mean difference , -0.36 ; 95 % CI , -0.59 to -0.13 ) . CONCLUSIONS Results suggest long-term efficacy of a brief intervention to reduce parental solicitousness and increase coping skills . This strategy may be a viable alternative for children with functional abdominal pain . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00494260 OBJECTIVE To investigate whether the combination of st and ard medical care ( SMC ) and short-term cognitive-behavioral family treatment ( CBT ) in the treatment of recurrent abdominal pain ( RAP ) was more effective than SMC alone . METHODS Children recently diagnosed with RAP via physician examination were r and omized into SMC ( n = 29 ) and SMC plus CBT ( n = 40 ) groups . Outcome measures included multiple dimensions of child and parent reported child pain , somatization , and functional disability , and school absences and physician contacts . RESULTS Children and parents participating in the combined SMC + CBT intervention reported significantly less child and parent reported child abdominal pain than children in the SMC intervention immediately following the intervention and up to 1 year following study entry , as well as significantly fewer school absences . Significant differences in functional disability and somatization were not revealed . CONCLUSIONS These results , in combination with previous studies , add support to the effectiveness of CBT intervention in reducing the sensory aspects of RAP . Results are discussed with respect to the cost-benefit of integrated medical and short-term psychological services OBJECTIVE To evaluate the efficacy of a distance treatment delivered through Internet and telephone for pediatric recurrent pain . METHODS Forty-seven participants ( 9 - 16 years of age ) were r and omly assigned to either an Internet-based treatment or a st and ard medical care waitlist . Treatment employed a Web-based manual for children and parents with weekly therapist contact by telephone or e-mail . At 1- and 3-month follow-ups , participants were assessed on the outcome variables of pain and quality of life . A 50 % reduction in diary pain scores was considered clinical ly significant . RESULTS Significant between-group differences were found : 71 and 72 % of the treatment group achieved clinical ly significant improvement at the 1- and 3-month follow-ups , respectively , whereas only 19 and 14 % of the control group achieved the criterion . No significant differences were found on the quality of life variable . CONCLUSIONS Distance methods have considerable potential for making effective treatments more accessible with lower associated costs OBJECTIVES : Unexplained abdominal pain in children has been shown to be related to parental responses to symptoms . This r and omized controlled trial tested the efficacy of an intervention design ed to improve outcomes in idiopathic childhood abdominal pain by altering parental responses to pain and children 's ways of coping and thinking about their symptoms . METHODS : Two hundred children with persistent functional abdominal pain and their parents were r and omly assigned to one of two conditions — a three-session intervention of cognitive-behavioral treatment targeting parents ' responses to their children 's pain complaints and children 's coping responses , or a three-session educational intervention that controlled for time and attention . Parents and children were assessed at pretreatment , and 1 week , 3 months , and 6 months post-treatment . Outcome measures were child and parent reports of child pain levels , function , and adjustment . Process measures included parental protective responses to children 's symptom reports and child coping methods . RESULTS : Children in the cognitive-behavioral condition showed greater baseline to follow-up decreases in pain and gastrointestinal symptom severity ( as reported by parents ) than children in the comparison condition ( time × treatment interaction , P<0.01 ) . Also , parents in the cognitive-behavioral condition reported greater decreases in solicitous responses to their child 's symptoms compared with parents in the comparison condition ( time × treatment interaction , P<0.0001 ) . CONCLUSIONS : An intervention aim ed at reducing protective parental responses and increasing child coping skills is effective in reducing children 's pain and symptom levels compared with an educational control condition OBJECTIVE There are currently no controlled studies of behavioral interventions for juvenile primary fibromyalgia syndrome ( JPFM ) . In this small- sample r and omized study , we tested the efficacy of a behavioral intervention , i.e. , coping skills training ( CST ) , for the treatment of adolescents with JPFM . Outcomes tested in this study were functional disability , pain intensity , pain-coping efficacy , and depressive symptoms . METHODS Thirty patients with JPFM were r and omly assigned to 8 weeks of either CST or self-monitoring . Adolescents in the CST condition received training in active pain-coping techniques , while those in the self-monitoring condition monitored daily pain intensity and sleep quality with no instructions about behavior change . After posttreatment assessment , subjects were crossed over into the opposite treatment arm for 8 weeks ( so that all adolescents eventually received both CST and self-monitoring ) and were reassessed at Week 16 . RESULTS At Week 8 , adolescents in both conditions showed significant decrease in depressive symptoms and functional disability . Those who received CST showed significantly greater ability to cope with pain than those in the self-monitoring condition and a trend toward decreased pain intensity . At Week 16 , adolescents had significantly lower levels of disability and depressive symptoms compared to baseline , but those who received self-monitoring followed by CST seemed to receive the most benefit . CONCLUSION CST can lead to improved functioning among JPFM patients . Although some of the improvement may be due to increased monitoring and attention , CST provides the specific benefit of improving adolescents ' ability to cope with pain OBJECTIVE To evaluate the effectiveness of h and warming biofeedback ( HWB ) and stress management training in comparison to attention ( h and cooling , HCB ) and wait-list control groups . Thermal biofeedback has been used in many pediatric migraine treatment studies and has demonstrated a consistent therapeutic effect . No published studies to date have compared this treatment modality with credible attention control using biofeedback technology . METHODS Thirty-six children and adolescents ( mean age : 12.8 years ) , as well as the mothers and fathers of these children enrolled in the study , were r and omly assigned to the three groups . Thirty-four children completed treatment . Both treatment groups received four sessions of biofeedback training and a portable biofeedback device for home practice . Ratings of treatment credibility showed that the children rated the two treatments as equally credible . Assessment included anxiety and depression question naires for the children and both of their parents . RESULTS Children who had been assigned to the HWB group were more likely to achieve clinical improvement in migraine after treatment than the children in the HCB group . Treatment gains were maintained up to 6 months after treatment . Home practice data reflected a general increase in temperature in the HWB group and a decrease in temperature for the HCB group . CONCLUSIONS The results of this study confirm the findings of earlier pediatric migraine biofeedback treatment studies and also provide support for the specific effect of treatments including stress management and HWB . Future studies with larger sample sizes will aid in delineating the appropriateness of HCB as a control treatment ABSTRACT Although several studies have illustrated the effectiveness of cognitive behavior therapy ( CBT ) on adult pain patients , there are few r and omized controlled trials on children and adolescents . There is particularly a need for studies on pediatric patients who are severely disabled by longst and ing pain syndromes . Acceptance and Commitment Therapy , as an extension of traditional CBT , focuses on improving functioning and quality of life by increasing the patient ’s ability to act effectively in concordance with personal values also in the presence of pain and distress . Following a pilot study , we sought to evaluate the effectiveness of an ACT‐oriented intervention based on exposure and acceptance strategies and to compare this with a multidisciplinary treatment approach including amitriptyline ( n = 32 ) . The ACT condition underwent a relatively brief treatment protocol of approximately 10 weekly sessions . Assessment s were made before and immediately after treatment , as well as at 3.5 and 6.5 months follow‐up . Prolonged treatment in the MDT group complicated comparisons between groups at follow‐up assessment s. Results showed substantial and sustained improvements for the ACT group . When follow‐up assessment s were included , ACT performed significantly better than MDT on perceived functional ability in relation to pain , pain intensity and to pain‐related discomfort ( intent‐to‐treat analyses ) . At post‐treatment , significant differences in favor of the ACT condition were also seen in fear of re/injury or kinesiophobia , pain interference and in quality of life . Thus , results from the present study support previous findings and suggest the effectiveness of this ACT‐oriented intervention for pediatric longst and ing pain syndromes This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence This study compared the relative efficacy of a therapist-assisted relaxation treatment programme with a self-help approach and a self-monitoring condition in the treatment of chronic headaches in adolescents within a school setting . The subjects were 46 high school students , 16 - 18 years of age , who were r and omly assigned to the three treatment conditions . The results indicated that the self-help approach was as effective as the therapist-assisted relaxation condition in reducing the students ' headache , and that these findings were maintained at a 5-month follow-up evaluation . The results suggest that the self-help relaxation procedure is a potential low-cost alternative treatment to a more traditional therapist-based intervention condition The effect of teacher-presented Progressive Relaxation Training ( PRT ) on headaches , fear of failure and school problems was studied in school students . During ten physical education lessons , students received either PRT ( n = 110 ) or placebo training ( n = 92 ) . The effect of the training was investigated in students who indicated the presence of headaches in a pre-training diary . No significant differences were found between both training groups regarding headache frequency , duration and intensity and the psychological variables . On the basis of these and previous findings , it is recommended to present PRT to fairly small groups of self-selected subjects instead of complete classes UNLABELLED A recent r and omized multisite clinical trial found that cognitive-behavioral therapy ( CBT ) was significantly more effective than fibromyalgia education ( FE ) in reducing functional disability in adolescents with juvenile fibromyalgia ( JFM ) . The primary objective of this study was to examine the psychological processes of CBT effectiveness by evaluating changes in pain coping , catastrophizing , and coping efficacy and to test these changes as mediators of continued improvements in functional disability and depressive symptoms at 6-month follow-up . One hundred adolescents ( 11 - 18 years old ) with JFM completed the clinical trial . Coping , catastrophizing , and coping efficacy ( Pain Coping Question naire ) and the outcomes of functional disability ( Functional Disability Inventory ) and depressive symptoms ( Children 's Depression Inventory ) were measured at baseline , posttreatment , and 6-month follow-up . Participants in both conditions showed significant improvement in coping , catastrophizing , and efficacy by the end of the study , but significantly greater improvements were found immediately following treatment for those who received CBT . Treatment gains were maintained at follow-up . Baseline to posttreatment changes in coping , catastrophizing , and efficacy were not found to mediate improvements in functional disability or depressive symptoms from posttreatment to follow-up . Future directions for underst and ing mechanisms of CBT effectiveness in adolescents with chronic pain are discussed . PERSPECTIVE CBT led to significant improvements in pain coping , catastrophizing , and efficacy that were sustained over time in adolescents with juvenile fibromyalgia . Clinicians treating adolescents with JFM should focus on teaching a variety of adaptive coping strategies to help patients simultaneously regain functioning and improve mood A r and omized controlled trial was used to evaluate the effectiveness of relaxation training in the treatment of paediatric migraine . Relaxation training was compared with-two control groups ( psychological placebo and ' own best efforts ' ) in a total of 99 children and adolescents with frequent migraine . Daily recording of the headaches following treatment , three months after treatment and at the one-year follow-up indicated that all three treatments were equally effective . The importance of the use of adequate control conditions which generate equivalent expectancies in pain treatment research was confirmed Tension-type headache is common in children and adolescents and is generally treated with medication , but emerging literature suggests that various behavioral treatments may provide efficacious alternatives to medication . Juvenile tension-type headache sufferers were r and omly assigned to biofeedback-assisted relaxation or relaxation placebo and followed for 1 year . Following treatment , both conditions led to sizeable headache reductions ( approximately 50 % ) . Over time , children receiving biofeedback-assisted relaxation continued to improve and were superior to the control condition at a 6- and 12-month follow-up ( 86 % versus 50 % ) . Biofeedback-assisted relaxation appears to be an efficacious and durable treatment for juvenile tension-type headache and merits further exploration & NA ; The present study compared the efficacy of two active treatments , relaxation training and cognitive coping , with a non‐specific placebo control in the treatment of 42 children and adolescents with migraine . The first treatment is a simplified version of progressive deep muscle relaxation ; the second , a form of cognitive restructuring involving the alteration of dysfunctional thought processes . The results demonstrated that each active treatment was superior to the non‐specific intervention in reducing overall headache activity and frequency but not duration or intensity . There were no differences between the experimental groups , and both continued to improve through a 16‐week follow‐up period , but the control group did not . Initial level of headache severity was an important factor in treatment outcome , with children with severe headaches responding better than those with milder headaches . Possible reasons for the differential treatment effects are discussed , and the implication s for future research are considered OBJECTIVE The efficacy of cognitive-behavioral training in a therapist-administered group format ( TG ) and a self-help format ( SH ) for children with recurrent headache was compared . METHODS A total of 77 children ( 10 - 14 years ) were r and omly assigned to TG ( n=29 ) , SH ( n=27 ) and a waiting-list control group ( WC ; n=19 ) . TG consisted of eight 90-min sessions with groups of five children . SH was conducted via a written manual in which instructions were given and homework tasks were assigned . In both training formats , the topics covered were identical ( e.g. , self-monitoring of headache , trigger analysis , relaxation , etc . ) . Main outcome variables related to changes in headache intensity , duration and frequency as assessed with a diary prior to and following training , as well as at 6-month follow-up . RESULTS Children reported a high degree of satisfaction with the training . No significant differences between the two conditions were found . Differences between treatment groups and WC were statistically corroborated for two headache variables . In both treatments , headache decreased markedly from posttraining to follow-up , with 68 - 76 % of children reporting clinical ly significant improvement . No differential effects of age , gender or headache diagnosis were found . Changes in self-concept and ability to cope with stress after training point to further positive effects of the intervention . CONCLUSION The efficiency of the two training formats is nearly identical . The group format , because of its better acceptance , is recommended for practical use BACKGROUND Recurrent abdominal pain ( RAP ) affects up to 34 % of the world 's population of children . Medical management has been limited , but behavioral strategies have been shown to be effective . In this study several components of published treatment protocol s were adapted and /or improved and then compared using a pretest-posttest control group design . METHODS Sixty-four children and teenagers ( mean age , 9.75 + /- 2.46 years ) with diagnosed recurrent abdominal pain were r and omly assigned to four groups : 1 ) fiber-only comparison group ; 2 ) fiber and biofeedback-assisted cultivated low arousal ; 3 ) fiber , biofeedback , and cognitive-behavioral interventions ; and 4 ) fiber , biofeedback , cognitive-behavioral , and parental support . Participants were treated over 8 weeks in individual sessions . Biofeedback was supplied using small thermal devices . RESULTS All groups showed improvement in self-reported pain , even the fiber-only comparison group ; however , the active treatment groups showed significantly more improvement before and after than the fiber-only comparison group ( fiber only comparison group pain reduction at 79 % ; fiber and biofeedback at 100 % ; fiber , biofeedback , and cognitive-behavioral at 94 % ; fiber , biofeedback , cognitive-behavioral , and parental support at 93 % ) . CONCLUSIONS This suggests that any of the active treatment protocol s assessed in this investigation work better than established treatments that have been reported in the literature . Because the addition of cognitive and parental support components did not seem to increase treatment effectiveness , it is concluded that increased fiber with biofeedback-assisted cultivated low arousal was effective and efficient as a treatment modality & NA ; Migraine headaches are frequent in adolescents . Although many adolescents are adequately treated palliatively with analgesics , an important subgroup requires prophylactic treatment . Medical treatments for adolescents with frequent severe headaches is often problematic . Prophylactic pharmacological treatments are often shunned by adolescents and their parents because of concern over drug usage . Moreover , propranolol , the most widely used prophylactic drug with adults , is frequently not effective . Psychological interventions are effective but are costly and often not available . A r and omized controlled trial was undertaken to evaluate the efficacy and efficiency of a predominantly self‐administered treatment that could be delivered in a very cost‐efficient format . Eighty seven adolescents ( 63 females and 24 males ) ranging in age from 11 to 18 years were r and omly assigned to receive a self‐administered treatment , the same treatment delivered by a therapist or a control treatment . Self‐administered and clinic treatment were equally effective and superior to the control treatment . However , the self‐administered treatment was substantially more efficient . Both active treatments were durable at 1‐year follow‐up |
2,346 | 25,237,538 | There is currently no strong evidence to support previous conclusions that these types of intervention work for children and adolescents . | Aims and method To systematic ally review the published literature on the effectiveness of classroom-based interventions to tackle the stigma of mental illness in young people , and to identify any consistent elements within successful programmes . | Background With the burden of mental illness estimated to be costing the English economy alone around £ 22.5 billion a year [ 1 ] , coupled with growing evidence that many mental disorders have their origins in adolescence , there is increasing pressure for schools to address the emotional well-being of their students , alongside the stigma and discrimination of mental illness . A number of prior educational interventions have been developed and evaluated for this purpose , but inconsistency of findings , reporting st and ards , and method ologies have led the majority of review ers to conclude that the evidence for the efficacy of these programmes remains inconclusive . Methods / Design A cluster r and omised controlled trial design has been employed to enable a feasibility study of ' SchoolSpace ' , an intervention in 7 UK secondary schools addressing stigma of mental illness , mental health literacy , and promotion of mental health . A central aspect of the intervention involves students in the experimental condition interacting with a young person with lived experience of mental illness , a stigma reducing technique design ed to facilitate students ' engagement in the project . The primary outcome is the level of stigma related to mental illness . Secondary outcomes include mental health literacy , resilience to mental illness , and emotional well-being . Outcomes will be measured pre and post intervention , as well as at 6 month follow-up . Discussion The proposed intervention presents the potential for increased engagement due to its combination of education and contact with a young person with lived experience of mental illness . Contact as a technique to reduce discrimination has been evaluated previously in research with adults , but has been employed in only a minority of research trials investigating the impact on youth . Prior to this study , the effect of contact on mental health literacy , resilience , and emotional well-being has not been evaluated to the authors ' knowledge . If efficacious the intervention could provide a reliable and cost-effective method to reduce stigma in young people , whilst increasing mental health literacy , and emotional well-being . Trial registration IS RCT N : IS RCT Stigmatizing , or discriminatory , perspectives and behaviour , which target individuals on the basis of their mental health , are observed in even the youngest school children . We conducted a systematic review of the published and unpublished , scientific literature concerning the benefits and harms of school-based interventions , which were directed at students 18 years of age or younger to prevent or eliminate such stigmatization . Forty relevant studies were identified , yet only a qualitative synthesis was deemed appropriate . Five limitations within the evidence base constituted barriers to drawing conclusive inferences about the effectiveness and harms of school-based interventions : poor reporting quality , a dearth of r and omized controlled trial evidence , poor methods quality for all research design s , considerable clinical heterogeneity , and inconsistent or null results . Nevertheless , certain suggestive evidence derived both from within and beyond our evidence base has allowed us to recommend the development , implementation and evaluation of a curriculum , which fosters the development of empathy and , in turn , an orientation toward social inclusion and inclusiveness . These effects may be achieved largely by bringing especially but not exclusively the youngest children into direct , structured contact with an infant , and likely only the oldest children and youth into direct contact with individuals experiencing mental health difficulties . The possible value of using educational activities , material s and contents to enhance hypothesized benefits accruing to direct contact also requires investigation . Overall , the curriculum might serve as primary prevention for some students and as secondary prevention for others PURPOSE This study examined the effectiveness of an intervention to reduce explicit and implicit stigma-relevant attitudes toward mental illness and treatment-seeking and behavioural indicators of willingness to seek treatment . METHODS Adolescents were r and omly assigned to the experimental ( education about mental illness and treatment involving psychoeducation and contact ( via DVD ) with an affected individual ) or control intervention ( education about tobacco ) . RESULTS Findings suggest the stigma intervention was effective at reducing explicit but not implicit stigma-relevant attitudes . As hypothesized , participants receiving the experimental intervention reported less explicit stigma toward treatment and greater openness to personally seek treatment if they had also reported prior mental health treatment . CONCLUSIONS AND IMPLICATION S These findings support the potential for a brief educational intervention among adolescents to reduce negative attitudes toward mental health treatment , but raise questions about how to effectively address implicit stigma as well as the importance of translating stigma reduction into behavior changes The purpose of this school-based cluster-r and omized trial was to determine the initial acceptability , feasibility , and efficacy of an existing community-based intervention , In Our Own Voice , in a sample of US adolescent girls aged 13 - 17 years ( n = 156 ) . In Our Own Voice is a knowledge-contact intervention that provides knowledge about mental illness to improve mental health literacy and facilitates intergroup contact with persons with mental illness as a means to reduce mental illness stigma . This longitudinal study was set in two public high schools located in a southern urban community of the U.S. Outcomes included measures of mental illness stigma and mental health literacy . Findings support the acceptability and feasibility of the intervention for adolescents who enrolled in the study . Findings to support the efficacy of In Our Own Voice to reduce stigma and improve mental health literacy are mixed . The intervention did not reduce mental illness stigma or improve mental health literacy at one week follow up . The intervention did not reduce mental illness stigma at 4 and 8 weeks follow up . The intervention did improve mental health literacy at 4 and 8 weeks follow up . Previous studies have assessed the preliminary efficacy In Our Own Voice among young adults ; rarely has In Our Own Voice been investigated longitudinally and with adolescents in the United States . This study provides initial data on the effects of In Our Own Voice for this population and can be used to further adapt the intervention for adolescents BACKGROUND A school mental-health programme has been developed as a component of the community mental-health programme in Rawalpindi , Pakistan . It has the objective of improving the underst and ing of disorders of mental health in the rural community . We aim ed to assess the impact of a school mental-health programme on the awareness of schoolchildren , their parents , friends who were not attending school , and neighbours . METHODS We chose two secondary schools for boys and two for girls that were similar in terms of size , staff-pupil ratio , and drop-out rates . 100 children aged 12 - 16 years ( 25 girls and 25 boys in each of the study and control groups ) , 100 parents ( one for each child ) , 100 friends who did not attend school ( one for each child ) , and 100 neighbours ( one for each child ) were given a 19-item question naire before and after the study group had had a 4-month programme of mental-health education . The maximum score for the question naire was 16 points . FINDINGS Before the school mental-health programme the awareness of mental-health issues was poor ( mean score 5.7 - 7.6 ) in the four groups of participants . In the study group there was a significant improvement in the mean scores after the school programme in the schoolchildren ( mean improvement 7.6 [ 95 % CI 6.7 - 8.5 ] , p<0.01 ) , their parents ( 5.3 [ 4.5 - 6.1 ] , p<0.01 ) , friends ( 5.1 [ 4.1 - 6.1 ] , p<0.01 ) , and neighbours ( 3.4 [ 2.6 - 4.2 ] , p<0.01 ) . In the control group the difference in awareness was significant only in schoolchildren ( 1.5 [ 0.5 - 2.3 ] , p=0.01 ) and their friends ( 0.8 [ 0.3 - 1.3 ] , p<0.01 ) . INTERPRETATION The school programme succeeded in improving awareness of mental health in schoolchildren and the community . The schoolchildren were receptive to the programme , and shared their new underst and ing with family , friends , and neighbours . Mental-health planners who wish to improve community awareness of mental health , particularly in areas with low literacy rates , should consider setting up school mental-health programmes This study evaluated the effectiveness of a cognitive behaviour therapy Internet program ( MoodGYM ) for depressive symptoms , attributional style , self‐esteem and beliefs about depression , and on depression and depression‐vulnerable status in male youth . A total of 78 boys age 15 and 16 years were allocated to either undertake MoodGYM or to st and ard personal development activities . Outcomes were measured before commencement , post‐program and 16 weeks post‐program . There were no significant between‐group differences in change scores pre‐ to post‐ or pre‐ to follow‐up using the intention to treat sample or for participants with post‐ and /or follow‐up data . For boys completing 3 or more modules there were small relative benefits of MoodGYM for depressive symptoms ( Effect Size , ES = 0.34 ) , attributional style ( ES = 0.17 ) and self‐esteem ( ES = 0.16 ) at post‐program , although only the effect for self‐esteem was sustained at follow‐up . Both groups showed improvement in their beliefs about depression at follow‐up , with the control group showing a moderate relative benefit ( ES = 0.40 ) . While the numbers are small , there was a reduction in the risk of being depressed in the MoodGYM group of 9 % at post‐treatment compared with a slightly increased risk for the control group . The risk of being classified as vulnerable to depression reduced by 17 % in the MoodGYM group at post‐treatment compared with no change in risk for the control group . These reductions in risk for the MoodGYM group were not sustained at follow‐up . The limitations of the study highlight several important challenges for MoodGYM and other self‐directed Internet cognitive behaviour therapy programs . These include how to ensure enough of the program is received and that people who could potentially benefit access the program and continue to remain engaged with it , and how to enhance the sustainability of any benefits BACKGROUND This study evaluates the benefits of a self-directed Internet intervention for depression ( MoodGYM ) delivered as a part of the high school curriculum . METHOD One hundred and fifty-seven girls , aged 15 and 16 years , were allocated to undertake either MoodGYM or their usual curriculum . MoodGYM 's impact on depressive symptoms , risk of depression , attributional style , depression literacy and attitudes toward depression was examined using r and om effect regression . RESULTS MoodGYM produced a significantly faster rate of decline in depressive symptoms over the trial period than the control condition . The effect size for MoodGYM was not significant immediately after the intervention ( Cohen 's d=.19 , 95 % CI -.18-.56 ) but was moderate and significant 20 weeks after the intervention ( d=.46 , 95 % CI .10-.82 ) . Girls with high depression scores before intervention showed the strongest benefits on self-reported depression at follow-up ( d=.92 , 95 % CI .10 - 1.38 ) . There were no significant intervention effects on depression status , attributional style , depression literacy , and attitudes . Approximately 70 % of girls in the MoodGYM group completed less than three of its modules and completion of fewer modules was related to high depression score before intervention . CONCLUSIONS The findings suggest that there are benefits from MoodGYM on self-reported depressive symptoms but has low rates of completion highlight problems in ensuring adherence to Internet programs for depression |
2,347 | 25,527,900 | RESULTS The findings together suggested that CBT programmes involving computerised elements were well received by children and their families , and its efficacy was almost as favourable as clinic-based CBT . | AIM To conduct a systematic review and meta- analysis of the literature to assess efficacy of internet-delivered cognitive behavioural therapy ( CBT ) for child anxiety disorder . | BACKGROUND Research has demonstrated the effectiveness of computerized cognitive behaviour therapy ( cCBT ) for depression and anxiety in adults , but there has been little work with children and adolescents . AIMS To describe the development of a cCBT intervention ( Think , Feel , Do ) for young people , and preliminary outcomes and feedback from a pilot r and omized controlled trial . METHOD Twenty participants aged 11 to 16 with depression or anxiety were r and omized to receive cCBT immediately or after a delay . St and ardized measures were used to assess self-reported anxiety , depression , self-esteem and cognitions , as well as parent rated strengths and difficulties . A feedback form was also completed to assess young people 's views of the programme . RESULTS A total of 15 participants completed the pre and post assessment s in the trial , and 17 provided feedback on the intervention . Paired sample s t-tests demonstrated significant improvements on 3 subscales in the control condition , compared to 7 subscales in the cCBT condition . Feedback showed moderate to high satisfaction for participants . CONCLUSIONS This study provides encouraging preliminary results for the effectiveness and acceptability of cCBT with this age group OBJECTIVE To evaluate the efficacy of an Internet-based cognitive-behavioral therapy ( CBT ) approach to the treatment of child anxiety disorders . METHODS Seventy-three children with anxiety disorders , aged 7 - 12 years , and their parents were r and omly assigned to either an Internet-based CBT ( NET ) or wait-list ( WL ) condition . Clinical diagnostic assessment and parent and child question naires were completed before and after treatment . The NET condition was reassessed at 6-month follow-up . RESULTS At posttreatment assessment , children in the NET condition showed small but significantly greater reductions in anxiety symptoms and increases in functioning than WL participants . These improvements were enhanced during the 6-month follow-up period , with 75 % of NET children free of their primary diagnosis . CONCLUSIONS Internet delivery of CBT for child anxiety offers promise as a way of increasing access to treatment for this population . Future research is needed to examine ways to increase treatment compliance and further enhance the impact of treatment Background Guided internet-delivered cognitive behavior therapy ( ICBT ) has been tested in several trials on social anxiety disorder ( SAD ) with moderate to large effects . The aims of this study were threefold . First , to compare the effects of ICBT including online discussion forum with a moderated online discussion forum only . Second , to investigate if knowledge about SAD increased following treatment and third to compare the effects of inexperienced versus experienced therapists on patient outcomes . Methods A total of 204 participants with a primary diagnosis of SAD were included and r and omized to either guided ICBT or the control condition . ICBT consisted of a 9-week treatment program which was guided by either psychology students at MSc level ( n = 6 ) or by licensed psychologists with previous experience of ICBT ( n = 7 ) . A knowledge test dealing with social anxiety was administered before and after treatment . Measures of social anxiety and secondary outcomes dealing with general anxiety , depression , and quality of life were administered before and after treatment . In addition , a 1-year follow-up was conducted on the treated individuals . Results Immediately following treatment , the ICBT group showed superior outcome on the Liebowitz Social Anxiety Scale self-report version with a between group posttreatment Hedges g effect size of g = 0.75 . In addition , significant differences on all the secondary outcomes were observed . Gains were well maintained one year later . Knowledge , as assessed by the knowledge test , increased following treatment with little gain in the control group . Therapist experience did not result in different outcomes , but experienced therapists logged in less frequently compared to the inexperienced therapists , suggesting that they needed less time to support patients . Discussion We conclude that guided ICBT reduce symptoms of SAD , increase knowledge about SAD and that therapist experience does not make a difference apart from the finding that experienced therapist may require less time to guide patients . Trial Registration UMIN.ac.jp OBJECTIVE This study examined the feasibility , acceptability , and effects of Camp Cope-A-Lot ( CCAL ) , a computer-assisted cognitive behavioral therapy ( CBT ) for anxiety in youth . METHOD Children ( 49 ; 33 males ) ages 7 - 13 ( M = 10.1 ± 1.6 ; 83.7 % Caucasian , 14.2 % African American , 2 % Hispanic ) with a principal anxiety disorder were r and omly assigned to ( a ) CCAL , ( b ) individual CBT ( ICBT ) , or ( c ) a computer-assisted education , support , and attention ( CESA ) condition . All therapists were from the community ( school or counseling psychologists , clinical psychologist ) or were PsyD or PhD trainees with no experience or training in CBT for child anxiety . Independent diagnostic interviews and self-report measures were completed at pre- and posttreatment and 3-month follow-up . RESULTS At posttreatment , ICBT or CCAL children showed significantly better gains than CESA children ; 70 % , 81 % , and 19 % , respectively , no longer met criteria for their principal anxiety diagnosis . Gains were maintained at follow-up , with no significant differences between ICBT and CCAL . Parents and children rated all treatments acceptable , with CCAL and ICBT children rating higher satisfaction than CESA children . CONCLUSIONS Findings support the feasibility , acceptability and beneficial effects of CCAL for anxious youth . Discussion considers the potential of computer-assisted treatments in the dissemination of empirically supported treatments BACKGROUND Cognitive Behaviour Therapy self-help has been recommended in the NICE guidelines for the treatment of anxiety and depression . However , little is known about who benefits from self-help and the potential drawbacks and problems of using this approach . AIMS To address the current gap in knowledge , we contacted accredited BABCP practitioners to examine practitioner use and attitudes to self-help , current trends of use , and to identify possible problems with this therapy . METHOD A 50 % r and om sample of all accredited BABCP practitioners was approached , and the overall response rate for the survey was 57.6 % . RESULTS Self-help material s were seen positively by therapists and were used by 99.6 % , mainly as an adjunct to individual therapy . Only 38.2 % had been trained in the use of self-help , with those trained being more likely to recommend self-help . Higher levels of patient motivation , credibility , likely adherence , self-efficacy and a lower degree of hopelessness were the five factors identified by more than 70 % of respondents as predicting successful patient outcome with self-help . Non-compliance and a lack of detection of a worsening of the patient 's clinical state due to reduced therapist contact were viewed as being the most important problems with self-help by more than 70 % of respondents . CONCLUSIONS Preferable patient characteristics for self-help have been identified , as have potential problems and adverse consequences Background Little is known about the factors that influence acceptability of and adherence to online psychological interventions . Evidence is needed to guide further development of promising programs . Objective Our goal was to investigate users ’ views of two online approaches to self-help for depression : computerized cognitive behavior therapy ( cCBT ) and informational websites , in a workplace context . Computerized CBT offers an inexpensive and accessible alternative to face-to-face therapy , and employers have an interest in reducing the working time lost to depression or stress . Yet little is known about how employees , who have actual experience of using online approaches , judge the intervention as a process . Methods The qualitative data reported here were collected within an online r and omized controlled trial whose participants had diagnosable depression . The experimental intervention was a 5-week cCBT program called MoodGYM , and the control condition was five informational websites about mental health . Data were collected via online question naires . There was no evidence of the superiority of either in terms of treatment outcomes . In parallel , using brief rating scales and open-ended questions design ed for this purpose , we examined the relative acceptability of each approach over time , including perceptions of cCBT compared to seeing a health care professional . Results At least 60 % of participants held online therapy to be at least as acceptable as seeing a professional about mental health issues , and they were more likely to retain this opinion over time if they used the interactive program , MoodGYM , rather than informational websites alone . Barriers to cCBT use fell into four categories : intrinsic , intrapersonal problems ; extrinsic technical problems ; generic issues mostly pertaining to perceptions of cCBT ; and specific issues about the intervention or control condition . These indicate strategies for improving engagement . Conclusions As first-aid for mild to moderate mental health problems , evidence -based computerized approaches have broad acceptability . This could be increased by attending to the barriers noted here and by proactively managing users ’ expectations at individual and organizational levels . The findings have implication s for occupational health providers and others addressing the needs of working-age adults with depression . They also raise method ological issues for online research . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 24529487 ; http://www.controlled-trials.com/IS RCT N24529487 ( Archived by Webcite at http://www.webcitation.org/6O8cCL4mh ) Research suggests that the sequelae of childhood anxiety disorders , if left untreated , can include chronic anxiety , depression , and substance abuse . The current study evaluated the maintenance of outcomes of children who received a 16-week cognitive-behavioral treatment for primary anxiety disorders ( generalized , separation , and social anxiety disorders ) an average of 7.4 years earlier . The 86 participants ( ages 15 to 22 years ; 91 % of the original sample ) and their parents completed diagnostic interviews and self- and parent-report measures . According to the diagnostic interviews , a meaningful percentage of participants maintained significant improvements in anxiety at long-term follow-up . With regard to sequelae , positive responders to anxiety treatment , as compared with less positive responders , had a reduced amount of substance use involvement and related problems at long-term follow-up . The findings are discussed with regard to child anxiety and some of its sequelae Seventy-two clinical ly anxious children , aged 7 to 14 years , were r and omly allocated to clinic-based , cognitive-behavior therapy , the same treatment partially delivered via the Internet , or a wait-list control ( WL ) . Children in the clinic and clinic-plus-Internet conditions showed significantly greater reductions in anxiety from pre- to posttreatment and were more likely to be free of their anxiety diagnoses , compared with the WL group . Improvements were maintained at 12-month follow-up for both therapy conditions , with minimal difference in outcomes between interventions . The Internet treatment content was highly acceptable to families , with minimal dropout and a high level of therapy compliance |
2,348 | 21,464,420 | The quality of HRQOL reporting has improved ; both reporting of clinical ly significant differences and statistical testing of HRQOL have improved .
The number of NSCLC RCTs incorporating HRQOL assessment s has considerably increased .
HRQOL continues to demonstrate its importance in RCTs , especially in those studies in which no OS difference is found . | PURPOSE This study is an up date of a systematic review of health-related quality -of-life ( HRQOL ) methodology reporting in non-small-cell lung cancer ( NSCLC ) r and omized controlled trials ( RCTs ) .
The objective was to evaluate HRQOL methodology reporting over the last decade and its benefit for clinical decision making . | PURPOSE Cancers rely on angiogenesis for their growth and dissemination . We hypothesized that thalidomide , an oral antiangiogenic agent , when combined with chemotherapy , and as maintenance treatment , would improve survival in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Seven hundred twenty-two patients were r and omly assigned to receive placebo or thalidomide capsules 100 to 200 mg daily for up to 2 years . All patients received gemcitabine and carboplatin every 3 weeks for up to four cycles . End points were overall survival ( OS ) , progression-free survival ( PFS ) , response rate , grade 3/4 toxicity , and quality of life ( QoL ) . RESULTS The median OS rates were 8.9 months ( placebo ) and 8.5 months ( thalidomide ) . The hazard ratio ( HR ) was 1.13 ( 95 % CI , 0.97 to 1.32 ; P = .12 ) . The 2-year survival rate was 16 % and 12 % in the placebo and thalidomide arms , respectively . The PFS results were consistent with those for OS . The risk of having a thrombotic event was increased by 74 % in the thalidomide group : HR of 1.74 ( 95 % CI , 1.20 to 2.52 ; P = .003 ) . There were no differences in hematologic toxicities , but a slight excess of rash and neuropathy in the thalidomide group . QoL scores were similar but thalidomide was associated with less insomnia , and more constipation and peripheral neuropathy . In a retrospective analysis , patients with nonsquamous histology in the thalidomide group had a poorer survival : 2-year risk difference of 10 % ( 95 % CI , 4 % to 16 % ; P < .001 ) . CONCLUSION In this large trial of patients with NSCLC , thalidomide in combination with chemotherapy did not improve survival overall , but increased the risk of thrombotic events . Unexpectedly , survival was significantly worse in patients with nonsquamous histology We present experience from a phase II r and omized clinical trial , comparing st and ard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer ( NSCLC ) and who are unfit for st and ard platin-based chemotherapy . Eligible patients had microscopically confirmed NSCLC in stage IIIB ( wet ) or IV , were chemo-naive , and were in poor performance status or presented with significant comorbidity . St and ard treatment with gemcitabine , 1250 mg/m2 in 20–30 min on days 1 and 8 as monotherapy ( arm A ) was compared with low-dose gemcitabine in long infusion ( 200 mg/m2 in 6 h on day 1 ) and cisplatin at 60 mg/m2 on day 2 ( arm B ) . Both treatment schedules were repeated every 3 weeks until disease progression , unacceptable toxicity , or to a maximum of six cycles . A total of 112 patients ( 83 male , 29 female , median age 66 years ) were r and omized between arm A ( 57 patients ) and B ( 55 patients ) . The two groups were balanced for prognostic factors . Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response . The median number of cycles was four and five for arms A and B , respectively . Except for grade 3 anemia ( one patient in arm A and two in arm B ) , no other major toxicity was seen . Regarding response to treatment , arm B was superior : 1 complete response and 13 partial remissions ( response rate 26.9 % ) as compared with five partial remissions ( response rate 9.4 % ) in arm A ( P<0.01 ) . The median time to progression was 3.8 and 5.6 months , and the median survival was 4.3 and 6.8 months for arms A and B , respectively ( P<0.05 ) . Treatment with low-dose gemcitabine in long infusion and cisplatin at reduced dose has very low toxicity , is effective , was found to be superior to monotherapy with gemcitabine in st and ard doses , and is suitable for patients with NSCLC who can not tolerate a st and ard platin-based doublet PURPOSE To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with histologically proven NSCLC , performance score < 2 , weight loss < 10 % , and normal organ functions were r and omized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone ( both 60 Gy ) . Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria ( NCI CTC ) and the Radiation Therapy Oncology Group ( RTOG ) criteria . Quality of life was measured with European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30/LC13 question naires . RESULTS One-hundred and sixty patients were included . Pathologically confirmed persistent tumor was present in 53 % of patients in the combination arm versus 58 % in the radiotherapy alone arm ( P=0.5 ) . Median survival in the combination arm was 11.8 [ 95 % confidence interval ( CI ) 9.3 - 14.2 ] months and in the radiotherapy alone arm 11.7 ( 95 % CI 8.1 - 15.5 ) months ; progression-free survival was not different between arms [ 6.8 and 7.5 months , respectively ( P=0.28 ) ] . Acute toxicity was mild , late toxicity was radiation-induced cardiomyopathy ( three patients ) and pulmonary fibrosis ( five patients ) . Quality of life was not different between arms , but in all measured patients cough and dyspnea improved , pain became less , and slight paresthesia developed 3 months after treatment . CONCLUSION Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival BACKGROUND AND PURPOSE To compare the course of symptoms and health-related quality -of-life ( HRQOL ) after immediate thoracic radiotherapy ( TRT ) between symptomatic ( S ) and non-symptomatic ( NS ) patients with advanced NSCLC . PATIENTS AND METHODS 407 stage III/IV patients were initially treated with immediate TRT within a r and omised phase III trial comparing different fractionation schedules . At inclusion , patients were prospect ively stratified according to presence ( S ) or absence ( NS ) of tumour-related chest/airway symptoms to facilitate comparison between these groups . The EORTC QLQ-C30 and LC-13 were used for symptom and HRQOL assessment s at baseline and at regular intervals up to 1 year ( N=395 ) . RESULTS NS patients had significantly more favourable baseline characteristics when compared to S patients with a median survival of 11.8 versus 6.0 months ( P<0.0001 ) , respectively . At baseline , S patients demonstrated HRQOL scores inferior to those of NS patients ( P<0.01 ) for most scales . Until week 14 , NS patients developed more symptoms while S patients experienced symptom relief in most scales . After week 14 , no significant differences could be observed between the groups . CONCLUSION This study indicates that immediate TRT , given to patients with minimal/none chest symptoms , does not prevent development of disease-related symptoms and diminished HRQOL . A wait- and -see policy appears to be acceptable PURPOSE Gemcitabine plus carboplatin ( GC ) is active as front-line treatment for advanced non-small-cell lung cancer ( NSCLC ) . For patients without progression , timing of second-line chemotherapy for optimum clinical benefit remains uncertain . This phase III , r and omized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression . PATIENTS AND METHODS The chemotherapy-naïve patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC . Gemcitabine ( 1,000 mg/m(2 ) ) was administered on days 1 and 8 followed by carboplatin ( area under the curve = 5 ) on day 1 . After four 21-day cycles , patients who did not have progression were r and omly assigned either to an immediate docetaxel group ( docetaxel 75 mg/m(2 ) on day 1 every 21 days , with maximum of six cycles ) or to a delayed docetaxel group . The primary end point was overall survival ( OS ) measured from r and om assignment . Additional analyses included tumor response , toxicity , progression-free survival ( PFS ) , and quality of life ( QOL ) . RESULTS Enrollment totaled 566 patients ; 398 patients completed GC ; 309 patients were r and omly assigned equally to the two docetaxel treatment groups . Toxicity profiles were generally comparable for the docetaxel groups . Median PFS for immediate docetaxel ( 5.7 months ) was significantly greater ( P = .0001 ) than for delayed docetaxel ( 2.7 months ) . Median OS for immediate docetaxel ( 12.3 months ) was greater than for delayed docetaxel ( 9.7 months ) , but the difference was not statistically significant ( P = .0853 ) . QOL results were not statistically different ( P = .76 ) between docetaxel groups . CONCLUSION We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC , without increasing toxicity or decreasing QOL The purpose of our study was to compare progression-free survival and quality of life ( QOL ) after cisplatin – gemcitabine ( CG ) or epirubicin – gemcitabine ( EG ) in chemotherapy-naive patients with unresectable non-small-cell lung cancer . Patients ( n=240 ) were r and omised to receive gemcitabine 1125 mg m−2 ( days 1 and 8) plus either cisplatin 80 mg m−2 ( day 2 ) or epirubicin 100 mg m−2 ( day 1 ) every 3 weeks for a maximum of five cycles . Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status ⩽2 . QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 question naires . There were no significant differences in median progression-free survival ( CG 26 weeks , EG 23 weeks ) , median overall survival ( CG 43 weeks , EG 36 weeks ) , or tumour response rates ( CG 46 % , EG 36 % ) . Toxicity was mainly haematologic . In the EG arm granulocytopenia occurred more frequently , leading to more febrile neutropenia . Also , elevation of serum transaminases , mucositis , fever , and decline in LVEF were more common in the EG arm . In the CG arm , more patients experienced elevated serum creatinine levels , sensory neuropathy , nausea , and vomiting . Global QOL was not different in both arms . Progression-free survival , overall survival , response rate , and QOL were not different between both arms ; however , overall toxicity was more severe in the EG arm Objective : Gemcitabine in low dose in prolonged infusion is a treatment with documented activity against a variety of tumors . We here report the first r and omized trial to compare st and ard brief and low-dose prolonged infusion of gemcitabine . Patients and Methods : Eligible patients had non-small cell lung cancer in stage IIIB ( wet ) or IV , Karnofsky performance status 100 to 70 ( Eastern Cooperative Oncology Group 0–2 ) , measurable disease , were chemonaïve and fulfilled the st and ard criteria for chemotherapy . In arm A ( st and ard treatment ) , gemcitabine was given at 1250 mg/m2 in 20 to 30 minutes and in arm B ( prolonged infusion ) at 250 mg/m2 in 6 hours infusion . All patients received gemcitabine on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles , followed by two cycles of gemcitabine as monotherapy . Results : A total of 249 patients ( 188 men and 61 women , median age 58 years ) were r and omized between arm A ( 125 patients ) and arm B ( 124 patients ) . Adenocarcinoma ( 53.9 % ) was the predominant histologic type ; 92 % of patients were in stage IV . The two groups were balanced for prognostic factors ; however , group A had fewer patients with significant weight loss and no patient with lung cancer as a second malignancy or after radiotherapy for brain metastases . Grade 3 or greater toxicity was rare : anemia in 0.8 and 3.2 % , neutropenia in 21.6 and 22.6 % , thrombocytopenia in 0 and 1.6 % , and nausea/vomiting in 4 and 8.1 % for arms A and B , respectively . Alopecia was seen in 54.5 % of patients in arm B , as compared with 9.7 % in arm A. No patient died of treatment-related toxicity . During cycle 5 , 47.7 % of patients in arm A and 60.7 % in arm B reported improved well-being , as compared with the status before chemotherapy . Patients in arm A had no complete remission , 32.8 % partial responses , 48 % minimal responses or stable disease , 13.6 % progressions , and 5.6 % were not evaluable . For arm B , the corresponding figures are as follows : complete remission 0.8 % , partial responses 46 % ( for overall response rate of 46.8 % ) , minimal responses or stable disease 36.3 % , progression 12.1 % , and not evaluable 4.8 % . Median progression-free survival was 5.5 and 6.0 months , median overall survival was 10.1 and 10.0 months , and 1-year survival was 46.6 and 41.1 % for arms A and B , respectively . For the 71 patients with squamous carcinoma , arm B seems superior to arm A , as seen by the higher overall response rate ( 51.3 versus 35.5 % ) , longer median progression-free survival ( 6.2 versus 4.9 months ) , and longer median survival ( 11.3 versus 8.5 months ) . However , because of the small number of patients , these differences did not reach the level of statistical significance . Conclusion : In the treatment of advanced non-small cell lung cancer , gemcitabine in low dose in prolonged infusion in combination with cisplatin has low toxicity and has activity comparable with gemcitabine in higher dose in st and ard brief infusion . Low-dose gemcitabine may be preferred for incurable cancer among economically deprivileged patients . In addition , apparent superior activity against squamous carcinoma opens new perspectives and deserves further research BACKGROUND The purpose of this study was to compare quality of life and overall toxicity in patients with advanced non-small-cell lung cancer ( NSCLC ) treated with vinorelbine-gemcitabine ( VG ) or carboplatin-paclitaxel ( Taxol ) ( CP ) . PATIENTS AND METHODS A total of 165 previously untreated patients were r and omized to the two regimens . Quality of life was assessed by the Lung Cancer Symptom Scale ( LCSS ) . Overall toxicity and secondary efficacy end points were evaluated by st and ard WHO criteria . RESULTS There was no significant difference in overall quality of life between the two treatments . Neutropenia , thrombocytopenia , peripheral neuropathy , and alopecia , were more common in the CP arm , whereas constipation was more frequent in the VG arm . Response rates were 14.6 % in the VG arm and 16.9 % in the CP arm . Median survival times were 7.8 and 8.6 months , and 1 year survival rates were 38.4 % and 31.9 % , respectively . CONCLUSIONS Patients treated with VG experienced lower toxicity , but overall quality of life was similar in both arms . Efficacy seemed comparable between VG and CP . Our study shows that VG is a viable alternative to platinum-based chemotherapy in patients with advanced NSCLC This r and omised phase III study in advanced non-small cell lung cancer ( NSCLC ) patients was conducted to compare vinorelbine/carboplatin ( VC ) and gemcitabine/carboplatin ( GC ) regarding efficacy , health-related quality of life ( HRQOL ) and toxicity . Chemonaive patients with NSCLC stage IIIB/IV and WHO performance status 0–2 were eligible . No upper age limit was defined . Patients received vinorelbine 25 mg m−2 or gemcitabine 1000 mg m−2 on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles . HRQOL question naires were completed at baseline , before chemotherapy and every 8 weeks until 49 weeks . During 14 months , 432 patients were included ( VC , n=218 ; GC , n=214 ) . Median survival was 7.3 vs 6.4 months , 1-year survival 28 vs 30 % and 2-year survival 7 vs 7 % in the VC and GC arm , respectively ( P=0.89 ) . HRQOL , represented by global QOL , nausea/vomiting , dyspnoea and pain , showed no significant differences . More grade 3–4 anaemia ( P<0.01 ) , thrombocytopenia ( P<0.01 ) and transfusions of blood ( P<0.01 ) or platelets ( P<0.01 ) were observed in the GC arm . There was more grade 3–4 leucopoenia ( P<0.01 ) in the VC arm , but the rate of neutropenic infections was the same ( P=0.87 ) . In conclusion , overall survival and HRQOL are similar , while grade 3–4 toxicity requiring interventions are less frequent when VC is compared to GC in advanced NSCLC PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin ( TC ) as first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This multicenter , open-label , phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB ( pleural effusion ) or IV NSCLC , without restrictions by histology or epidermal growth factor receptor expression . Patients were r and omly assigned to cetuximab/TC or TC . TC consisted of paclitaxel ( 225 mg/m(2 ) ) or docetaxel ( 75 mg/m(2 ) ) , at the investigator 's discretion , and carboplatin ( area under the curve = 6 ) on day 1 every 3 weeks for < or = six cycles ; cetuximab ( 400 mg/m(2 ) on day 1 , 250 mg/m(2 ) weekly ) was administered until progression or unacceptable toxicity . The primary end point was progression-free survival assessed by independent radiologic review committee ( PFS-IRRC ) ; overall response rate ( ORR ) , overall survival ( OS ) , quality of life ( QoL ) , and safety were key secondary end points . PFS and ORR assessed by investigators were also evaluated . Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC ( hazard ratio [ HR ] = 0.902 ; 95 % CI , 0.761 to 1.069 ; P = .236 ) . Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC ( HR = 0.890 ; 95 % CI , 0.754 to 1.051 ; P = .169 ) . ORR-IRRC was 25.7 % with cetuximab/TC versus 17.2 % with TC ( P = .007 ) . The safety profile of this combination was manageable and consistent with its individual components . CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point , PFS-IRRC . There was significant improvement in ORR by IRRC . The difference in OS favored cetuximab but did not reach statistical significance BACKGROUND This open-label , r and omised phase III study was design ed to further investigate the clinical activity and safety of SRL172 ( killed Mycobacterium vaccae suspension ) with chemotherapy in the treatment of non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omised to receive platinum-based chemotherapy , consisting of up to six cycles of MVP ( mitomycin , vinblastine and cisplatin or carboplatin ) with ( 210 patients ) or without ( 209 patients ) monthly SRL172 . RESULTS There was no statistical difference between the two groups in overall survival ( primary efficacy end point ) over the course of the study ( median overall survival of 223 days versus 225 days ; P = 0.65 ) . However , a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group ( 90 % ) , than in the chemotherapy alone group ( 83 % ) ( P = 0.061 ) . At the end of the treatment phase , the response rate was 37 % in the combined group and 33 % in the chemotherapy alone group . Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score ( -14.3 ) than patients in the chemotherapy plus SRL172 group ( -6.6 ) ( P = 0.02 ) . CONCLUSION In this non-placebo controlled trial , SRL172 when added to st and ard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times BACKGROUND Previous work highlighted a number of method ological constraints when reporting health-related quality of life ( HRQOL ) outcomes from r and omized controlled trials ( RCTs ) . Given this , the objective of this study was to investigate whether the quality of such HRQOL reports has improved over time . MATERIAL S AND METHODS On the basis of a predefined set of criteria , 159 RCTs with a HRQOL end point , published between 1990 and 2004 were identified and analyzed . Each study was evaluated by a number of issues ( e.g. sample size and industry sponsorship ) and by the " minimum st and ard checklist for evaluating HRQOL outcomes in cancer clinical trials " . RESULTS The quality of HRQOL reports , as measured by the overall checklist score , was independently related to more recently published studies ( P < 0.0001 ) . This relationship was independent of industry funded , HRQOL end point ( primary versus secondary ) , cancer disease site , size of the study and HRQOL difference between treatment arms . While only 39.3 % of studies published between 1990 and 2000 ( 89/159 RCTs ) were identified as being probably robust , thus likely to support clinical decision making , this percentage was 64.3 % for studies published after 2000 ( 70/159 RCTs ) . CONCLUSION Since we found a significant learning curve in HRQOL trial reporting since 1990 , it can be expected that HRQOL data will increasingly impact on clinical decision making and treatment policies in the near future BACKGROUND The modest improvement in median survival of advanced non-small-cell lung cancer ( NSCLC ) by cisplatin-based chemotherapy has led to the current opinion that clinical benefit for the patient is at least as important an end-point as objective response rate ( ORR ) or survival . Clinical benefit response was the primary end-point of this prospect i ve r and omised trial in symptomatic , advanced stage IIIB/IV NSCLC , comparing single agent gemcitabine ( GEM ) to cisplatin-based chemotherapy . PATIENTS AND METHODS Patients received either GEM ( 1000 mg/m2 , days 1 , 8 and 15 ) or cisplatin ( 100 mg/M2 , day 1 ) plus Vindesine ( 3 mg/m2 , days 1 and 15 ) ( PV ) , both every four weeks . Clinical benefit was measured by a simple metric based on changes in a visual analogue symptom score list , the Karnofsky performance status and the weight . RESULTS One hundred sixty-nine patients were r and omised ( 84 GEM , 85 PV ) . Prognostic factors and baseline symptoms were well balanced between the two arms . Most of the the objective responders and about half of the patients with disease stabilisation experienced clinical benefit . Compared to PV , a significantly larger number of GEM-treated patients experienced a clinical benefit ( 48.1 vs. 28.9 % , P = 0.03 ) that lasted significantly longer ( median duration 16 vs. 10 weeks , P = 0.01 ) . No important differences in ORR , time-to-progression or median survival were observed . Grade 3 + 4 toxicity was significantly higher in the PV-group for leukopenia ( P = 0.0003 ) , neutropenia ( P < 0.0001 ) , nausea/vomiting ( P = 0.0006 ) , alopecia ( P < 0.0001 ) , and neurotoxicity ( P = 0.04 ) . Some severe pulmonary toxicity to GEM was noted . CONCLUSION Comparison of GEM with cisplatin-based therapy in symptomatic , advanced NSCLC demonstrates that GEM produces significantly a stronger and longer-lasting clinical benefit , probably due to its equal effectiveness in terms of ORR , time-to-progression or survival , combined with significantly less severe therapy-related toxicity BACKGROUND To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan ( IP ) in patients with untreated advanced non-small-cell lung cancer ( NSCLC ) by a non-inferiority design . PATIENTS AND METHODS A total of 602 patients were r and omly assigned to one of four regimens : cisplatin 80 mg/m(2 ) on day 1 plus irinotecan 60 mg/m(2 ) on days 1 , 8 , 15 every 4 weeks ( IP ) carboplatin AUC 6.0 min x mg/mL ( area under the concentration-time curve ) on day 1 plus paclitaxel 200 mg/m(2 ) on day 1 every 3 weeks ( TC ) ; cisplatin 80 mg/m(2 ) on day 1 plus gemcitabine 1000 mg/m(2 ) on days 1 , 8 every 3 weeks ( GP ) ; and cisplatin 80 mg/m(2 ) on day 1 plus vinorelbine 25 mg/m(2 ) on days 1 , 8 every 3 weeks ( NP ) . RESULTS The response rate , median survival time , and 1-year survival rate were 31.0 % , 13.9 months , 59.2 % , respectively , in IP ; 32.4 % , 12.3 months , 51.0 % in TC ; 30.1 % , 14.0 months , 59.6 % in GP ; and 33.1 % , 11.4 months , 48.3 % in NP . No statistically significant differences were found in response rate or overall survival , but the non-inferiority of none of the experimental regimens could be confirmed . All the four regimens were well tolerated . CONCLUSION The four regimens have similar efficacy and different toxicity profiles , and they can be used to treat advanced NSCLC patients BACKGROUND Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . Some studies have also suggested that gemcitabine is well tolerated and effective in such patients . We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label , r and omized phase III trial in elderly patients with advanced NSCLC . METHODS Patients aged 70 years and older , enrolled between December 1997 and November 2000 , were r and omly assigned to receive intravenous vinorelbine ( 30 mg/m(2 ) of body surface area ) , gemcitabine ( 1200 mg/m(2 ) ) , or vinorelbine ( 25 mg/m(2 ) ) plus gemcitabine ( 1000 mg/m(2 ) ) . All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles . The primary endpoint was survival . Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test . Secondary endpoints were quality of life and toxicity . RESULTS Of 698 patients available for intention-to-treat analysis , 233 were assigned to receive vinorelbine , 233 to gemcitabine , and 232 to vinorelbine plus gemcitabine . Compared with each single drug , the combination treatment did not improve survival . The hazard ratio of death for patients receiving the combination treatment was 1.17 ( 95 % confidence interval [ CI ] = 0.95 to 1.44 ) that of patients receiving vinorelbine and 1.06 ( 95 % CI = 0.86 to 1.29 ) that of patients receiving gemcitabine . Although quality of life was similar across the three treatment arms , the combination treatment was more toxic than the two drugs given singly . CONCLUSION The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC BACKGROUND In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1 - 2 months on median survival versus best supportive care . Chemotherapy seems to improve symptoms control , even if r and omised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio . The aim of the present study is to evaluate the impact on QoL , substituting cisplatin , a pivot drug in NSCLC therapy , with carboplatin , an analogue with an improved toxicity profile . The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study . METHODS Patients were r and omized to receive MVP regimen ( Mitomycin-C 8 mg/m2 d1 , Vinblastine 4 mg/m2 d 1 - 8 , Cisplatin 100 mg/m2 d1 ) or MVC regimen ( Mitomycin-C 8 mg/m2 d1 , Vinblastine 4 mg/m2 d 1 - 8 , Carboplatin 300 mg/m2 d1 ) every 3 weeks . The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 question naires before chemotherapy , after one cycle , after three cycles , and then every 6 weeks in the first 6 months and every 3 months thenafter . RESULTS From September 1994 to July 1997 , 153 consecutive patients were r and omized to MVP ( 75 patients ) or MVC arm ( 78 patients ) . Despite difficulties in carrying out and analysing QoL items in such patients , the global QoL evaluated by the Spitzer 's question naire suggested an advantage for MVC regimen ( P=0.05 ) and a significant difference was observed in global health subdomain ( P=0.04 ) . The disease-related symptoms improved with time , and the benefits lasted for the entire treatment period . When evaluated with the EORTC question naire there was significantly less nausea and vomiting ( P=0.0001 ) , appetite loss ( P=0.01 ) , insomnia ( P=0.03 ) , constipation ( P=0.01 ) and peripheral neuropathy ( P=0.01 ) in favour of MVC , and a trend for less hair loss ( P=0.05 ) . The advantage lasted for all the duration of chemotherapy . No differences were observed in global quality of life subdomain ( P=0.40 ) between the two regimen . QoL was the first endpoint and the statistical power was inadequate to assess other parameters . However , we reported a response rate of 43.1 and 38.6 % , respectively , in MVP and MVC arm ( P=0.59 ) and a median survival of 10.2 and 7.2 months , respectively , for cisplatin and carboplatin arm ( P=0.39 ) . CONCLUSIONS The carboplatin containing regimen ( MVC ) has a significant better toxicity profile than the cisplatin containing ( MVP ) regimen as proven both by the EORTC question naires and by the WHO toxicity data reported by physicians . No significant differences in terms of response rate , time to progression and overall survival were observed between the two regimen . The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL question naire . With the Spitzer 's question naires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination . This difference , however , was not observed when the global quality of life was evaluated with the EORTC patients compiled question naires . A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC Background : We conducted a multicenter r and omized phase II trial to evaluate two schedules of single-agent docetaxel in the first-line treatment of elderly and performance status ( PS ) 2 patients with advanced non-small cell lung cancer ( NSCLC ) . Methods : Patients 70 years of age and older with a PS 0–1 or patients of any age and PS 2 were r and omly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks or 30 mg/m2 on days 1 , 8 , and 15 every 28 days . The primary end point was frequency of grade 3/4 toxicities . Health-related quality of life , response , and survival were secondary end points . Results : Fifty-five patients were r and omized to received docetaxel every 3 weeks and 56 to receive docetaxel weekly . Hematologic toxicity , primarily grade 3/4 neutropenia , was significantly lower in the weekly schedule ( 0 % versus 44 % ; p < 0.001 ) . Health-related quality of life was similar between the two arms . Efficacy parameters were not significantly different , with a trend toward better survival in the weekly schedule group ( 6.7 versus 3.5 months ) . Patients with PS 0–1 had a significantly longer survival compared with PS 2 patients ( 7.8 versus 2.9 months ; p < 0.001 ) . A subset analysis of 30 octogenarian patients revealed similar outcomes as in 70- to 79-year-old patients . Conclusion : Weekly docetaxel is associated with less neutropenia and a trend toward improved survival in elderly or PS 2 patients . PS rather than age is the primary determinant of outcome in this population . Octogenarians benefited from weekly docetaxel . Future studies should separate elderly patients from PS 2 patients 5030 Background : Topotecan combined with etoposide ( GINECO 1998 ) and gemcitabine ( NOGGO 2001 ) proved effective for second-line treatment of recurrent ovarian cancer . It is , however , unclear whether combined treatment improves survival and tumor control compared to topotecan alone . METHODS Women with recurrent ovarian cancer after primary surgery and platinum therapy were enrolled in an open-label r and omized phase-III trial at 93 German institutions . Stratifying for treatment-free intervals ( TFI ) of less or more than 12 months , subjects were central ly allocated to topotecan 1.25 mg/m2/d ( TM ) , topotecan 1.0 mg/m2/d plus oral etoposide 50 mg/d ( TE ) on day 6 - 12 , or topotecan 0.5 mg/m2/d plus gemcitabine ( TG ) 800 mg/m2/d1 and 600 mg/m2/d8 every three weeks . Local institutional review boards approved this study , and all patients provided written informed consent . With 145 subjects each arm , this study yielded 90 % power to detect a Hazard Ratio ( HR ) of 0.60 in overall survival ( OS ) at a two-sided alpha of 0.01 . We employed Cox regression for primary endpoint analysis , and addressed progression-free survival ( PFS ) and toxicity descriptively . RESULTS Between September 1999 and November 2004 , 3036 courses were administered to 505 patients ( mean age 60.4 [ SD 11.3 ] years ) , 208 of whom had a TFI < 12 months . Women assigned to TM , TE , and TG received a median of 6.7 ( range , 0 - 10 ) , 6.2 ( 0 - 9 ) , and 5.4 ( 1 - 42 ) cycles . Median OS after TM , TE , and TG was 17.8 , 17.8 , and 15.3 months . Setting TM as the reference , HRs for OS with TE and TG were 1.13 ( 95 % confidence interval [ CI ] 0.87 - 1.47 ) and 1.07 ( 95 % CI 0.80 - 1.43 , p = 0.590 ) . HRs for PFS with TE and TG versus TM were calculated at 0.84 ( 95 % CI 0.66 - 1.07 ) each . Subgroup analysis suggested enhanced PFS among subjects with TFI ≥12 months who received TE ( HR 0.62 , 95 % CI 0.42 - 0.91 ) or TG ( HR 0.68 , 95 % CI 0.46 - 1.01 ) rather than TM . TE produced higher CTC grade 3/4 hematotoxicity than TM or TG , with cumulative incidences of 24.4 % ( 95 % CI 20.2 - 29.0 % ) , 16.0 % ( 95 % CI 11.9 - 20.9 % ) , and 14.7 % ( 10.6 - 19.5 % ) . CONCLUSIONS This large RCT does not provide evidence that combined treatment performs generally better than topotecan monotherapy in recurrent ovarian cancer . No significant financial relationships to disclose AIMS It has been recommended that closeness to death is considered when design ing and reporting quality -of-life ( QoL ) studies in patients with advanced cancer . The aim of this work was to assess whether this finding holds when adjusting for previous QoL. MATERIAL S AND METHODS The study sample comprised 107 advanced non-small cell lung cancer patients r and omised to the Big Lung Trial-QoL Study . Baseline and week 12 QoL data and patient characteristics were considered . Univariate and multivariate analysis of week 12 QoL considered baseline QoL scores , closeness to death , patient characteristics and treatment . RESULTS Univariate analyses showed significantly different week 12 QoL according to closeness to death for nine of 15 QoL domains . Multivariate analyses showed closeness to death to be independently predictive of only three QoL domains , with performance status and baseline QoL being more predominant . CONCLUSIONS In the present study , closeness to death was not found to be as important a factor in multivariate analysis as previously found . We recommend that previous QoL and performance status are considered in the design and analysis of QoL studies in which QoL is assessed at multiple time points in patients with advanced cancer , and that closeness to death may also be considered Introduction : This study evaluated the safety/efficacy of once-weekly ( QW ) epoetin alfa measured by quality of life ( QOL ) , hemoglobin ( Hb ) , transfusion incidence , tumor response , and survival in patients with chemotherapy-naïve , advanced non-small cell lung cancer ( NSCLC ) . Methods : Stage IIIB/IV NSCLC patients with Hb ≥11 to < 15 g/dl scheduled for at least 8 weeks of first-line chemotherapy were r and omized to subcutaneously receive 40,000 U of epoetin alfa QW at chemotherapy initiation ( immediate ) or no epoetin alfa unless Hb decreased to ≤10 g/dl ( delayed ) . The primary efficacy variable was change in QOL for immediate versus delayed intervention . Target accrual was 320 patients . Results : The study was terminated early because of slow accrual ; of 216 patients enrolled , 211 were evaluable for efficacy . Hb was maintained in the immediate group , but it decreased in the delayed group ( 12.9 versus 11.6 g/dl final values , respectively ) . Numerically , fewer immediate patients required transfusions versus delayed patients . Mean QOL scores , modestly declining in both groups from baseline to final measurement , were not significantly different between groups . Tumor response and median overall survival were similar between groups . Epoetin alfa was well tolerated , with a similar thrombovascular event rate between groups . Conclusion : Epoetin alfa in subcutaneous doses of 40,000 U QW , given immediately at chemotherapy initiation for advanced NSCLC , was well tolerated , and it effectively maintained Hb , leading to a reduced transfusion incidence versus delayed epoetin alfa . Overall QOL scores were higher than typical in this population , decreasing slightly during treatment in both groups . Overall survival was similar between groups , with no evidence of a negative effect by early epoetin alfa intervention Background : Patients with poor performance status and /or are elderly are frequently considered a compromised group at high risk of chemotherapy-related morbidities and less likely to benefit from treatment . We aim ed to evaluate tolerability and efficacy of three single-agent regimens in these patients . Patients and Methods : Patients with advanced non-small cell lung cancer who had performance status 2/3 and /or were aged 70 and older were r and omly assigned to receive gemcitabine , vinorelbine , or docetaxel . Objective response , toxicities , and quality of life were evaluated . Results : One hundred thirty-five patients were registered , of whom one was ineligible . Of the 134 patients , 43 received gemcitabine , 45 vinorelbine , and 46 docetaxel . The response rate was 16 % , 20 % , 22 % for gemcitabine , vinorelbine , and docetaxel , respectively . The main grade 3/4 toxicities were fatigue ( 18 % ) and neutropenia ( 16 % ) . There was improvement in global health scores , cough , and dyspnea for all treatment groups . The improvement in dyspnea was most marked in patients with performance status 3 . Conclusion : There was no significant advantage of any of the treatment arms over the rest . There was benefit seen with improvement of quality of life in patients who were able to receive more cycles of chemotherapy BACKGROUND The optimal schedule of taxane administration has been an area of active interest in several recent clinical trials . METHODS To address a pure schedule question , we r and omized 161 patients with advanced stage IIIB or IV non-small-cell lung cancer ( NSCLC ) to either paclitaxel 225 mg/m2 every 3 weeks x 4 cycles or 75 mg/m2/week x 12 ( cumulative dose on each arm = 900 mg/m2 ) . Both arms received concurrent carboplatin AUC 6 every 3 weeks x 4 cycles . RESULTS The two arms were well-balanced in terms of known prognostic factors . The overall response rate and survival outcomes were similar on the two arms . There was significantly more grade 3/4 thrombocytopenia and grade 2 - 4 anemia on the weekly arm but less severe myalgias/arthralgias and alopecia . No difference in the rates of peripheral neuropathy was observed ; however , patients on the every 3 weeks arm reported significantly more taxane therapy-related side-effects on the functional assessment of cancer therapy taxane subscale . CONCLUSIONS This r and omized trial exploring schedule-related issues with carboplatin/paclitaxel confirms the versatility of this regimen PURPOSE This trial was conducted to determine the optimal duration of chemotherapy in Korean patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with stages IIIB to IV NSCLC who had not progressed after two cycles of chemotherapy were r and omly assigned to receive either four ( arm A ) or two ( arm B ) more cycles of third-generation , platinum-doublet treatment . RESULTS Of the 452 enrolled patients , 314 were r and omly assigned to the groups . One-year survival rates were 59.0 % in arm A and 62.4 % in arm B , and the difference of 3.4 % ( 95 % CI , -8.0 to 4.8 ) met the predefined criteria for noninferiority . The median time to progression ( TTP ) , however , was 6.2 months ( 95 % CI , 5.7 to 6.7 months ) in arm A and 4.6 months ( 95 % CI , 4.4 to 4.8 months ) in arm B , the difference of which is statistically significant ( P = .001 ) . The frequencies of hematologic and nonhematologic toxicities were similar in the two arms . CONCLUSION This study confirms the noninferiority of overall survival with four cycles compared with six cycles of chemotherapy for the first-line treatment of advanced NSCLC and supports the current American Society of Clinical Oncology guidelines . Notably , patients receiving six cycles of chemotherapy compared with four cycles showed a favorable TTP , suggesting that further investigation of the new strategies of maintenance therapy with less toxic agents after three to four cycles of induction chemotherapy might be warranted to improve survival , with consideration of both ethnicity and pharmacogenomic signatures PURPOSE This study assessed whether maintenance therapy with carboxyaminoimidazole ( CAI ) , compared to placebo , prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen . METHODS After completion of chemotherapy , patients were r and omized to receive daily oral CAI at 250 mg or placebo . Treatment continued until patient refusal , disease progression or unacceptable adverse event ( AE ) . Quality of life ( QOL ) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer ( FACT-L ) . RESULTS Registration was halted early for slow accrual ( targeted 360 , r and omized 186 : 94 CAI , 92 placebo ) . All patients were off active treatment at time of analyses . Non-haematologic AEs ( primarily grade 1 , 2 ) observed significantly more often in the CAI group included fatigue ( 54.5 % versus 29.3 % ) , anorexia ( 31.1 % versus 13.0 % ) , nausea ( 62.2 % versus 30.4 % ) , vomiting ( 32.2 % versus 14.1 % ) , neurosensory ( 60.0 % versus 44.6 % ) and ataxia ( 33.3 % versus 16.3 % ) . Patients discontinued treatment for AEs , death on study or refusal more often in the CAI group ( 36.0 % versus 8.7 % , p<0.0001 ) . No significant differences in survival or time to progression were observed ( median : CAI versus placebo : 11.4 months versus 10.5 months , log rank p=0.54 ; 2.8 months versus 2.4 months , log rank p=0.50 ) . More patients receiving CAI reported a clinical ly significant ( 10-point ) decline in QOL particularly on the functional ( 58 % versus 37 % , p=0.05 ) construct of FACT-L and UNISCALE ( 72 % versus 51 % , p=0.04 ) . CONCLUSION The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC PURPOSE This r and omized phase II study compared two treatment schedules of gemcitabine in patients with non-small-cell lung cancer ( NSCLC ) and impaired Karnofsky performance status ( KP ) . Primary objectives were to record changes from baseline KP and to assess symptom palliation . Secondary objectives were overall survival , tumor response , and toxicity . PATIENTS AND METHODS Patients with stage IIIb and IV NSCLC and KP < /= 70 were r and omly assigned to receive gemcitabine 1,000 mg/m(2 ) on days 1 , 8 , and 15 of each 28-day cycle ( 3w4 ) or gemcitabine 1,500 mg/m(2 ) on days 1 and 8 of each 21-day cycle ( 2w3 ) , both for up to six cycles . KP , toxicity , and SS14 lung cancer specific questions were recorded before each cycle of treatment . Response was evaluated 4 weeks after the last cycle . RESULTS One hundred seventy-four patients were enrolled . There was significant early attrition due to disease progression ; only 61.5 % of patients were alive at 2 months . There was a significant improvement in KP from baseline to pre-cycle 3 in both arms , with a trend in favor of the 3w4 regimen for duration and faster onset of improvement . Eight of the 17 quality -of-life ( QOL ) variables assessed showed an improvement of more than 10 % between baseline and the start of the third cycle of treatment . Response rate , survival , and duration were similar in both arms . CONCLUSION There was no significant difference between the two schedules examined in terms of improvement in KP or QOL , but there seemed to be a trend in favor of the 3w4 schedule Abstract Objective : To determine whether patients with locally advanced non-small cell lung cancer unsuitable for resection or radical radiotherapy , and with minimal thoracic symptoms , should be given palliative thoracic radiotherapy immediately or as needed to treat symptoms . Design : Multicentre r and omised controlled trial . Setting : 23 centres in the United Kingdom , Irel and , and South Africa . Participants : 230 patients with previously untreated , non-small cell lung cancer that is locally too advanced for resection or radical radiotherapy with curative intent , with minimal thoracic symptoms , and with no indication for immediate thoracic radiotherapy . Interventions : All patients were given supportive treatment and were r and omised to receive palliative thoracic radiotherapy either immediately or delayed until needed to treat symptoms . The recommended regimens were 17 Gy in two fractions one week apart or 10 Gy as a single dose . Main outcome measures : Primary — patients alive and without moderate or severe cough , chest pain , haemoptysis , or dyspnoea six months from r and omisation , as recorded by clinicians . Secondary — quality of life , adverse events , survival . Results : From December 1992 to May 1999 , 230 patients were r and omised . 104/115 of the patients in the immediate treatment group received thoracic radiotherapy ( 90 received one of the recommended regimens ) . In the delayed treatment group , 48/115 ( 42 % ) patients received thoracic radiotherapy ( 29 received one of the recommended regimens ) ; 64 ( 56 % ) died without receiving thoracic radiotherapy ; the remaining three ( 3 % ) were alive at the end of the study without having received the treatment . For patients who received thoracic radiotherapy , the median time to start was 15 days in the immediate treatment group and 125 days in the delayed treatment group . The primary outcome measure was achieved in 28 % of the immediate treatment group and 26 % of patients from the delayed treatment group ( 27/97 and 27/103 , respectively ; absolute difference 1.6 % , 95 % confidence interval -10.7 % to 13.9 % ) . No evidence of a difference was observed between the two treatment groups in terms of activity level , anxiety , depression , and psychological distress , as recorded by the patients . Adverse events were more common in the immediate treatment group . Neither group had a survival advantage ( hazard ratio 0.95 , 0.73to 1.24 ; P=0.71 ) . Median survival was 8.3 months and 7.9 months , and the survival rates were 31 % and 29 % at 12 months , for the immediate and delayed treatment groups , respectively . Conclusion : In minimally symptomatic patients with locally advanced non-small cell lung cancer , no persuasive evidence was found to indicate that giving immediate palliative thoracic radiotherapy improves symptom control , quality of life , or survival when compared with delaying until symptoms require treatment PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine ( DG ) and vinorelbine/cisplatin ( VC ) combinations in chemotherapy-naive non-small-cell lung cancer ( NSCLC ) patients . PATIENTS AND METHODS Patients with advanced NSCLC were r and omly assigned to receive either DG ( gemcitabine 1,000 mg/m(2 ) [ days 1 and 8 ] plus docetaxel 100 mg/m(2 ) [ day 8 ] ) or VC ( vinorelbine 30 mg/m(2 ) [ days 1 and 8 ] plus cisplatin 80 mg/m(2 ) [ day 8 ] ) and prophylactic recombinant human granulocyte colony-stimulating factor ( 150 microg/m(2 ) subcutaneously [ day 9 through 15 ] ) every 3 weeks . Results A total of 413 r and omly assigned patients were analyzed for response and toxicity ( DG , n = 197 ; VC , n = 192 ) . Median survival was 9.0 and 9.7 months ( P = .965 ) for DG and VC arms , respectively ; the corresponding 1-year survival rates were 34.3 % and 40.8 % , respectively . Overall response rate was 30 % ( 95 % CI , 23.9 % to 36.3 % ) and 39.2 % ( 95 % CI , 32.5 % to 45.9 % ; P = .053 ) for DG and VC , respectively . Toxicity was as follows ( DG v VC ) : grade 2 to 4 anemia , 34 % v 55 % ( P = .0001 ) ; grade 3 to 4 neutropenia , 16 % v 37 % ( P = .0001 ) ; febrile neutropenia , 6 % v 11 % ( P = .009 ) ; and grade 3 to 4 nausea and vomiting , 1 % v 15 % ( P = .003 ) . Nephrotoxicity occurred in 8 % and ototoxicity in 2 % of VC-treated patients . There were five and six treatment-related deaths in the DG and VC arms , respectively . Quality of life was improved in DG but not in VC patients . CONCLUSION Although the two regimens produced comparable overall survival , the DG regimen had a better toxicity profile . Therefore , DG could be used in the first-line setting of advanced NSCLC , especially for patients who can not tolerate cisplatin To compare the overall survival ( OS ) of patients with advanced non-small cell lung ( NSCLC ) treated with either docetaxel plus gemcitabine or single-agent docetaxel . Chemotherapy-naive patients with advanced/metastatic NSCLC were r and omly assigned to receive either DG [ n=157 ; gemcitabine 1100mg/m(2 ) on days 1 and 8 ] , docetaxel 75mg/m(2 ) on day 8 or D [ n=155 ; docetaxel 100mg/m(2 ) on day 1 ] every 3 weeks . A total of 312 patients were evaluable for toxicity and response . A predefined interim intention-to-treat analysis showed significantly longer median OS ( p=0.037 ) in favor of the DG regimen ( 9.4 months versus 8.3 months for DG and D regimens , respectively ) , result ing in the premature termination of the study . The DG regimen was also associated with a significantly higher response rate compared to D ( 26.8 % versus 11.6 % , p<0.001 ) . TTP were 3.5 and 2.3 months for the DG and D regimen , respectively ( p=0.054 ) . Although there were two treatment-related deaths in the DG arm , the toxicity profiles of the two regimens were comparable . The DG regimen was associated with a significantly better quality of life . The efficacy of the docetaxel plus gemcitabine combination is superior to single-agent docetaxel in chemonaive patients with advanced NSCLC PURPOSE To investigate whether the effect of hypofractionated thoracic radiotherapy ( TRT ) is comparable to more st and ard fractionated radiotherapy ( RT ) in advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 421 patients with locally advanced stage III or stage IV NSCLC tumors were included . Inclusion criteria were inoperable , disease too advanced for curative radiotherapy , and chest symptoms or central tumor threatening the airways . Patients were r and omly assigned to three arms : A , 17 Gy per two fractions ( n = 146 ) ; B , 42 Gy per 15 fractions ( n = 145 ) ; and C , 50 Gy per 25 fractions ( n = 130 ) . Four hundred seven patients were eligible for the study ; 395 patients ( 97 % ) participated in the health-related quality -of-life ( HRQOL ) study . The European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire (QLQ)-C30 and EORTC QLQ-lung cancer-specific module ( LC13 ) were used to investigate airway symptom relief and changes in HRQOL . Assessment s were performed before TRT and until week 54 . Clinicians ' assessment s of symptom improvement were at 2 , 6 , and 14 weeks after completion of TRT . The patients were observed for a minimum of 3 years . Results Baseline prognostic data were equally distributed in the treatment groups . Patient compliance with respect to the HRQOL investigation was minimum 74 % . HRQOL and symptom relief were equivalent in the treatment arms . No significant difference in survival among arms A , B , and C was found , with median survival 8.2 , 7.0 , and 6.8 months , respectively . CONCLUSION Our data indicate that protracted palliative TRT renders no improvement in symptom relief , HRQOL , or survival when compared with short-term hypofractionated treatment in advanced NSCLC PURPOSE This phase III r and omized trial compared two chemotherapy regimens , gemcitabine plus carboplatin and mitomycin , ifosfamide , and cisplatin , in chemotherapy-naive patients with advanced non-small-cell lung cancer ( NSCLC ) . The regimens were compared with regard to effects on survival , response rates , toxicity , and quality of life . PATIENTS AND METHODS Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy . R and omly assigned patients were to receive four cycles , each at 3-week intervals , of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2 ) on days 1 and 8 ( GCa ) or mitomycin 6 mg/m(2 ) , ifosfamide 3g/m(2 ) , and cisplatin 50 mg/m(2 ) on day 1 ( MIC ) . RESULTS Between February 1999 and August 2001 , 422 patients ( GCa , n = 212 ; MIC , n = 210 ) were r and omly assigned in the United Kingdom . The majority of patients received the intended four cycles ( GCa , 64 % ; MIC , 61 % ) . There was a significant survival advantage for GCa compared with MIC ( hazard ratio , 0.76 ; 95 % CI , 0.61 to 0 . 93 ; P = .008 ) . Median survival was 10 months with GCa and 7.6 months with MIC ( difference , 2.4 months ; 95 % CI , 1.0 to 4.0 ) , and 1-year survival was 40 % with GCa and 30 % with MIC ( difference , 10 % ; 95 % CI , 3 % to 18 % ) . Overall response rates were similar ( 42 % for GCa v 41 % for MIC ; P = .84 ) . More thrombocytopenia occurred with GCa ( P = .03 ) , but this was not associated with increased hospital admission or fatality . GCa caused less nausea , vomiting , constipation , and alopecia and was associated with fewer admissions for administration and better quality of life . CONCLUSION In patients with advanced NSCLC , GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC BACKGROUND Phase III studies suggest that non-small-cell lung cancer ( NSCLC ) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens . We report the final results of a r and omised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC . PATIENTS AND METHODS Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were r and omised to receive four cycles of either DCb ( docetaxel 75 mg/m(2 ) , carboplatin AUC 6 ) , or MIC/MVP ( mitomycin 6 mg/m(2 ) , ifosfamide 3 g/m(2 ) and cisplatin 50 mg/m(2 ) or mitomycin 6 mg/m(2 ) , vinblastine 6 mg/m(2 ) and cisplatin 50 mg/m(2 ) , respectively ) , 3 weekly . The primary end point was survival , secondary end points included response rates , toxicity and quality of life . RESULTS The median follow-up was 17.4 months . Overall response rate was 32 % for both arms ( partial response = 31 % , complete response = 1 % ) ; 32 % of MIC/MVP and 26 % of DCb patients had stable disease . One-year survival was 39 % and 35 % for DCb and MIC/MVP , respectively . Two-year survival was 13 % with both arms . Grade 3/4 neutropenia ( 74 % versus 43 % , P < 0.005 ) , infection ( 18 % versus 9 % , P = 0.01 ) and mucositis ( 5 % versus 1 % , P = 0.02 ) were more common with DCb than MIC/MVP . The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change . CONCLUSIONS The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained PURPOSE To compare pemetrexed/carboplatin with a st and ard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC . PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were r and omly assigned to receive pemetrexed 500 mg/m(2 ) plus carboplatin area under the curve ( AUC ) = 5 ( Calvert 's formula ) on day 1 or gemcitabine 1,000 mg/m(2 ) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles . The primary end point was health-related quality of life ( HRQoL ) defined as global quality of life , nausea/vomiting , dyspnea , and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and the lung cancer-specific module LC13 during the first 20 weeks . Secondary end points were overall survival and toxicity . Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006 . Patients who completed the baseline question naire were analyzed for HRQoL ( n = 427 ) , and those who received > or = one cycle of chemotherapy were analyzed for toxicity ( n = 423 ) . Compliance of HRQoL question naires was 87 % . There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms ( pemetrexed/carboplatin , 7.3 months ; gemcitabine/carboplatin , 7.0 months ; P = .63 ) . The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin , including leukopenia ( 46 % v 23 % , respectively ; P < .001 ) , neutropenia ( 51 % v 40 % , respectively ; P = .024 ) , and thrombocytopenia ( 56 % v 24 % , respectively ; P < .001 ) . More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets , whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms . CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care PURPOSE Few r and omized trials have demonstrated survival benefit of combination chemotherapy involving new agents plus cisplatin compared with classic combination chemotherapy in advanced non-small-cell lung cancer ( NSCLC ) . The primary aim of this study was to test whether docetaxel plus cisplatin ( DC ) improves survival compared with vindesine plus cisplatin ( VdsC ) in patients with previously untreated stage IV NSCLC . PATIENTS AND METHODS Eligible , stage IV , chemotherapy-naive patients ( n = 311 ) were r and omly assigned to receive docetaxel 60 mg/m(2 ) intravenously on day 1 plus cisplatin 80 mg/m(2 ) intravenously on day 1 of a 3- or 4-week cycle , or vindesine 3 mg/m(2 ) intravenously on days 1 , 8 , and 15 plus cisplatin 80 mg/m(2 ) intravenously on day 1 of a 4-week cycle . Cross-over administration of docetaxel and vindesine was prohibited for both treatment groups . RESULTS Overall , 302 patients were eligible for evaluation . The DC arm demonstrated significant improvements compared with the VdsC arm in overall response rates ( 37 % v 21 % , respectively ; P < .01 ) and median survival times ( 11.3 v 9.6 months , respectively ; P = .014 ) . Two-year survival rates were 24 % for the DC arm compared with 12 % for the VdsC arm . The physical domain of the Quality of Life for Cancer Patients Treated with Anticancer Drugs measure was significantly better in the DC arm than in the VdsC arm ( P = .020 ) . Toxicity was predominantly hematologic and was more severe in the VdsC arm . CONCLUSION As first-line treatment for stage IV NSCLC , DC result ed in greater clinical benefit in terms of response rate ( with marked improvements in overall and 2-year survival rates ) and quality of life than did treatment with PURPOSE This phase II , open-label , parallel-group study compared gefitinib with vinorelbine in chemotherapy-naïve elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . METHODS Chemotherapy-naïve patients ( age > or= 70 years ) were r and omly assigned to gefitinib ( 250 mg/d orally ) or vinorelbine ( 30 mg/m(2 ) infusion on days 1 and 8 of a 21-day cycle ) . The primary end point was progression-free survival ( PFS ) . Secondary end points were overall survival ( OS ) , objective response rate ( ORR ) , quality of life ( QOL ) , pulmonary symptom improvement ( PSI ) , and tolerability . Exploratory end points included epidermal growth factor receptor ( EGFR ) gene copy number by fluorescent in situ hybridization ( FISH ) . RESULTS Patients were r and omly assigned to gefitinib ( n = 97 ) or to vinorelbine ( n = 99 ) . Hazard ratios ( HR ; gefitinib v vinorelbine ) were 1.19 ( 95 % CI , 0.85 to 1.65 ) for PFS and 0.98 ( 95 % CI , 0.66 to 1.47 ) for OS . ORR and disease control rates were 3.1 % ( 95 % CI , 0.6 to 8.8 ) and 43.3 % ( for gefitinib ) and 5.1 % ( 95 % CI , 1.7 to 11.4 ) and 53.5 % ( for vinorelbine ) , respectively . Overall QOL improvement and PSI rates were 24.3 % and 36.6 % ( for gefitinib ) and 10.9 % and 31.0 % ( for vinorelbine ) , respectively . In the 54 patients who were EGFR FISH-positive , HRs were 3.13 ( 95 % CI , 1.45 to 6.76 ) for PFS and 2.88 ( 95 % CI , 1.21 to 6.83 ) for OS . There were fewer treatment-related grade 3 to 5 adverse events with gefitinib ( 12.8 % ) than with vinorelbine ( 41.7 % ) . CONCLUSION There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy-naïve , unselected elderly patients with advanced NSCLC , but there was better tolerability with gefitinib . Individuals who were EGFR FISH-positive benefited more from vinorelbine than from gefitinib ; this unexpected finding requires further study Background : In 1995 a meta- analysis of r and omised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer ( NSCLC ) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment setting s. However , the meta- analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens . Methods : The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta- analysis and to assess quality of life and cost in the supportive care setting . A total of 725 patients were r and omised to receive supportive care alone ( n = 361 ) or supportive care plus cisplatin-based chemotherapy ( n = 364 ) . Results : 65 % of patients allocated chemotherapy ( C ) received all three cycles of treatment and a further 27 % received one or two cycles . 74 % of patients allocated no chemotherapy ( NoC ) received thoracic radiotherapy compared with 47 % of the C group . Patients allocated C had a significantly better survival than those allocated NoC : HR 0.77 ( 95 % CI 0.66 to 0.89 , p = 0.0006 ) , median survival 8.0 months for the C group v 5.7 months for the NoC group , a difference of 9 weeks . There were 19 ( 5 % ) treatment related deaths in the C group . There was no evidence that any subgroup benefited more or less from chemotherapy . No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points , although large negative effects of chemotherapy were ruled out . The regimens used proved to be cost effective , the extra cost of chemotherapy being offset by longer survival . Conclusions : The survival benefit seen in this trial was entirely consistent with the NSCLC meta- analysis and subsequent similarly design ed large trials . The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices PURPOSE To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life ( QoL ) in advanced non-small-cell lung cancer ( NSCLC ) compared with vinorelbine plus cisplatin as first-line chemotherapy . PATIENTS AND METHODS Patients ( n = 1,218 ) with stage IIIB to IV NSCLC were r and omly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks ( VC ) . RESULTS Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients ( P = .044 ; hazard ratio , 1.183 [ 97.2 % confidence interval , 0.989 to 1.416 ] ) . The 2-year survival rate was 21 % for DC-treated patients and 14 % for VC-treated patients . Overall response rate was 31.6 % for DC-treated patients v 24.5 % for VC-treated patients ( P = .029 ) . Median survival ( 9.4 v 9.9 months [ for VC ] ; P = .657 ; hazard ratio , 1.048 [ 97.2 confidence interval , 0.877 to 1.253 ] ) and response ( 23.9 % ) with DCb were similar to those results for VC . Neutropenia , thrombocytopenia , infection , and febrile neutropenia were similar with all three regimens . Grade 3 to 4 anemia , nausea , and vomiting were more common ( P < .01 ) with VC than with DC or DCb . Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients , who experienced deterioration in QoL. CONCLUSION DC result ed in a more favorable overall response and survival rate than VC . Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC . These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC BACKGROUND Patients with advanced non-small cell lung cancer ( NSCLC ) do not have curative treatment options ; therefore , treatments should prolong survival and improve quality of life ( QoL ) . We compared the effect on QoL of two docetaxel-platinum regimens with vinorelbine-cisplatin . METHODS QoL was assessed by the Lung Cancer Symptom Scale ( LCSS ) and the general EuroQol five-dimensional question naire ( EQ-5D ) in 926 chemotherapy-naïve patients with stages IIIB to IV NSCLC . Patients were r and omly assigned to receive : docetaxel 75 mg/m2 plus cisplatin 75 mg/m2 , every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin 6 mg/ml min , every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/week plus cisplatin 100 mg/m2 , every 4 weeks ( VC ) . RESULTS Overall , patients treated with either docetaxel-containing regimen had better QoL than VC-treated patients ( LCSS global item " QoL today " : P=0.064 for DC and P=0.016 for DCb versus VC ; EQ-5D global item " health state today " : P=0.016 for DC and P<0.001 for DCb versus VC ) . DC-treated patients experienced improved pain relief compared with VC ( P=0.033 ) , whereas pain relief with DCb and VC was similar . Patients treated with either docetaxel regimen had more favorable changes in performance status ( P=0.065 for DC and P<0.001 for DCb versus VC ) and mean weight loss ( 0.06 kg , gain of 0.08 kg , and 2.27 kg for DC , DCb , and VC , respectively ; P<0.001 for both DC versus VC and DCb versus VC ) . CONCLUSION The TAX 326 study shows that docetaxel-platinum regimens relieve symptoms and improve QoL in patients with advanced NSCLC . DCb and DC were superior to VC in all QoL outcomes assessed except for the difference between DC and VC in LCSS " QoL today " , which was not significant PURPOSE Platinum-containing chemotherapy regimens are the st and ard treatment for patients with advanced non-small-cell lung cancer ( NSCLC ) , although toxicity is common and may significantly affect the patient 's quality of life ( QoL ) . This trial aim ed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL , without influencing negatively on survival , compared with cisplatin-containing regimens . PATIENTS AND METHODS Patients with stage IIIB ( effusion and supraclavicular nodes ) or IV documented NSCLC who were younger than 70 years of age were r and omly assigned gemcitabine plus vinorelbine ( GemVin ) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin ( cisplatin-based ) . European Organization for Research and Treatment of Cancer scales were used for QoL analysis . RESULTS Five hundred one patients were r and omly assigned to treatment . The median age was 62 years . There were no significant differences in global QoL scores between the two arms after 2 months of treatment . However , worsening scores for appetite , vomiting , and alopecia were significantly more common in the cisplatin-based arm . Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms , respectively . For the GemVin arm the hazard ratio for death was 1.15 ( 90 % confidence interval [ CI ] , 0.96 to 1.37 ) and the hazard ratio for progression was 1.29 ( 90 % CI , 1.10 to 1.52 ) . Grade 3 or 4 myelosuppression , vomiting , alopecia , and ototoxicity were significantly more frequent with cisplatin-based treatment . CONCLUSION Global QoL is not improved with GemVin , although advantages in some components of QoL were apparent . GemVin is less toxic than st and ard cisplatin-based chemotherapy . There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy . GemVin could be offered to advanced NSCLC patients who express concern about toxicity PURPOSE To test the ability of the cytoprotectant , amifostine , to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life ( QOL ) and swallowing symptoms . PATIENTS AND METHODS A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2 ) intravenously ( IV ) days 1 and 22 and carboplatin area under the curve ( AUC ) days 1 and 22 , followed by concurrent weekly paclitaxel ( 50 mg/m(2 ) IV ) and carboplatin ( AUC 2 ) , and hyperfractionated radiation therapy ( 69.6 Gy at 1.2 Gy bid ) . Patients were r and omly assigned at registration to amifostine ( AM ) 500 mg IV four times per week or no AM during chemoradiotherapy . Beyond st and ard toxicity end points , physician dysphagia logs ( PDLs ) , daily patient swallowing diaries , and QOL ( EORTC QLQ-C30/LC-13 ) were also collected . Swallowing AUC analyses were calculated from patient diaries and PDLs . RESULTS A total of 120 patients were r and omly assigned to receive AM , and 122 , to receive no AM ( one patient was ineligible ) ; 72 % received AM per protocol or with a minor deviation . AM was associated with higher rates of acute nausea ( P = .03 ) , vomiting ( P = .007 ) , cardiovascular toxicity ( P = .0001 ) , and infection or febrile neutropenia ( P = .03 ) . The rate of > /= grade 3 esophagitis was 30 % with AM versus 34 % without AM ( P = .9 ) . Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine ( z test P = .025 ) . QOL was not significantly different between the two arms , except for pain , which showed more clinical ly meaningful improvement and less deterioration at 6 weeks follow-up ( v pretreatment ) in the AM arm ( P = .003 ) . The median survival rates for both arms were comparable ( AM , 17.3 v no AM , 17.9 months ; P = .87 ) . CONCLUSION AM did not significantly reduce esophagitis > /= grade 3 in patients receiving hyperfractionated radiation and chemotherapy . However , patient self- assessment s suggested a possible advantage to AM that is being explored with modified dosing route strategies BACKGROUND The addition of cyclo-oxygenase-2 ( COX-2 ) inhibitors and prolonged constant infusion ( PCI ) of gemcitabine to treatment for advanced non-small-cell lung cancer ( NSCLC ) might improve treatment efficacy . We aim ed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by st and ard infusion . METHODS Patients with stage IV or IIIb ( with supraclavicular nodes or pleural effusion ) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre , prospect i ve , open-label , r and omised phase III trial with 2 x 2 factorial design . Patients were r and omly assigned to one of four treatment groups : group A , gemcitabine 1200 mg/m(2 ) in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m(2 ) on day 1 , every 21 days for six cycles ; group B , the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression ; group C , intravenous PCI gemcitabine 1200 mg/m(2 ) in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m(2 ) on day 1 , every 21 days for six cycles ; group D , the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression . The primary endpoint was overall survival ; secondary endpoints were progression-free survival , response rate , quality of life , and toxicity . Analyses were intention-to-treat . This trial is registered on the clinical trials site of the US National Institutes of Health website http:// clinical trials.gov/ct/show/NCT00385606 . FINDINGS Between Jan 30 , 2003 , and May 3 , 2005 , 400 patients were enrolled . Median age was 60 years ( range 29 - 71 ) . PCI gemcitabine did not improve overall survival ( median 47 weeks [ 95 % CI 40 - 55 ] vs 44 [ 36 - 52 ] , with st and ard gemcitabine infusion , hazard ratio ( HR ) of death 0.93 [ 0.74 - 1.17 ] , p=0.41 ) , progression-free survival , nor any other secondary endpoint . Vomiting and fatigue were significantly worse with PCI gemcitabine . The two rofecoxib groups were closed early ( on Oct 1 , 2004 ) due to withdrawal of the drug because of safety issues . With intention-to-treat statistical analyses limited to 240 patients ( ie , those r and omised before July 1 , 2004 ) who had at least 3 months of treatment , rofecoxib did not prolong overall survival ( median 44 weeks [ CI 36 - 55 ] vs 44 [ 40 - 54 ] without rofecoxib , and HR of death 1.00 [ 0.75 - 1.34 ] , p=0.85 ) , or progression-free survival , but did improve response rate ( 41%vs 26 % , p=0.02 ) , global quality of life , physical , emotional and role functioning , fatigue , and sleeping . Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation , fatigue , fever , weight loss , and pain , and analgesic consumption . Severe cardiac ischaemia was more frequent with rofecoxib than without ; however , the difference was not statistically significant in the primary analysis ( p=0.06 ) and became significant when patients who were r and omised between July 1 , 2004 , and Sept 30 , 2004 , were included in the analysis ( p=0.03 ) . INTERPRETATION Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study . Rofecoxib improved response rate and several quality -of-life items , including pain-related items and global quality of life . Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC PURPOSE To determine the added value of quality of life ( QOL ) as a prognostic factor for overall survival ( OS ) in patients with locally advanced non-small-cell lung cancer ( NSCLC ) treated on Radiation Therapy Oncology Group RTOG-9801 . PATIENTS AND METHODS Two hundred forty-three patients with stage II/IIIAB NSCLC received induction paclitaxel and carboplatin ( PC ) and then concurrent weekly PC and hyperfractionated radiation ( to 69.6 Gy ) . Patients were r and omly assigned to amifostine ( AM ) or no AM during chemoradiotherapy . The following pretreatment factors were analyzed as prognostic factors for OS : Karnofsky performance status , stage , sex , age , race , marital status , histology , tumor location , hemoglobin , tobacco use , treatment arm ( AM v no AM ) and QOL scores ( European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 [ QLQ-C30 ] and Lung Cancer 13 [ LC-13 ] ) . A multivariate ( MVA ) Cox proportional hazards model was performed using a backwards selection process . RESULTS Of the 239 analyzable patients , 91 % had a baseline global QOL score . Median follow-up time was 59 months for patients still alive and 17 months for all patients . Median baseline QLQ-C30 global QOL score was 66.7 on both treatment arms . Whether the global QOL score was treated as a dichotomized variable ( based on the median score ) or a continuous variable , all other variables fell out of the MVA for OS . Patients with a global QOL score less than 66.7 had an approximately 70 % higher rate of death than patients with scores > or = 66.7 ( P = .004 ) . A 10-point higher baseline global QOL score corresponded to a decrease in the hazard of death by approximately 10 % ( P = .004 ) . The other independent QOL predictors for OS were the QLQ-C30 physical functioning ( P = .011 ) and LC-13 dyspnea scores ( P = .012 ) . CONCLUSION In this analysis , baseline global QOL score replaced known prognostic factors as the sole predictor of long-term OS for patients with locally advanced NSCLC BACKGROUND Cisplatin-induced anemia may correlate with adverse events , poor quality of life ( QoL ) , decreased adjuvant chemotherapy ( ACT ) dose intensity , shorter relapse-free survival ( RFS ) or overall survival ( OS ) . METHODS The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine ( n=242 ) compared to observation ( n=240 ) in patients with resected NSCLC [ Winton T , Livingston R , Johnson D , Rigas J , Johnston M , Butts C , et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer . N Engl J Med 2005;352(25):2640 - 2 ] . This exploratory analysis evaluates the predictive value of baseline ( in all patients ) and during-treatment ( in ACT arm only ) hemoglobin ( Hb ) levels on OS and RFS when adjusted for prognostic factors . Baseline ( in all patients ) and during treatment ( in ACT arm only ) Hb levels were also correlated with adverse events , QoL , morbidity and ACT dose intensity . RESULTS Baseline Hb did not predict RFS or OS . However , there was a trend to shorter OS ( p=0.1 ) when baseline Hb was < 120g/L. Lower baseline Hb predicted increased hospitalization ( p=0.04 ) and worse QoL ( SOB item , p=0.03 ) but had no impact on adverse events or dose intensity . There was a trend to longer RFS ( p=0.08 ) in patients with lower nadir during-treatment Hb and to longer OS ( p=0.06 ) and RFS ( p=0.08 ) in patients with maximum during-treatment Hb drop > 30 % that was not maintained when ACT dose intensity was included in the model . Maximum during-treatment Hb drop > 30 % correlated with increased lethargy ( p=0.003 ) and worse QoL ( fatigue item , p=0.07 ) . CONCLUSIONS Lower baseline and during-treatment Hb levels seem associated with poorer QoL , fatigue and increased hospitalization . There is a trend for shorter OS in patients with lower baseline Hb levels PURPOSE To evaluate whether cisplatin-based chemotherapy ( gemcitabine , vinorelbine , and cisplatin [ GVP ] ) prolongs overall survival in comparison to cisplatin-free chemotherapy ( gemcitabine and vinorelbine [ GV ] ) as first-line treatment in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Between September 1999 and June 2001 , 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were r and omly assigned to receive GV ( gemcitabine 1000 mg/m(2 ) + vinorelbine 25 mg/m(2 ) on days 1 and 8 every 3 weeks ) or GVP ( gemcitabine 1000 mg/m(2 ) + vinorelbine 25 mg/m(2 ) on days 1 and 8 + cisplatin 75 mg/m(2 ) on day 2 every 3 weeks ) . Primary end point of the study was overall survival . RESULTS Two hundred eighty-seven patients ( GV , 143 patients ; GVP , 144 patients ) were eligible for analysis . At the time of analysis , April 15 , 2002 , 209 patients ( GV , 103 patients ; GVP , 106 patients ) of 287 patients had died ( 73 % ) . No statistically significant difference was observed for overall survival ( P = .73 ; median survival , 35.9 versus 32.4 weeks ; 1-year survival rate , 33.6 % versus 27.5 % ) as well as for event-free survival ( P = .35 ; median time-to-event , 19.3 versus 22.3 weeks ) between GV and GVP . Two hundred fourteen patients were assessable for best response . The overall response rates were 13.0 % for GV versus 28.3 % for GVP ( P = .004 ; complete responders , 0 % versus 3.8 % ; partial responders , 13.0 % versus 24.5 % ) . Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP . No statistically significant difference in quality of life was observed . CONCLUSION In this phase III study , the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen , which was substantially better tolerated PURPOSE To compare the therapeutic efficacy of paclitaxel plus cisplatin ( arm A ) versus gemcitabine plus cisplatin ( arm B ) and arm A versus paclitaxel plus gemcitabine ( arm C ) in chemotherapy-naive patients with advanced non-small-cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Patients were r and omly assigned to receive either paclitaxel 175 mg/m2 ( 3-hour infusion , day 1 ) or gemcitabine 1,250 mg/m2 ( days 1 and 8) both combined with cisplatin 80 mg/m2 ( day 1 ) or paclitaxel 175 mg/m2 ( 3-hour infusion , day 1 ) combined with gemcitabine 1,250 mg/m2 ( days 1 and 8) . Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration , progression-free survival , toxicities , quality of life [ QoL ] , and cost of treatment . RESULTS Four hundred eighty patients ( arm A , 159 ; arm B , 160 ; arm C , 161 patients ) were enrolled ; all baseline characteristics were balanced . Median survival times were as follows : arm A , 8.1 months ; arm B , 8.9 months ; arm C , 6.7 months . Response rates were 31.8 % for arm A , 36.6 % for arm B , and 27.7 % for arm C. Other than myelosuppression ( B v A , P < .005 ) , no statistically or clinical ly significant differences were observed for secondary end points . The average treatment costs were 25 % higher in arm C as compared with arms A and B. CONCLUSION Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin . Treatment was well tolerated , and most QoL parameters were similar , but costs associated with the nonplatinum arm were highest BACKGROUND Chemotherapy has been widely accepted as st and ard for palliation in advanced non-small-cell lung cancer . Gemcitabine and docetaxel are active as single agents . Our previous experience indicates that single-agent therapy , if given sequentially , could be an alternative to doublet combination chemotherapy and that sequence and schedule matter . PATIENTS AND METHODS Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer were r and omized to receive first-line 3-weekly gemcitabine or docetaxel . At progression , patients received second-line therapy with the other agent . Treatment was considered feasible if 30 % of the evaluable patients had > or = 2 cycles of first-line and 2 cycles of second-line therapy and patient survival was > or = 7 months from the start of treatment . For efficacy , time to progression , overall survival , response , and quality of life were analyzed . RESULTS Three hundred thirty patients received gemcitabine followed by docetaxel or docetaxel followed by gemcitabine . Treatment was feasible for 60 patients ( 38 % ) with gemcitabine followed by docetaxel and for 80 patients ( 49 % ) with docetaxel followed by gemcitabine ; treatment favored docetaxel followed by gemcitabine ( P = 0.03539 ) . Median survival for gemcitabine followed by docetaxel and docetaxel followed by gemcitabine was 6.3 months and 8.6 months , and 1-year survival rate was 28 % and 31 % , respectively . Objective response rates were < or = 10 % for both treatment strategies . Quality of life was significantly better in gemcitabine followed by docetaxel ( P = 0.005 ) . CONCLUSION Single-agent gemcitabine and docetaxel are feasible as defined for both sequences but treatment favors docetaxel followed by gemcitabine . Thus , it is reasonable to state that single-agent therapy given sequentially might be a c and i date for palliation and therefore should be investigated in comparison with combination therapy PURPOSE A phase III r and omized trial was carried out to compare two schedules of the vinorelbine (VNR)-cisplatin ( CDDP ) regimen in patients with locally advanced unresectable poor prognosis stage IIIB or metastatic stage IV non-small cell lung cancer . The primary endpoints were overall survival ( OS ) and analysis of toxicity , while secondary endpoints included response rates , time-to-progression ( TTP ) and quality of life ( QoL ) . PATIENTS AND METHODS Eligible patients were r and omized to receive : ( a ) VNR 25mg/m(2 ) on day 1 , 8 and 15 plus CDDP 100mg/m(2 ) on day 1 every 4 weeks or ( b ) VNR 30 mg/m(2 ) on day 1 and 8 plus CDDP 80 mg/m(2 ) on day 1 every 3 weeks . All patients were chemotherapy-naïve and had an ECOG performance status ( PS ) of 0 - 1 . RESULTS Overall 278 patients were enrolled into the trial . Overall response rate was 34 % ( 95 % CL 26 - 42 % ) in the weekly VNR/CDDP arm , and 32 % ( 95 % CL 24 - 40 % ) in patients treated with day 1 - 8 VNR/CDDP without any statistically significant difference . Median TTP was 4.5 and 4.6 months respectively for weekly VNR/CDDP arm and the day 1 - 8 VNR/CDDP one . This difference was not statistically significant ( log-rank test , p=0.818 ) . Median OS was 9.45 and 10 months respectively for weekly VNR/CDDP arm and the day 1 - 8 VNR/CDDP one without statistically a significant difference ( log-rank test , p=0.259 ) . The 1- and 2-year survival rates were 31 and 36 % , and 10 and 11 % respectively . The incidence of severe neutropenia ( 34 % versus 68 % ; p=0.0001 ) and of febrile neutropenia ( 5 % versus 12 % ; p=0.026 ) , as well as the rate of therapy omissions ( 10 % versus 24 % ; p=0.0037 ) were higher in the weekly VNR/CDDP arm than in the day 1 - 8 VNR/CDDP one . The weekly VNR/CDDP regimen was associated with a lower received dose intensity in a statistically significant fashion ( 9 % versus 22 % ; p=0.0001 ) and with a lower non-statistically significant quality of life score as compared to the day 1 - 8 VNR/CDDP schedule . CONCLUSIONS The combination of day 1 - 8 VNR plus CDDP every 3 weeks is less toxic and better tolerated than the regimen of weekly VNR plus CDDP every 4 weeks . The two schedules are equivalent in terms of overall response rate , median time-to-progression and overall survival . The combination of VNR on day 1 - 8 plus CDDP every 3 weeks may be considered as a reference regimen for the treatment of patients with advanced disease and those who deserve a postoperative therapy , and for future studies BACKGROUND A combination of chemotherapy and radiotherapy is the treatment base for locally advanced non-small cell lung cancer ( NSCLC ) . However , both loco-regional and distant failure is frequent . Attempts to improve the loco-regional control were made in three separate phase II studies in Swedish University Hospitals , where accelerated radiotherapy or concurrent daily or weekly chemotherapy with conventional radiotherapy were tested . Comparatively good results from these studies lead to this national r and omized phase II study , the RAKET- study , where the different concepts were investigated on a wider basis for further phase III studies . METHODS Inoperable stage III non-small cell lung cancer patients in good performance status ( PS<2 ) were equally r and omized to either of three arms in eight institutions . All arms started with two cycles of induction chemotherapy : paclitaxel 200 mg/m2 and carboplatin AUC6 . Arm A : a third identical cycle was given concomitant with start of accelerated radiotherapy , 1.7 Gy BID to 64.6 Gy in 4.5 weeks . Arm B consisted of daily concomitant paclitaxel 12 mg/m2 with conventionally fractionated radiotherapy : 2 Gy to 60 Gy in 6 weeks . Arm C : weekly concomitant paclitaxel 60 mg/m2 and identical radiotherapy to 60 Gy . Primary endpoint : TTP . Secondary : OS , toxicity , QL and relapse pattern . RESULTS Between June 2002 and May 2005 152 patients were r and omized and of them 151 were evaluable : 78 men and 73 women , median age 62 years ( 43 - 78 ) , 55 % had performance status 0 and 45 % PS 1 . Thirty-four percent had stage IIIa and 66 % IIIb . HISTOLOGY adenocarcinoma 48 % , squamous cell carcinoma 32 % and 20 % non-small cell carcinoma . The three arms were well balanced . Toxicity was manageable with 12 % grade s 3 - 4 esophagitis , 1 % grade s 3 - 4 pneumonitis and there was no clear difference between the arms . The QL data did not differ either . Median time to progression was 9.8 ( 8.3 - 12.7 ) months ( 8.8 , 10.3 and 9.3 months for arms A , B and C , respectively ) . Median survival was 17.8 ( 14.4 - 23.7 ) months ( 17.7 , 17.7 and 20.6 months for A , B and C , respectively ) . The 1- , 3- and 5-year overall survival was 63 , 31 and 24 % . Sixty-nine percent of the patients relapsed with distant metastases initially and 31 % had loco-regional tumor progression , without significant differences between treatment arms . Thirty-four percent developed brain metastases . CONCLUSIONS Treatment results are quite equal by intensifying the loco-regional treatment either by accelerated fractionated radiotherapy or daily or weekly concomitant chemo-radiotherapy both in terms of survival , toxicity and quality of life . The optimal treatment schedule for patients with locally advanced NSCLC is still to be decided and investigated in future clinical studies . Relapse pattern with distant metastases and especially brain metastases is a great problem and need further research for better therapy options and higher cure rate for this patient group PURPOSE Docetaxel has shown activity in elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . This r and omized phase III trial evaluated the efficacy and safety of docetaxel versus vinorelbine ( the current st and ard treatment ) in elderly patients . PATIENTS AND METHODS Chemotherapy-naïve patients age 70 years or older with stage IIIB/IV NSCLC and performance status 2 or lower were eligible . Patients r and omly received docetaxel 60 mg/m2 ( day 1 ) or vinorelbine 25 mg/m2 ( days 1 and 8) every 21 days for four cycles . The primary end point was overall survival . Overall disease-related symptom improvement was assessed using an eight-item question naire . RESULTS In total , 182 patients were enrolled . Median age was 76 years ( range , 70 years to 86 years ) . There was no statistical difference in median overall survival with docetaxel versus vinorelbine ( 14.3 months v 9.9 months ; hazard ratio , 0.780 ; 95 % CI , 0.561 to 1.085 ; P = .138 ) . There was a significant difference in median progression-free survival ( 5.5 months v 3.1 months ; P < .001 ) . Response rates were also significantly improved with docetaxel versus vinorelbine ( 22.7 % v 9.9 % ; P = .019 ) . The most common grade 3 to 4 toxicities were neutropenia ( 82.9 % for docetaxel ; 69.2 % for vinorelbine ; P = .031 ) and leukopenia ( 58.0 % for docetaxel ; 51.7 % for vinorelbine ) . Other toxicities were mild and generally well tolerated . Docetaxel improved overall disease-related symptoms over vinorelbine ( odds ratio , 1.86 ; 95 % CI , 1.09 to 3.20 ) . CONCLUSION Docetaxel improved progression-free survival , response rate , and disease-related symptoms versus vinorelbine . Overall survival was not statistically significantly improved at this time . Docetaxel monotherapy may be considered as an option in the st and ard treatment of elderly patients with advanced NSCLC PURPOSE This r and omized phase III trial of advanced or metastatic non-small-cell lung cancer ( NSCLC ) was design ed to compare a st and ard treatment such as carboplatin (CRP)-paclitaxel ( PCT ) with a new combination , vinorelbine (VRL)-PCT-two agents acting in microtubules . PATIENTS AND METHODS Three hundred and sixty patients ( stage IIIa , IIIb and IV ) were included and evaluated for response rate , survival and toxicity . Arm A patients were treated with the control combination of CRP 6 AUC and PCT 175 mg/m(2 ) repeated every 3 weeks for six cycles , and arm B with the investigational combination of VRL 25 mg/m(2 ) and PCT 135 mg/m(2 ) repeated every 2 weeks for nine cycles . The patients were well balanced with respect to gender , disease stage and performance status . Arm A received 849 cycles ( mean 4.59 per patient ) and arm B 951 cycles ( mean 5.39 per patient ) . RESULTS Complete and partial response rates were 45.95 % and 42.86 % for arms A and B , respectively . Median survival was 11 and 10 months , 1-year survival 42.7 % and 37.85 % and 2-year survival 10.12 % and 19 % for arms A and B , respectively . Toxicity was similar in all patients , except for neutropenia , which was significantly greater in arm B. CONCLUSIONS PCT combined with VRL produces similar ( non-significant ) response rates , survival and toxicity ( except for neutropenia , as noted above ) to st and ard CRP-PCT treatment in untreated advanced-stage NSCLC PURPOSE The purpose of this study is to analyze changes in quality of life ( QOL ) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III r and omized study ( Radiation Therapy Oncology Group 9801 ) of amifostine ( AM ) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy ( RT ) . METHODS AND MATERIAL S One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed . There were no significant differences in baseline demographics between those who did and did not have QOL data . The QOL and symptoms were assessed by using the European Organization for Research and Treatment of Cancer ( EORTC ) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool . Clinical ly relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment . A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log ( using National Cancer Institute Common Toxicity Criteria ) were completed during treatment . Weight loss was monitored . Differences in outcomes were examined according to smoking status , alcohol use , and sex . RESULTS Patients receiving AM reported significantly greater pain reduction after chemoradiation ( 34 % vs. no AM , 21 % ) , less difficulty swallowing during chemoradiation , and less weight loss than patients not receiving AM . However , physician-rated assessment s of dysphagia were not significantly different by treatment arm . There were no other significant changes in QOL or symptoms according to treatment arm , smoking status , alcohol use , or sex . CONCLUSIONS Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessment PURPOSE Adjuvant chemotherapy for early stage non-small-cell lung cancer ( NSCLC ) is now the st and ard of care , but there is little information regarding its impact on quality of life ( QOL ) . We report the QOL results of JBR.10 , a North American , intergroup , r and omized trial of adjuvant cisplatin and vinorelbine compared with observation in patients who have completely resected , stages IB to II NSCLC . PATIENTS AND METHODS QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and a trial-specific checklist at baseline and at weeks 5 and 9 for those who received chemotherapy and at follow-up months 3 , 6 , 9 , 12 , 18 , 24 , 30 and 36 . A 10-point change in QOL scores from baseline was considered clinical ly significant . RESULTS Four hundred eighty-two patients were r and omly assigned on JBR.10 . A total of 173 patients ( 82 % of the expected ) in the observation arm and 186 ( 85 % of expected ) in the chemotherapy arm completed baseline QOL assessment s. The two groups were comparable , with low global QOL scores and significant symptom burden , especially pain and fatigue , after thoracotomy . Changes in QOL during chemotherapy were relatively modest ; fatigue , nausea , and vomiting worsened , but there was a reduction in pain and no change in global QOL . Patients in the observation arm showed considerable improvements in QOL by 3 months . QOL , except for symptoms of sensory neuropathy and hearing loss , in those treated with chemotherapy returned to baseline by 9 months . CONCLUSION The findings of this trial indicate that the negative effects of adjuvant chemotherapy on QOL appear to be temporary , and that improvements ( with a return to baseline function ) are likely in most patients PURPOSE A multicenter r and omized phase II trial to evaluate two treatment strategies in the first-line management of advanced non-small-cell lung cancer ( NSCLC ) patients with a performance status ( PS ) of 2 . PATIENTS AND METHODS Patients were assigned to erlotinib 150 mg orally daily until progression or to carboplatin ( area under the curve [ AUC ] 6 ) and paclitaxel ( 200 mg/m(2 ) day 1 every 3 weeks ) for up to four cycles . Patients who experienced progression or did not tolerate or refused further chemotherapy were allowed to cross over to erlotinib . The primary end point was progression-free survival ( PFS ) . Secondary end points were response , survival , quality of life ( QOL ) , and a retrospective molecular correlation . RESULTS Fifty-two patients were r and omly assigned to erlotinib and 51 to chemotherapy . Partial responses were 2 % and 12 % , respectively . Median PFS was 1.9 months in the erlotinib arm and 3.5 months in the chemotherapy arm ( hazard ratio [ HR ] = 1.45 ; 95 % CI , 0.98 to 2.15 ; P = .06 ) . Median survival times were 6.5 and 9.7 months , respectively ( HR = 1.73 ; 95 % CI , 1.09 to 2.73 ; P = .018 ) . Patients who crossed over to erlotinib had a median survival of 14.9 months . Sex , histology , skin rash , and smoking history predicted outcome with erlotinib . Rash and diarrhea were more common with erlotinib ; emesis , alopecia , peripheral neuropathy , and fatigue were more common with chemotherapy . QOL was similar between the two arms . Molecular correlation was limited by available sample s. CONCLUSION Unselected patients with advanced NSCLC and PS 2 are best treated with combination chemotherapy as first-line therapy . Erlotinib may be considered in patients selected by clinical or molecular markers PURPOSE Gefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase . We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Chemotherapy-naïve patients with advanced stage ( IIIB/IV ) NSCLC , Eastern Cooperative Oncology Group performance status of 0 to 1 , and adequate organ function were r and omly assigned to either platinum-doublet chemotherapy up to six cycles ( arm A ) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily , until disease progression ( arm B ) . Patients were stratified by disease stage , sex , histology , and chemotherapy regimens . The primary end point was overall survival ; secondary end points included progression-free survival , tumor response , safety , and quality of life . Results Between March 2003 and May 2005 , 604 patients were r and omly assigned . There was a statistically significant improvement in progression-free survival in arm B ( hazard ratio [ HR ] , 0.68 ; 95 % CI , 0.57 to 0.80 ; P < .001 ) ; however , overall survival results did not reach statistical significance ( HR , 0.86 ; 95 % CI , 0.72 to 1.03 ; P = .11 ) . In an exploratory subset analysis of overall survival by histologic group , patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma ( n = 467 ; HR , 0.79 ; 95 % CI , 0.65 to 0.98 ; P = .03 ) . CONCLUSION This trial failed to meet the primary end point of OS in patients with NSCLC . The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib , especially for patients with adenocarcinoma |
2,349 | 22,030,293 | Even though advanced noncancer syndromes differ clinical ly , a universal set of prognostic factors signals progression to terminal disease , including poor performance status , advanced age , malnutrition , comorbid illness , organ dysfunction , and hospitalization for acute decompensation .
Generally , a 6-month median survival is associated with the presence of 2 - 4 of these factors .
With few exceptions , these terminal presentations are quite refractory to treatment .
There is little evidence at present that treatment prolongs survival at these terminal stages | PURPOSE We report on clinical indicators of 6-month mortality in advanced noncancer illnesses and the effect of treatment on survival . | UNLABELLED Both nadolol and ligation have proved to be effective in the prophylaxis of first variceal bleeding . This study was conducted to evaluate the effects and safety of combining nadolol with ligation . Cirrhotic patients with high-risk esophageal varices but without a bleeding history were considered for enrolment . Eligible patients were r and omized to receive b and ligation plus nadolol ( Combined group , 70 patients ) or nadolol alone ( Nadolol group , 70 patients ) . In the Combined group multiligators were applied . Patients received regular ligation treatment at an interval of 4 weeks until variceal obliteration . Nadolol was administered at a dose to reduce 25 % of the pulse rate in both the Combined group and the Nadolol group . Both groups were comparable in baseline data . In the Combined group 50 patients ( 71 % ) achieved variceal obliteration . The mean dose of nadolol was 52 + /- 16 mg in the Combined group and 56 + /- 19 mg in the Nadolol group . During a median follow-up of 26 months , 18 patients ( 26 % ) in the Combined group and 13 patients ( 18 % ) in the Nadolol group experienced upper gastrointestinal bleeding ( P = NS ) . Esophageal variceal bleeding occurred in 10 patients ( 14 % ) in the Combined group and nine patients ( 13 % ) in the Nadolol group ( P = NS ) . Adverse events were noted in 48 patients ( 68 % ) in the Combined group and 28 patients ( 40 % ) in the Nadolol group ( P = 0.06 ) . Sixteen patients in each group died . CONCLUSION The addition of ligation to nadolol may increase adverse events and did not enhance effectiveness in the prophylaxis of first variceal bleeding OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy . BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure ( HF ) , but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking . METHODS A total of 114 dialysis patients with dilated cardiomyopathy were r and omized to receive either carvedilol or placebo in addition to st and ard therapy . A first analysis was performed at one year and was followed by an additional follow-up period of 12 months . RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling , with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group . At two years , 51.7 % of the patients died in the carvedilol group , compared with 73.2 % in the placebo group ( p < 0.01 ) . Furthermore , there were significantly fewer cardiovascular deaths ( 29.3 % ) and hospital admissions ( 34.5 % ) among patients receiving carvedilol than among those receiving a placebo ( 67.9 % and 58.9 % , respectively ; p < 0.00001 ) . The exploratory analyses revealed that fatal myocardial infa rct ions , fatal strokes , and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group . A reduction in sudden deaths and pump-failure deaths was also observed , though it did not reach statistical significance . CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy . These data suggest the use of carvedilol in all dialysis patients with chronic HF Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) are not precisely understood . The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AE COPD . Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AE COPD were prospect ively assessed . Patients were followed-up for 3 yrs . Factors determining short- and long-term mortality were analysed . In total , 17 patients ( 8.3 % ) died in hospital . In-hospital mortality was significantly associated with lower arterial oxygen tension ( Pa , O2 ) , higher carbon dioxide arterial tension , lower arterial oxygen saturation and longer hospital stay . The overall 6-month mortality rate was 24 % , with 1- , 2- and 3-yr mortality rates of 33 % , 39 % and 49 % , respectively . Cox regression analysis revealed that long-term mortality was associated with longer disease duration ( relative risk ( RR ) = 1.158 ) , lower albumin ( RR = 0.411 ) , lower Pa , O2 ( RR = 0.871 ) and lower body mass index ( RR = 0.830 ) . When the model was run for the time elapsed since first hospitalisation , it also appeared as statistically significant ( RR = 1.195 ) . These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival . Prediction of survival status may be enhanced by considering arterial oxygen tension , albumin , body mass index , disease duration and time elapsed since the first hospitalisation CONTEXT Estimating life expectancy is challenging in advanced dementia , potentially limiting the use of hospice care in these patients . OBJECTIVE To prospect ively vali date and compare the performance of the Advanced Dementia Prognostic Tool ( ADEPT ) and hospice eligibility guidelines to estimate 6-month survival in nursing home residents with advanced dementia . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study conducted in 21 nursing homes in Boston , Massachusetts , of 606 residents with advanced dementia who were recruited between November 1 , 2007 , and July 30 , 2009 . Data were ascertained at baseline to determine the residents ' ADEPT score ( range , 1.0 - 32.5 ; higher scores indicate worse prognosis ) and whether they met Medicare hospice eligibility guidelines . Survival was followed up to 6 months . MAIN OUTCOME MEASURES Assessment and comparison of the performance of the ADEPT score and hospice guidelines to predict 6-month survival using sensitivity , specificity , and the area under the receiver operating characteristic ( AUROC ) curve . RESULTS At baseline , the residents ' mean ( SD ) ADEPT score was 10.1 ( 3.1 ) points and 65 residents ( 10.7 % ) met hospice eligibility guidelines . Over 6 months , 111 residents ( 18.3 % ) died . The AUROC for the ADEPT score 's prediction of 6-month mortality as a continuous variable was 0.67 ( 95 % confidence interval [ CI ] , 0.62 - 0.72 ) . The AUROC for Medicare hospice eligibility guidelines was 0.55 ( 95 % CI , 0.51 - 0.59 ) , the specificity was 0.89 ( 95 % CI , 0.86 - 0.92 ) , and the sensitivity was 0.20 ( 95 % CI , 0.13 - 0.28 ) . Using a cutoff of 13.5 on the ADEPT score , which also had specificity of 0.89 , the AUROC was 0.58 ( 95 % CI , 0.54 - 0.63 ) and the sensitivity was 0.27 ( 95 % CI , 0.19 - 0.36 ) . CONCLUSIONS When prospect ively vali date d at the bedside and used as a continuous measure , the ability of the ADEPT score to identify nursing home residents with advanced dementia at high risk of death within 6 months was modest , albeit better than hospice eligibility guidelines . Care provided to these residents should be guided by their goals of care rather than estimated life expectancy BACKGROUND Malnutrition is prevalent in elderly population s. Recommended methods of nutritional screening are often too complicated and time-consuming for routine application in frail , very old , hospitalized patients . OBJECTIVE Our aims were to identify risk factors for development of malnutrition in very old hospitalized patients and to evaluate the total Mini Nutritional Assessment ( MNA ) score and MNA subscores as predictors of in-hospital and long-term mortality . DESIGN A prospect i ve cohort study of patients aged > or = 75 y was conducted in a geriatric hospital . Assessment included demographic , clinical , and laboratory data and cognitive , functional , and nutritional status . Follow-up was conducted for < or = 2.7 y. RESULTS Of the 414 patients studied , only 73 ( 17.6 % ) were well-nourished . Low serum albumin and phosphorus concentrations , dementia , and cerebrovascular accident ( CVA ) were significant risk factors for malnutrition . Survival was significantly lower in malnourished patients and patients at risk of malnutrition than in well-nourished patients ( P < 0.0001 ) . Low MNA-3 subscores ( dietary habits ) were significantly correlated with laboratory indexes of malnutrition and were significantly lower in patients with infections , malignancy , pressure ulcers , dementia , recent orthopedic surgery , and CVA . Multivariate analysis showed that a low MNA-3 score was an independent predictor of mortality ; scores < 7.5 increased the risk of death 2.05-fold . CONCLUSIONS The prevalence of malnutrition was high in elderly hospitalized patients . Dietary habits were significant predictors of poor hospitalization outcome . A question naire on dietary habits can serve as a useful tool in assessing nutritional status and prognosis in elderly patients BACKGROUND / AIM Hepatorenal syndrome ( HRS ) is associated with a poor prognosis . The incidence and prognostic impact of kidney dysfunction due to other causes in cirrhotic patients are less well known . The current study prospect ively evaluated the incidence and the prognostic relevance of different etiologies of kidney failure in cirrhotic patients . METHODS Eighty-eight consecutive patients with cirrhosis and serum creatinine > or = 1.5 mg/dl were enrolled . The etiologies of kidney dysfunction were analyzed , and prognostic factors including Model for End-Stage Liver Disease ( MELD ) score were evaluated in a multivariate Cox model . RESULTS HRS was present in 35 ( 40 % ) patients ( 15 HRS 1 , 20 HRS 2 ) , followed by renal parenchymal disease ( 23 % ) , drug-induced kidney dysfunction ( 19 % ) and prerenal failure due to bleeding or infections ( 15 % ) . HRS patients had a significantly higher MELD score and shorter survival . In addition to the MELD score , only HRS 1 was independently predictive for survival . HRS 2 patients had a similar outcome as patients with non-HRS kidney dysfunction . CONCLUSIONS In patients with cirrhosis and renal failure , hepatorenal syndrome is associated with a worse prognosis than kidney dysfunction due to other conditions but only HRS type 1 has independent prognostic relevance in addition to the MELD score in these patients BACKGROUND A supplemented very-low-protein diet ( sVLPD ) seems to be safe when postponing dialysis therapy . STUDY DESIGN Prospect i ve multicenter r and omized controlled study design ed to assess the noninferiority of diet versus dialysis in 1-year mortality assessed by using intention-to-treat and per- protocol analysis . SETTING & PARTICIPANTS Italian uremic patients without diabetes older than 70 years with glomerular filtration rate of 5 to 7 mL/min ( 0.08 to 0.12 mL/s ) . INTERVENTION R and omization to an sVLPD ( diet group ) or dialysis . The sVLPD is a vegan diet ( 35 kcal ; proteins , 0.3 g/kg body weight daily ) supplemented with keto-analogues , amino acids , and vitamins . Patients following an sVLPD started dialysis therapy in the case of malnutrition , intractable fluid overload , hyperkalemia , or appearance of uremic symptoms . OUTCOMES & MEASUREMENTS Mortality , hospitalization , and metabolic markers . RESULTS 56 patients were r and omly assigned to each group , median follow-up was 26.5 months ( interquartile range , 40 ) , and patients in the diet group spent a median of 10.7 months ( interquartile range , 11 ) following an sVLPD . Forty patients in the diet group started dialysis treatment because of either fluid overload or hyperkalemia . There were 31 deaths ( 55 % ) in the dialysis group and 28 deaths ( 50 % ) in the diet group . One-year observed survival rates at intention to treat were 83.7 % ( 95 % confidence interval [ CI ] , 74.5 to 94.0 ) in the dialysis group versus 87.3 % ( 95 % CI , 78.9 to 96.5 ) in the diet group ( log-rank test for noninferiority , P < 0.001 ; for superiority , P = 0.6 ) : the difference in survival was -3.6 % ( 95 % CI , -17 to + 10 ; P = 0.002 ) . The hazard ratio for hospitalization was 1.50 for the dialysis group ( 95 % CI , 1.11 to 2.01 ; P < 0.01 ) . LIMITATIONS The unblinded nature of the study , exclusion of patients with diabetes , and incomplete enrollment . CONCLUSION An sVLPD was effective and safe when postponing dialysis treatment in elderly patients without diabetes Introduction . Non-dialytic treatment ( NDT ) has become a recognized and important modality of treatment in end stage renal disease ( ESRD ) in certain groups of chronic kidney disease ( CKD ) patients . However , little is known about the prognosis of these NDT patients in terms of hospitalization rates and survival . We analyzed our experience in managing these NDT with a multidisciplinary team ( MDT ) approach over a three-year period . Patients and Methods . The Renal Unit at the Royal Liverpool University Hospital set up a dedicated MDT clinic to manage NDT patients in January 2003 . Patients approaching end stage chronic kidney disease who chose not to dialyse were recruited from other nephrologists . The study group was classified according to age b and ( < 70 years , 71–80 years , and > 80 years ) , estimated glomerular filtration rate ( eGFR ) ( < 10 ml/min , 11–20 ml/min , and > 20 ml/min ) according to the Modified Diet In Renal Disease formula and Stoke comorbidity grade ( SCG ) . The SCG is a vali date d scoring system for the survival of patients on renal replacement therapy . We also used the ERA-EDTA primary renal diagnosis codes . As there are no existing st and ards for NDT patients , we used the U.K. national set for haemodialysis patients as a reference and target for our NDT patients . Data was collected prospect ively . Results . The median age was 79 years and the male : female ratio was approximately 1 . The most common primary cause of kidney disease in the NDT study population was chronic renal failure of unknown cause n = 22 ( 31 % ) , but the most common identifiable cause was diabetic nephropathy , n = 20 ( 28 % ) . The most common comorbidity was ischaemic heart disease n = 25 ( 34 % ) . Those achieving the st and ards for anaemia were 78 % at referral . Only 30 % of the NDT patients achieved the st and ard for blood pressure ( < 130/80 mmHg ) at referral . Forty-three patients ( 60 % ) had no admissions at all . There were a total of 30 patients admitted on 58 occasions . Thirty-one ( 53 % ) of these were due to a non-renal cause . The median length of stay for the other NDT patients was 10 days . The median overall survival ( life expectancy ) was 1.95 years . The one-year overall survival was 65 % . SCG was an independent prognostic factor in predicting survival in NDT patients studied ( p = 0.005 ) , the hazard ratio being 2.53 , for each incremental increase in the SCG . At one year , the survival for comorbidity grade 0 , 1 and 2 were 83 % , 70 % and 56 % respectively . Of the 28 patients who died , 20 did so at home ( 71 % ) . Discussion . The NDT of ESRD has become an important alternative modality in renal replacement therapy . With the emergence of epidemic proportions of CKD , more elderly patients with progressive renal disease will need to make informed decisions regarding renal replacement therapy . There is likely to be increasing number of elderly patients that will tolerate dialysis badly and who will be very dependent on others . We believe that there should be a multidisciplinary approach to assist the ESRD patients in choosing their modality of renal replacement therapy , and with an agreed care plan to support these patients in managing their chosen modality to achieve the best possible quality of life . There should be integrated services with primary care , community nurses , and palliative care teams to enable the majority of the patient 's treatment to be carried out at home and to allow a dignified death . However . there was a statistically significant trend for shorter survival among those with greater comorbidities , as determined by the SCG . This is the first report of the potential importance of SCG as an independent prognostic factor in NDT patients . This will help us to counsel our patients in the future about their prognosis if they choose NDT as their modality of renal replacement therapy . Conclusion . Our prospect i ve study is the first and currently the largest observational study of a multidisciplinary approach in the management of NDT patients . SCG was an independent prognostic factor in predicting survival . In those patients who chose not to dialyse , SCG provides a potentially useful indication of expected prognosis BACKGROUND AND AIMS The hepatopulmonary syndrome ( HPS ) has been defined by chronic liver disease , arterial deoxygenation , and widespread intrapulmonary vasodilation . Mortality of patients with HPS is considered to be high , but the effect of HPS on survival in patients with cirrhosis remains unclear . METHODS A total of 111 patients with cirrhosis were studied prospect ively by using transthoracic contrast echocardiography for detection of pulmonary vasodilation , blood gas analysis , and pulmonary function test . Twenty different clinical characteristics and survival times were noted . RESULTS Twenty-seven patients ( 24 % ) had HPS . Their mortality was significantly higher ( median survival , 10.6 months ) compared with patients without HPS ( 40.8 mo , P < 0.05 ) , even after adjusting for liver disease severity ( 2.9 vs. 14.7 months in Child-Pugh class C with [ n = 15 ] and without HPS [ n = 35 , P < 0.05 ] ; 35.3 vs. 44.5 months in Child-Pugh class B with [ n = 7 ] and without HPS [ n = 23 , P = NS ] ) , and exclusion of patients who underwent liver transplantation during follow-up ( median survival 4.8 vs. 35.2 months , P = 0.005 ) . Causes of death were mainly nonpulmonary and liver-related in the 19 patients with and the 35 patients without HPS who died . In multivariate analysis , HPS was an independent predictor of survival besides age , Child-Pugh class , and blood urea nitrogen . Mortality correlates with severity of HPS . CONCLUSIONS The presence of HPS independently worsens prognosis of patients with cirrhosis . This should influence patient management and scoring systems and accelerate the evaluation process for liver transplantation OBJECTIVES Identifying high-risk heart failure ( HF ) patients at hospital discharge may allow more effective triage to management strategies . BACKGROUND Heart failure severity at presentation predicts outcomes , but the prognostic importance of clinical status changes due to interventions is less well described . METHODS Predictive models using variables obtained during hospitalization were created using data from the ESCAPE ( Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness ) trial and internally vali date d by the bootstrapping method . Model coefficients were converted to an additive risk score . Additionally , data from FIRST ( Flolan International R and omized Survival Trial ) was used to externally vali date this model . RESULTS Patients discharged with complete data ( n = 423 ) had 6-month mortality and death and rehospitalization rates of 18.7 % and 64 % , respectively . Discharge risk factors for mortality included BNP , per doubling ( hazard ratio [ HR ] : 1.42 , 95 % confidence interval [ CI ] : 1.15 to 1.75 ) , cardiopulmonary resuscitation or mechanical ventilation during hospitalization ( HR : 2.54 , 95 % CI : 1.12 to 5.78 ) , blood urea nitrogen , per 20-U increase ( HR : 1.22 , 95 % CI : 0.96 to 1.55 ) , serum sodium , per unit increase ( HR : 0.93 , 95 % CI : 0.87 to 0.99 ) , age > 70 years ( HR : 1.05 , 95 % CI : 0.51 to 2.17 ) , daily loop diuretic , furosemide equivalents > 240 mg ( HR : 1.49 , 95 % CI : 0.68 to 3.26 ) , lack of beta-blocker ( HR : 1.28 , 95 % CI : 0.68 to 2.41 ) , and 6-min walk , per 100-foot increase ( HR : 0.955 , 95 % CI : 0.99 to 1.00 ; c-index 0.76 ) . A simplified discharge score discriminated mortality risk from 5 % ( score = 0 ) to 94 % ( score = 8) . Bootstrap validation demonstrated good internal validation of the model ( c-index 0.78 , 95 % CI : 0.68 to 0.83 ) . CONCLUSIONS The ESCAPE study discharge risk model and score refine risk assessment after in-hospital therapy for advanced decompensated systolic HF , allowing clinicians to focus surveillance and triage for early life-saving interventions in this high-risk population . ( Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ ESCAPE ] ; NCT00000619 ) BACKGROUND The change in the demographics and the presence of multiple risk factors and co-morbidities in UK patients starting dialysis may lead to poor survival on dialysis . Many of these risk factors are present in the pre-dialysis period allowing a potential window of opportunity to intervene with risk modification measures . AIM To examine various potential factors that may predict early and overall mortality . DESIGN AND METHODS We carried out an observational prospect i ve study of a cohort of incident patients starting dialysis in a UK centre . Univariate analysis of factors and co-morbidities potentially affecting survival on dialysis were analysed to potential predictors . Factors affecting 1 year mortality were analysed using the t-test , the Mann-Whitney U-test or the chi-square test as appropriate . Mortality over the 5-year follow-up period was analysed using the Kaplan-Meier method . RESULTS Ninety-four patients [ predominantly Caucasian ( 98 % ) ] , of mean age 63 years ( 15.6 ) ( 56 % > 65 years ) with a slight male preponderance were studied . Vascular disease ( 39 % ) and sepsis ( 33 % ) accounted for most of the deaths and a significant proportion of mortality was seen in the first year ( 56 % ) . Patients with early mortality were older ( 68 vs. 61 years , P = 0.05 ) with lower haemoglobin ( 8.4 vs. 9.4 g/dl , P = 0.01 ) at the start of dialysis , commenced dialysis with a lower eGFR ( 5.4 vs. 6.5 ml/min/1.73 m(2 ) , P = 0.06 ) and had more peripheral vascular disease ( PVD ) ( 39 % mortality in patients with PVD vs. 18.5 % in those without PVD , P = 0.04 ) . Diabetes mellitus , high calcium phosphate product , older age and presence of vascular co-morbidities including ischaemic heart disease and peripheral vascular disease were associated with overall mortality over the 5-year follow-up period . SUMMARY In this study , elevated calcium phosphate product and diabetes mellitus in addition to the presence of vascular disease were associated with poor survival . Patients with low haemoglobin and lower first pre-dialysis eGFR suffered higher early mortality . These potentially modifiable factors that could be identified in the pre-dialysis stage provide a valuable opportunity for intervention OBJECTIVE This hospital-based prospect i ve study tests the hypothesis that , in a large group of hospitalized elderly patients , those who report functional decline between pre-illness baseline and hospital admission have a higher risk of death . METHODS Nine hundred fifty elderly ambulant patients ( F = 69.3 % ; mean age 78.3 + /- 8.5 years ) were consecutively admitted to a geriatric ward ( Poliambulanza Hospital , Brescia , Italy ) during a 15-month period . Number and severity of somatic diseases , Charlson Index score , APACHE II score , level of serum albumin , cognitive status ( by Mini-Mental State Examination ) , and depression score ( by Geriatric Depression Scale ) , were assessed on admission and evaluated as potential prognostic factors . Functional status ( by Barthel Index ) was assessed by self-report on admission . Preadmission function was also assessed by self-report at the time of admission . Impairment of function due to an acute event is measured as the difference between performances on admission and 2 weeks before the acute event . Six-month survival was the main outcome variable . RESULTS Factors related to mortality in bivariate analysis were : male sex , age over 80 , cancer , congestive heart failure , pulmonary diseases , elevated Charlson Index score , and ( independently ) dementia ( Mini-Mental State Examination < 18 ) , APACHE-Acute Physiology Score , albumin level < 3.5 g/dL , and anemia . After controlling for these variables and for Barthel Index score 2 weeks before the acute event , change in function due to the acute disease is independently related to 6-month mortality ( minor functional change [ < 30 Barthel Index Point ] relative risk : 1.3 , 95 % confidence interval , 0.6 - 3.0 and major functional change [ major functional decrement ] relative risk : 2.8 , 95 % confidence interval , 1.3 - 5.7 ) . CONCLUSIONS Disease-induced disability may reflect a condition of biological inability to react to acute diseases ( i.e. , frailty ) , and should be assessed as a relevant prognostic indicator OBJECTIVES To identify variables associated with mortality in patients admitted to the hospital for acute exacerbation of COPD . DESIGN Prospect i ve cohort study . SETTING Acute-care hospital in Barcelona ( Spain ) . PATIENTS One hundred thirty-five consecutive patients hospitalized for acute exacerbation of COPD , between October 1996 and May 1997 . MEASUREMENTS AND RESULTS Clinical , spirometric , and gasometric variables were evaluated at the time of inclusion in the study . Socioeconomic characteristics , comorbidity , dyspnea , functional status , depression , and quality of life were analyzed . Mortality at 180 days , 1 year , and 2 years was 13.4 % , 22 % , and 35.6 % , respectively . Sixty-four patients ( 47.4 % ) were dead at the end of the study ( median follow-up duration , 838 days ) . Greater mortality was observed in the bivariate analysis among the oldest patients ( p < 0.0001 ) , women ( p < 0.01 ) , and unmarried patients ( p < 0.002 ) . Hospital admission during the previous year ( p < 0.001 ) , functional dependence ( Katz index ) [ p < 0.0004 ] , greater comorbidity ( Charlson index ) [ p < 0.0006 ] , depression ( Yesavage Scale ) [ p < 0.00001 ] ) , quality of life ( St. George 's Respiratory Question naire [ SGRQ ] ) [ p < 0.01 ] , and PCO(2 ) at discharge ( p < 0.03 ) were also among the significant predictors of mortality . In the multivariate analysis , the activity SGRQ subscale ( p < 0.001 ; odds ratio [ OR ] , 2.62 ; confidence interval [ CI ] , 1.43 to 4.78 ) , comorbidity ( p < 0.005 ; OR , 2.2 ; CI , 1.26 to 3.84 ) , depression ( p < 0.004 ; OR , 3.6 ; CI , 1.5 to 8.65 ) , hospital readmission ( p < 0.03 ; OR , 1.85 ; CI , 1.26 to 3.84 ) , and marital status ( p < 0.0002 ; OR , 3.12 ; CI , 1.73 to 5.63 ) were independent predictors of mortality . CONCLUSIONS Quality of life , marital status , depressive symptoms , comorbidity , and prior hospital admission provide relevant information of prognosis in this group of COPD patients BACKGROUND It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease ( ESRD ) . METHODS Using a national registry of patients undergoing dialysis , which was linked to a national registry of nursing home residents , we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis . Functional status was measured by assessing the degree of dependence in seven activities of daily living ( on the Minimum Data Set-Activities of Daily Living [ MDS-ADL ] scale of 0 to 28 points , with higher scores indicating greater functional difficulty ) . RESULTS The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis . Three months after the initiation of dialysis , functional status had been maintained in 39 % of nursing home residents , but by 12 months after the initiation of dialysis , 58 % had died and predialysis functional status had been maintained in only 13 % . In a r and om-effects model , the initiation of dialysis was associated with a sharp decline in functional status , indicated by an increase of 2.8 points in the MDS-ADL score ( 95 % confidence interval [ CI ] , 2.5 to 3.0 ) ; this decline was independent of age , sex , race , and functional-status trajectory before the initiation of dialysis . The decline in functional status associated with the initiation of dialysis remained substantial ( 1.7 points ; 95 % CI , 1.4 to 2.1 ) , even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis . CONCLUSIONS Among nursing home residents with ESRD , the initiation of dialysis is associated with a substantial and sustained decline in functional status BACKGROUND Health-related quality of life may affect morbidity and survival in end-stage renal disease , but it is not clear whether coexisting comorbidity and other known prognostic variables could account for such an association . METHODS To study the relationship between health-related quality of life and morbidity and survival , we carried out an inception cohort study in patients starting chronic dialysis , mostly diabetics , with a follow-up of 1 - 3 years in 34 Spanish hospitals . Health-related quality of life was measured by the SF-36 Health Survey and Karnofsky scale . Charlson age-comorbidity index and other prognostic clinical variables were measured concurrently . The primary outcome variable was time until death and the secondary outcome was hospitalization days . RESULTS Of 318 patients enrolled ( 208 diabetics ) , with a median follow-up of 771 days , 80 died . In the unadjusted analysis , all-cause mortality was associated with lower SF-36 physical and mental component scores and Karnofsky scale . In the adjusted analysis , SF-36 mental component score predicted all-cause mortality ( hazard ratio for a 10 point decrease : 1.28 ; 95 % confidence interval : 1.05 - 1.56 ) . The SF-36 mental component score also predicted more hospitalization days ( adjusted risk ratio of each additional hospital day associated with every 10 point decrease : 1.25 ; 95 % confidence interval : 1.08 - 1.45 ) . Among diabetics , both the SF-36 physical and mental components predicted mortality and hospitalization days . CONCLUSIONS In end-stage renal disease , perceived mental health is an independent predictor of mortality and morbidity , mainly among diabetics patients BACKGROUND Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure , but little is known about their effects in severe heart failure . METHODS We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion , who were clinical ly euvolemic , and who had an ejection fraction of less than 25 percent . In a double-blind fashion , we r and omly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months , during which st and ard therapy for heart failure was continued . Patients who required intensive care , had marked fluid retention , or were receiving intravenous vasodilators or positive inotropic drugs were excluded . RESULTS There were 190 deaths in the placebo group and 130 deaths in the carvedilol group . This difference reflected a 35 percent decrease in the risk of death with carvedilol ( 95 percent confidence interval , 19 to 48 percent ; P=0.00013 , unadjusted ; P=0.0014 , adjusted for interim analyses ) . A total of 507 patients died or were hospitalized in the placebo group , as compared with 425 in the carvedilol group . This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol ( 95 percent confidence interval , 13 to 33 percent ; P<0.001 ) . The favorable effects on both end points were seen consistently in all the subgroups we examined , including patients with a history of recent or recurrent cardiac decompensation . Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons ( P=0.02 ) . CONCLUSIONS The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial Objectives : The aim of the study was , by early identification of deleterious prognostic factors that are open to remediation , to be in a position to assign elderly patients to different mortality risk groups to improve management . Design : Prospect i ve multicentre cohort . Setting : Nine French teaching hospitals . Participants : One thous and three hundred and six ( 1 306 ) patients aged 75 and over , hospitalised after having passed through Emergency Department ( ED ) . Measurements : Patients were assessed using Comprehensive Geriatric Assessment ( CGA ) tools . A Cox survival analysis was performed to identify prognostic variables for six-week mortality . Receiver Operating Characteristics analysis was used to study the discriminant power of the model . A mortality risk score is proposed to define three risk groups for six-week mortality . Results : Crude mortality rate after a six-week follow-up was 10.6 % ( n=135 ) . Prognostic factors identified were : malnutrition risk ( HR=2.1 ; 95 % CI : 1.1–3.8 ; p=.02 ) , delirium ( HR=1.7 ; 95 % CI : 1.2 - 2.5 ; p=.006 ) , and dependency : moderate dependency ( HR=4.9 ; 95 % CI : 1.5–16.5 ; p=.01 ) or severe dependency ( HR=10.3 ; 95 % CI : 3.2–33.1 ; p < .001 ) . The discriminant power of the model was good : the c-statistic representing the area under the curve was 0.71 ( 95 % IC : 0.67 – 0.75 ; p < .001 ) . The six-week mortality rate increased significantly ( p < .001 ) across the three risk groups : 1.1 % ( n=269 ; 95 % CI=0.5–1.7 ) in the lowest risk group , 11.1 % ( n=854 ; 95 % CI=9.4–12.9 ) in the intermediate risk group , and 22.4 % ( n=125 ; 95 % CI=20.1–24.7 ) in the highest risk group . Conclusions : A simple score has been calculated ( using only three variables from the CGA ) and a practical schedule proposed to characterise patients according to the degree of mortality risk . Each of these three variables ( malnutrition risk , delirium , and dependency ) identified as independent prognostic factors can lead to a targeted therapeutic option to prevent early mortality BACKGROUND AND AIM Terlipressin has been proposed to treat renal failure in patients with type 1 hepatorenal syndrome ( HRS ) . However , the predictive factors for improved renal function and survival are unknown in patients with type 1 HRS treated with terlipressin . The aim of the present retrospective study was to investigate the predictive factors and prognosis of patients with type 1 HRS treated with terlipressin . METHODS The clinical charts of 18 consecutive patients with cirrhosis and type 1 HRS treated with terlipressin were studied . The predictive factors for improved renal function and survival were identified using univariate analyses . RESULTS Improved renal function , indicated by a significant decrease in serum creatinine ( 61 + /- 4 % ) , occurred in 11 ( 60 % ) patients . The only predictive factor for improved renal function was a Child-Pugh 's score < or = 13 at the time of diagnosis of HRS ( P = 0.02 ) . Fifteen patients ( 83 % ) died at 45 days and the median survival was 24 days . Of the three patients who survived , two underwent successful orthotopic liver transplantation . Three predictive factors for survival were identified : absence of a precipitating factor for HRS ( P = 0.012 ) ; improved renal function during terlipressin therapy ( P = 0.05 ) ; and a dose of terlipressin > or =3 mg/day ( P = 0.04 ) . CONCLUSIONS In patients with type 1 HRS treated with terlipressin , patients with improved renal function had less severe cirrhosis ( Child-Pugh > 10 but < or = 13 ) than patients without . The predictive factors for survival were the absence of a precipitating factor for HRS , the terlipressin-induced improvement in renal function and a dose of terlipressin of at least 3 mg/day . These findings suggest that a r and omized controlled trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed Background / Aims : Given the clear benefits of mortality reduction observed for most β-blockers in clinical trials , they are relatively underused in hemodialysis patients . Since the outcomes associated with the use of β-blockers are not fully known , we investigated their effect on mortality among a cohort of hemodialysis patients . Methods : Data were analyzed from the Dialysis Outcomes and Practice Patterns Study phase II for 2,286 r and omly selected patients on hemodialysis in Japan . Treatment with β-blockers was the major predictor variable . The main outcome measure was all-cause mortality . Cox regression analysis was used to assess an association between treatment with β-blockers and the risk of death . Results : 247 patients ( 11.9 % ) were administered β-blockers and 1,828 patients ( 88.1 % ) were not . Whereas patients treated with β-blockers had a higher prevalence of hypertension and coronary heart disease , Kaplan-Meier analysis revealed that all-cause mortality rates were significantly ( p < 0.007 ) decreased in patients treated with β-blockers compared to those without . In multivariable , fully adjusted models , treatment with β-blockers was also independently associated with reduced all-cause mortality ( hazard ratio = 0.48 ; p = 0.02 ) . Conclusion : This study indicated a possible association between the use of β-blockers and reduced risk of mortality in hemodialysis patients . These results should be confirmed in further r and omized controlled trials BACKGROUND Evidence -based health policy is urgently needed to meet the increasing dem and for health services among elderly people , particularly for expensive technologies such as renal-replacement therapy . Age has been used to ration dialysis , although not always explicitly , despite the lack of rigorous empirical evidence about how elderly people fare on dialysis . We undertook a comprehensive assessment of outcomes in patients 70 years or over . METHODS We did a 12-month prospect i ve cohort study of outcomes in 221 patients with end-stage renal failure aged 70 years or over recruited from four hospital-based renal units . We assessed 1-year survival in 125 incident patients ( 70 - 86 years ) and disease burden ( hospital admissions , quality of life , costs ) in 174 prevalent patients ( 70 - 93 years ) . FINDINGS 1-year survival rates were : 71 % overall ; 80 % , 69 % , and 54 % in patients 70 - 74 years , 75 - 79 years , and 80 years and older , respectively ( p=0.008 ) ; and 88 % , 71 % , and 64 % in patients with no , one , or two or more comorbid conditions , respectively ( p=0.056 ) . Cox regression analyses showed that mortality was significantly associated with age 80 years and older ( relative risk 2.79 [ 95 % CI 1.28 - 6.93 ] ) and peripheral vascular disease ( 2.83 [ 1.29 - 6.17 ] ) , but not with diabetes , ischaemic heart disease , cerebrovascular disease , chronic obstructive airways disease , sex , or treatment method . In terms of disease burden , hospital admissions represent a low proportion of costs and was not required by a third of patients , mental quality of life in elderly dialysis patients was similar to that of elderly people in the general population , and the average annual cost per patient of 20802 ( US$ 31200 ) ( 68 % dialysis treatment , 1 % transport , 19 % inpatient hospital admissions , 12 % medications ) was within the range of other life-extending interventions . INTERPRETATION Our results suggest that age alone should not be used as a barrier to referral and treatment and emphasise the need to consider the benefits of dialysis in elderly people . Indicators of the ability to benefit from treatment , rather than chronological age , should be used to develop policies that ensure equal access to care for all BACKGROUND beta-Blockers have been shown to be beneficial in the treatment and prevention of heart failure ( HF ) in the general population , but they have not been assessed for their association with nonfatal HF in a nationally representative population of long-term dialysis patients . METHODS We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data System ( USRDS ) Wave 2 who were Medicare eligible at the start of the study . Analysis was stratified by the presence or absence of a known diagnosis of HF , and patients followed up until December 31 , 2000 . Cox regression analysis , including propensity scores , was used to model adjusted hazard ratios for beta-blocker use ( assessed separately by cardioselective activity and lipid solubility ) with time to the first Medicare institutional cl aim for HF , cardiovascular-related death , or death from any cause . RESULTS In patients without a previous history of HF , beta-blocker use was significantly associated with a lower adjusted risk of HF ( adjusted hazard ratio , 0.69 ; 95 % confidence interval , 0.52 - 0.91 ; P=.008 ) , with a similar reduction in risk of cardiac-related and all-cause death . beta-Blocker use had no statistically significant associations with outcomes in patients with previous HF . CONCLUSIONS In dialysis patients without a previous documented history of HF , beta-blocker use was associated with a lower risk of new HF , cardiovascular death , and death from any cause . No such associations were seen for dialysis patients with a previous history of HF . These results are hypothesis generating only and should be confirmed in r and omized trials OBJECTIVES To determine predictors of mortality in the intensive care unit ( ICU ) and at 6 months after discharge ; to assess the lifestyles of survivors 6 months after discharge . DESIGN Prospect i ve cohort study of patients screened upon admission and 6 months after discharge from the ICU . SETTING The ICU of a university hospital . PARTICIPANTS One hundred sixteen consecutive patients age 70 and older admitted to the ICU and treated by mechanical ventilation for at least 24 hours . MEASUREMENTS A comprehensive medical , functional , nutritional , and social assessment was undertaken for each patient upon admission to the ICU . Functional status and residence were recorded for patients still living 6 months after discharge from the ICU . RESULTS Mortality in the ICU and 6 months after discharge was 31 % and 52 % , respectively . The predictors of in-ICU mortality on multivariate analysis were a high omega score per day in the ICU and a high simplified acute physiologic score corrected for points related to age ( SAPS IIc ) . The predictors of mortality at 6 months were a high omega score per day in the ICU , a high SAPS IIc , and a mid-arm circumference ( MAC ) under the 10th percentile for the older French population in good health . Six months after discharge from the ICU , 91 % of the surviving patients had the same residential status and 89 % had a similar or improved functional status compared with pre-admission status . CONCLUSIONS Although severity of illness remains an important predictor of in-ICU mortality and mortality at 6 months after release from ICU , we found that impaired nutritional status upon admission was related to 6-month mortality . These results emphasize the need for a systematic nutritional assessment in older patients admitted to the ICU and treated by mechanical ventilation Objective : To study the mortality and quality of life ( QOL ) of survivors at 6 yrs after intensive care unit ( ICU ) admission for chronic obstructive pulmonary disease . Design : Prospect i ve , multiple-center cohort study . Setting : A total of 86 ICUs throughout Spain . Patients : Patients in the Project for the Epidemiological Analysis of Critical Care Patients ( PAEEC ) project with chronic obstructive pulmonary disease were included . Measurements and Main Results : The sample comprised 742 patients ; 508 of them were admitted for acute exacerbation of chronic obstructive pulmonary disease , and 379 of these required intermittent positive-pressure ventilation . The mean age of the patients was 65.2 ± 9.89 yrs , Acute Physiology and Chronic Health Evaluation ( APACHE ) III score was 66.6 ± 21.04 ; preadmission QOL question naire score was 7 ± 4.82 points , and hospital mortality was 31.8 % . At 6 yrs , 32.2 % had died after hospital discharge , 21.6 % could not be traced , and 107 patients were alive ( 18.3 % of the 582 followed-up patients ) . QOL of survivors was worse than preadmission ( 6.55 ± 5.6 vs. 4.92 ± 4.5 points , p < .05 ) , but 72 % of patients were self-sufficient . Among the 379 patients admitted to the ICU for acute chronic obstructive pulmonary disease exacerbation and requiring intermittent positive-pressure ventilation , 36.7 % died in the hospital ; at 6 yrs after hospital discharge , 31.4 % had died , 18.7 % could not be traced , and 50 patients ( 16.2 % of followed-up patients ) were alive . Multivariate analysis with logistic regression showed that the mortality at 6 yrs was related to age ( odds ratio , 1.046 ; 95 % confidence interval , 1.023–1.071 ) , APACHE III score ( odds ratio , 1.013 ; 95 % confidence interval , 1.001–1.024 ) , and preadmission QOL score ( odds ratio , 1.139 ; 95 % confidence interval , 1.078–1.204 ) . Conclusion : The 6-yr mortality of patients with chronic obstructive pulmonary disease requiring ICU admission is high . Mortality is mainly influenced by pre-ICU admission QOL . At 6 yrs , at least 15 % are alive ; survivors have a worse QOL compared with pre-ICU admission , although three quarters of them are self-sufficient OBJECTIVE To determine the association between functional and nutritional changes caused by an acute illness requiring hospitalisation and 6-month mortality . DESIGN Hospital-based prospect i ve longitudinal cohort study . SETTING Acute care centre ( Hospital General de Vic , Barcelona Province , Spain ) . Post-acute care centre ( Hospital de la Santa Creu de Vic , Barcelona Province , Spain ) . SUBJECTS Hundred sixty five patients aged 75 years and older , hospitalised for an acute event . METHODS Functional status ( Barthel and Lawton Indices ) , cognitive status ( Short Portable Mental Status Question naire ) , nutritional status ( Mini Nutritional Assessment , albumin , cholesterol ) , depressive symptoms ( Geriatric Depression Scale ) , co-morbidity ( Charlson Index ) and self-rated health status were collected upon admission to the post-acute care centre . Functional and nutritional status were assessed 1 , 3 and 6 months after admission by a trained staff of geriatricians . Six-month mortality was the main outcome variable . Survival analysis was performed with functional and nutritional status as time-dependent variables . RESULTS The mean age of the cohort was 83.3 years ( SD 5.1 ) and 68.5 % were female . Six-month mortality was 29.1 % ( 95 % CI : 22.2 - 36.7 ) . The variables associated with mortality in bivariate analysis were : gender , Barthel Index ( 2 weeks before admission ) , Lawton Index ( 2 weeks before admission ) , Charlson Index , Barthel Index ( time-dependent ) , Mini Nutritional Assessment ( MNA ) ( time-dependent ) and cognitive status . The variables associated with mortality in multivariate analysis were : gender , Barthel Index ( 2 weeks before admission ) , Charlson Index and MNA ( time-dependent ) . CONCLUSIONS Functional and nutritional changes due to an acute illness have a statistical and clinical prognostic value and should be assessed along with other well-known relevant prognostic factors The R and omized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure ( REMATCH ) trial demonstrated increased 1- and 2-year survival and improved quality of life for end-stage heart failure patients implanted with the HeartMate VE Left Ventricular Assist Device ( LVAD ) ( Thoratec Corporation , Pleasanton , CA ) compared with optimal medical management . This is the first report of Destination Therapy ( DT ) experience since REMATCH and incorporates improvements with the HeartMate XVE LVAD and patient management . Forty-two patients with end-stage heart failure at higher volume institutions were supported with the LVAD over a duration of 26.7 patient years ( mean 232 days ) . Compared with REMATCH , DT patients had a 40 % lower rate of death ( 0.49 vs. 0.84 deaths per patient year ) . Kaplan-Meier estimates of survival in the DT and REMATCH LVAD groups at 30 days were 90 % and 81 % , and at 1 year were 61 % and 52 % . The death rate due to sepsis was 8.3 times lower in DT patients ( risk ratio , 0.12 ; 95 % confidence interval , 0.02 - 0.90 ) . DT patients were 2.1 times less likely to experience an adverse event ( risk ratio , 0.47 ; 95 % confidence interval , 0.35 - 0.63 ) . These results demonstrate continued improvement with outcomes in long-term DT with LVADs . Given that these DT patients were similar to those in the REMATCH trial , the improved outcomes likely reflect improvements in the HeartMate XVE LVAD and experience with patient management Background and aims : Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic b and ligation ( EBL ) in the prevention of recurrent bleeding , but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate . The present study was aim ed at evaluating this issue in a multicentre r and omised controlled trial ( RCT ) and to correlate changes in hepatic venous pressure gradient ( HVPG ) during treatment with clinical outcomes Methods : 158 patients with cirrhosis , admitted because of variceal bleeding , were r and omised to receive nadolol+isosorbide-5-mononitrate alone ( Drug : n = 78 ) or combined with EBL ( Drug+EBL ; n = 80 ) . HVPG measurements were performed at r and omisation and after 4–6 weeks on medical therapy . Results : Median follow-up was 15 months . One-year probability of recurrent bleeding was similar in both groups ( 33 % vs 26 % : p = 0.3 ) . There were no significant differences in survival or need of rescue shunts . Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group . Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders ( HVPG reduction ⩾20 % or ⩽12 mm Hg ) . Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL . Conclusions : Adding EBL to pharmacological treatment did not reduce recurrent bleeding , the need for rescue therapy , or mortality , and was associated with more adverse events . Furthermore , associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders . IS RCT Ki and a MN , Wissing KM , Broeders NE , Lemy A , Ghisdal L , Hoang AD , Mikhalski D , Donckier V , Vereerstraeten P , Abramowicz D. In eligibility for renal transplantation : prevalence , causes and survival in a consecutive cohort of 445 patients . Clin Transplant 2011 : 25 : 576–583 . © 2010 John Wiley & Sons OBJECTIVES We sought to evaluate the influence of pretreatment systolic blood pressure ( SBP ) on the efficacy and safety of carvedilol in patients with chronic heart failure ( CHF ) . BACKGROUND Although beta-blockers reduce the risk of death in CHF , there is little reported experience with these drugs in patients with a low pretreatment SBP , who may respond poorly to beta-blockade . METHODS We studied 2,289 patients with severe CHF who participated in the Carvedilol Prospect i ve R and omized Cumulative Survival ( COPERNICUS ) trial . RESULTS Compared with placebo , carvedilol improved the clinical status and reduced the risk of death and the combined risk of death or hospitalization for any reason , for a cardiovascular reason , or for worsening heart failure ( p < 0.001 for all ) . The relative magnitude of these benefits did not vary as a function of the pretreatment SBP ( all interaction : p > 0.10 ) . However , because patients with the lowest SBP were at highest risk of an event , they experienced the greatest absolute benefit from treatment with carvedilol . The lower the pretreatment SBP , the more likely that patients would report an adverse event , be intolerant of high doses of the study drug , or require permanent withdrawal of treatment ( p < 0.001 for all ) . However , these risks were primarily related to the severity of the underlying illness and not to treatment with carvedilol . CONCLUSIONS The current study provides little support for concerns about using beta-blockers ( particularly those with vasodilatory actions ) in patients with severe CHF who have a low SBP . Pretreatment blood pressure can identify patients who have the greatest need for risk reduction with carvedilol BACKGROUND In clinical practice , there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease , with a worldwide trend toward early initiation . In this study , conducted at 32 centers in Australia and New Zeal and , we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease . METHODS We r and omly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate ( GFR ) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area ( calculated with the use of the Cockcroft-Gault equation ) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute ( early start ) or when the estimated GFR was 5.0 to 7.0 ml per minute ( late start ) . The primary outcome was death from any cause . RESULTS Between July 2000 and November 2008 , a total of 828 adults ( mean age , 60.4 years ; 542 men and 286 women ; 355 with diabetes ) underwent r and omization , with a median time to the initiation of dialysis of 1.80 months ( 95 % confidence interval [ CI ] , 1.60 to 2.23 ) in the early-start group and 7.40 months ( 95 % CI , 6.23 to 8.27 ) in the late-start group . A total of 75.9 % of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute , owing to the development of symptoms . During a median follow-up period of 3.59 years , 152 of 404 patients in the early-start group ( 37.6 % ) and 155 of 424 in the late-start group ( 36.6 % ) died ( hazard ratio with early initiation , 1.04 ; 95 % CI , 0.83 to 1.30 ; P=0.75 ) . There was no significant difference between the groups in the frequency of adverse events ( cardiovascular events , infections , or complications of dialysis ) . CONCLUSIONS In this study , planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes . ( Funded by the National Health and Medical Research Council of Australia and others ; Australian New Zeal and Clinical Trials Registry number , 12609000266268 . Increased portal pressure during variceal bleeding may have an influence on the treatment failure rate , as well as on short‐ and long‐term survival . However , the usefulness of hepatic hemodynamic measurement during the acute episode has not been prospect ively vali date d , and no information exists about the outcome of hemodynamically defined high‐risk patients treated with early portal decompression . Hepatic venous pressure gradient ( HVPG ) measurement was made within the first 24 hours after admission of 116 consecutive patients with cirrhosis with acute variceal bleeding treated with a single session of sclerotherapy injection during urgent endoscopy . Sixty‐four patients had an HVPG less than 20 mm Hg ( low‐risk [ LR ] group ) , and 52 patients had an HVPG greater than or equal to 20 mm Hg ( high‐risk [ HR ] group ) . HR patients were r and omly allocated into those receiving transjugular intrahepatic portosystemic shunt ( TIPS ; HR‐TIPS group , n = 26 ) within the first 24 hours after admission and those not receiving TIPS ( HR‐non‐TIPS group ) . The HR‐non‐TIPS group had more treatment failures ( 50 % vs. 12 % , P = .0001 ) , transfusional requirements ( 3.7 ± 2.7 vs. 2.2 ± 2.3 , P = .002 ) , need for intensive care ( 16 % vs. 3 % , P < .05 ) , and worse actuarial probability of survival than the LR group . Early TIPS placement reduced treatment failure ( 12 % , P = .003 ) , in‐hospital and 1‐year mortality ( 11 % and 31 % , respectively ; P < .05 ) . In conclusion , increased portal pressure estimated by early HVPG measurement is a main determinant of treatment failure and survival in variceal bleeding , and early TIPS placement reduces treatment failure and mortality in high risk patients defined by hemodynamic criteria . ( Hepatology 2004;40:793–801 ) BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk . However , a benefit of statins in such patients who are undergoing hemodialysis has not been proved . METHODS We conducted an international , multicenter , r and omized , double-blind , prospect i ve trial involving 2776 patients , 50 to 80 years of age , who were undergoing maintenance hemodialysis . We r and omly assigned patients to receive rosuvastatin , 10 mg daily , or placebo . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary end points included death from all causes and individual cardiac and vascular events . RESULTS After 3 months , the mean reduction in low-density lipoprotein ( LDL ) cholesterol levels was 43 % in patients receiving rosuvastatin , from a mean baseline level of 100 mg per deciliter ( 2.6 mmol per liter ) . During a median follow-up period of 3.8 years , 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point ( 9.2 and 9.5 events per 100 patient-years , respectively ; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group , 0.96 ; 95 % confidence interval [ CI ] , 0.84 to 1.11 ; P=0.59 ) . Rosuvastatin had no effect on individual components of the primary end point . There was also no significant effect on all-cause mortality ( 13.5 vs. 14.0 events per 100 patient-years ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.51 ) . CONCLUSIONS In patients undergoing hemodialysis , the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . ( Clinical Trials.gov number , NCT00240331 . BACKGROUND Delirium is a disorder affecting consciousness , which gives rise to core clinical features and associated symptoms . Older patients are particularly prone , owing to higher rates of pre-existing cognitive impairment , frailty , co-morbidity and polypharmacy . OBJECTIVES The aim of this study was to investigate the hypotheses that delirium affects the most vulnerable older adults and is associated with long-term adverse health outcome . METHODS This prospect i ve cohort study evaluated 278 medical patients aged > or = 75 years admitted acutely to a district general hospital in South Wales . Patients were screened for delirium at presentation and on alternate days throughout their hospital stay . Assessment s also included illness severity , preadmission cognition , co-morbidity and functional status . Patients were followed for 5 years to determine rates of institutionalisation and mortality . Number of days in hospital in the 4 years prior to and 5 years after index admission were recorded . RESULTS Delirium was detected in 103 patients and excluded in 175 . Median time to death was 162 days ( interquartile range 21 - 556 ) for those with delirium compared with 1,444 days ( 25 % mortality 435 days , 75 % mortality>5 years ) for those without ( P < 0.001 ) . After adjusting for multiple confounders , delirium was associated with an increased risk of death ( hazard ratio range 2.0 - 3.5 ; P < or = 0.002 ) . Institutionalisation was higher in the first year following delirium ( P = 0.03 ) . While those with delirium tended to be older with more preadmission cognitive impairment , greater functional dependency and more co-morbidity , they did not spend more days in hospital in the 4 years prior to index admission . CONCLUSIONS Delirium is associated with high rates of institutionalisation and an increased risk of death up to 5 years after index event . Prior to delirium , individuals seem to compensate for their vulnerability . The impact of delirium itself , directly or indirectly , may convert vulnerability into adverse outcome OBJECTIVES To identify predictors of 6-month mortality in older patients with heart failure ( HF ) and to develop a risk score for identifying potential c and i date s for hospice care . DESIGN Secondary data analysis of a previously conducted r and omized , clinical trial . SETTING Barnes-Jewish Hospital , St. Louis , Missouri . PARTICIPANTS Two hundred eighty-two patients with HF aged 70 and older . INTERVENTION Participants were r and omized to conventional care or a multidisciplinary intervention design ed to reduce rehospitalization . MEASUREMENTS All-cause 6-month mortality . RESULTS Patients were followed for up to 14 years ; 43 ( 15.2 % ) died within 6 months of hospital discharge . Multivariate logistic regression analysis identified four independent predictors of 6-month mortality : serum urea nitrogen of 30 mg/dL or greater ( odds ratio (OR)=5.78 , 95 % confidence interval (CI)=2.65 - 12.66 ) , systolic blood pressure less than 120 mmHg ( OR=4.81 , 95 % CI=1.94 - 11.91 ) , peripheral arterial disease ( OR=3.09 , 95 % CI=1.26 - 7.58 ) , and serum sodium less than 135 mEq/L ( OR=2.27 , 95 % CI=0.98 - 5.27 ) . Patients were stratified into four risk groups based on the presence or absence of these four risk factors . Six-month mortality rates for patients with zero , one , two , or three or more risk factors were 3.7 % , 16.3 % , 41.0 % , and 66.7 % , respectively ( P<.05 ) . The presence of three or more risk factors was associated with a positive predictive value of 66.7 % and a negative predictive value of 86.4 % . CONCLUSION Although additional studies are needed , these findings suggest that a simple four-item risk score can identify older patients with HF at high risk of dying within 6 months . This may enable clinicians to better advise patients about prognosis , adjust management accordingly , and if appropriate , facilitate referral for hospice care . Conversely , patients with a more-favorable prognosis may be suitable c and i date s for more-aggressive interventions BACKGROUND The model for end-stage liver disease ( MELD ) , which employs objective variables , statistical weighting and a continuous scale , has replaced the Child-Turcotte-Pugh ( CTP ) classification as the scoring system of choice in several liver transplant centers . However , the predictive ability of MELD has never been prospect ively evaluated in India . The aim of this study was to examine the MELD score , the CTP score and the recently proposed modified CTP score in Indian patients with liver cirrhosis to determine their correlation and compare their prognostic significance for short-term survival . METHODS A total of 76 patients with cirrhosis ( mean age 46.97 years ) were prospect ively evaluated and followed up for 6 months . MELD score , CTP score and modified CTP score were calculated at baseline . The correlation between variables was evaluated by Pearson 's correlation test . Receiver-operating characteristic ( ROC ) curves were used to determine the cutoff values for each score with the best sensitivity and specificity in discriminating between patients who survived and those who died . RESULTS Alcoholic liver disease was the most common ( 50 % ) etiology of cirrhosis . MELD score and CTP score showed very good correlation ( Pearson correlation r = 0.983 ) . ROC curve showed area under curve ( c-statistics ) for MELD score , CTP score and modified CTP score as 0.764 , 0.804 and 0.817 , respectively . CONCLUSION The MELD score was not found to be superior to CTP score and modified CTP score for short-term prognostication of patients with cirrhosis in this study INTRODUCTION The increasing prevalence of end-stage renal disease ( ESRD ) is an important public health issue due to the high costs of kidney replacement therapies . We examined the impact of ethnicity and other factors in ESRD management and hospitalisation in a multiracial Asian population in the fi rst year after diagnosis . MATERIAL S AND METHODS We analysed a prospect ively collected data base of 168 new ESRD patients from the National University Hospital , Singapore ( NUH ) in 2005 . Univariate and multivariate analyses were performed to assess factors for mortality and hospitalisation . RESULTS Sixteen patients eventually chose conservative treatment , 102 haemodialysis , 41 peritoneal dialysis and 9 patients underwent kidney transplantation for their long-term treatment . Although more Chinese patients had dialysis plans ( 56.7 % vs 36.8 % , P = 0.022 ) , many still required urgent dialysis initiation via catheters ( 61.3 % ) . These dialysed patients who required urgent treatment had more admissions ( 3.6 vs 2.6 , P = 0.023 ) and longer length of stay ( 9.3 days , P = 0.014 ) . Approximately 40 ( 7.4 % ) admissions were related to vascular access complications ( thromboses , dislodgements and infections ) , and 15 ( 2.8 % ) were for new tunnelled catheter insertions . Deaths were 23.8 % in the fi rst year after diagnosis and median survival was 125 days . Age , fi nal treatment modality , type of therapy centre , history of coronary artery disease , left ventricular ejection fraction ( LVEF ) < 50 % , and having no plans for dialysis were associated with mortality . CONCLUSIONS The care of ESRD patients requires substantial commitment of healthcare re sources particularly in the fi rst year after diagnosis . Steps to reduce urgent initiation of dialysis will help reduce re source utilisation and improve patient outcomes The objective of this study was to evaluate differences in mortality over the first year of renal replacement therapy ( RRT ) between elderly patients starting treatment on hemodialysis ( HD ) versus peritoneal dialysis ( PD ) . For the period of 1991 to mid-1996 , this study defined an inception cohort of all patients aged > 65 yr with new-onset chronic RRT who were New Jersey Medicare and /or Medicaid beneficiaries in the year before RRT and who had been diagnosed with renal disease more than 1 yr before RRT . Propensity scores were calculated for first treatment assignment from a large number of baseline covariates . Mortality was then compared among patients initially assigned to HD versus PD using multivariate 90-d interval Cox models controlled for propensity scores and center stratification . Peritoneal dialysis starters had a 16 % higher rate of death during the first 90 d of RRT compared with HD patients ( hazard ratio [ HR ] , 1.16 ; 95 % confidence interval [ CI ] , 0.96 to 1.42 ) ] . Mortality did not differ between day 91 and 180 ( HR , 1.03 ; 95 % CI , 0.71 to 1.51 ) . Thereafter , PD starters again died at a higher rate ( HR , 1.45 ; 95 % CI , 1.07 to 1.98 ) . These findings were more pronounced among patients with diabetes . Sensitivity analyses using more stringent criteria to ensure that first treatment choice reflected long-term treatment choice confirmed the presence of an association between PD and mortality . In conclusion , compared with HD , peritoneal dialysis appears to be associated with higher mortality among older patients , particularly among those with diabetes , even after controlling for a large number of risk factors for mortality , propensity scores to control for nonr and om treatment assignment , and center stratification BACKGROUND & AIMS Although renal failure is a common complication of sepsis and patients with cirrhosis frequently develop sepsis , there have been no studies specifically assessing renal function in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis . The aim of this study was to investigate prospect ively the frequency , characteristics , and outcome of renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis . METHODS One hundred six consecutive patients with cirrhosis and sepsis were studied prospect ively . Patients with spontaneous bacterial peritonitis were excluded . RESULTS Twenty-nine out of 106 patients ( 27 % ) with cirrhosis and sepsis developed acute renal failure as compared with only 8 of 100 patients ( 8 % ) from a control group of cirrhotic patients without infection ( P < .0001 ) . Renal failure in the sepsis group was reversible in 22 ( 76 % ; 21 % of all patients ) patients and nonreversible in 7 ( 24 % ; 6 % of all patients ) patients . Renal failure was associated with impairment of effective arterial blood volume , without evidence of tubular damage . The occurrence and type of renal failure correlated strongly with mortality ( mortality at 3 months : nonreversible renal failure , 100 % ; reversible renal failure , 55 % ; no renal failure , 13 % ) . Among variables obtained at diagnosis of sepsis , the Model for End-Stage Liver Disease ( MELD ) score was the only independent predictive factor of mortality . CONCLUSIONS Renal failure is common in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis and is associated with arterial underfilling and renal vasoconstriction . Outcome is poor , even in the setting of reversible renal failure . The MELD score is the best prognostic marker of patients with cirrhosis and sepsis BACKGROUND / AIMS Endoscopic sclerotherapy is considered a first line therapy to stop bleeding from esophageal varices , but acute variceal bleeding is still associated with high risk of rebleeding and death . We compared the use of octreotide with endoscopic sclerotherapy versus sclerotherapy alone to control acute variceal bleeding and prevent rebleeding in patients with cirrhosis . METHODOLOGY In a prospect i ve controlled trial , 68 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were r and omly assigned to receive a continuous infusion of octreotide or placebo for two days . The primary outcome measure was 7-day mortality . RESULTS After seven days the overall mortality was 19.1 % , and the proportion of patients who died in octreotide group ( 8 of 40 , or 20 % ) was similar to the placebo group ( 5 of 28 , or 17.85 % ; p = 0.74 ) . Rebleeding occurred in 20.6 % ( 14 of 68 patients ) , being 20 % ( 8 of 40 ) in the octreotide group vs. 21.4 % ( 6 of 28 ) in the placebo group ( p = 0.88 ) . The mean number of units of blood transfused after sclerotherapy was 2.05 units in the octreotide group vs. 2.08 units in the placebo group ( p = 0.96 ) . Thirty patients needed intensive care support ( 20 of 40 in the octreotide group vs. 10 of 28 in the placebo group ; p = 0.24 ) . The differences remained without statistical significance even after adjustment for hepatic function and endoscopic bleeding stigmata by a linear regression model analysis test . CONCLUSIONS In patients with cirrhosis , octreotide intravenous per 48h associated with sclerotherapy is not superior to sclerotherapy alone in terms of 7-day mortality , frequency of rebleeding , number of units of packet red blood cell transfusion and length of stay in intensive care setting Background . In the absence of r and omized trials comparing heart transplantation ( HTx ) with medical therapy for the treatment of advanced heart failure ( HF ) , the role of HTx remains uncertain . Using data from a national audit , we examined the effect of HTx on HF mortality in the Unite Kingdom . Methods . Two thous and two hundred nineteen adults listed for HTx from April 1995 to October 2003 and followed to June 2007 were analyzed . In a sub study of 627 patients from two centers , ambulatory patients were risk-stratified by the heart failure survival score . A time-dependent nonproportional hazards model was used to estimate the effect of HTx . Results . Fourteen percent of patients were nonambulatory at listing . Death while waiting was higher among nonambulatory patients ( 19 % vs. 14 % in the ambulatory group , P<0.001 with 76 % vs. 71 % being transplanted ) . Posttransplant survival to 3 years was 78 % and 75 % in nonambulatory and ambulatory groups , respectively ( P=0.68 ) . HTx was found to benefit all groups . For nonambulatory patients , the risk of dying after HTx fell below the risk of dying while waiting after 10 days ( 95 % CI 2–18 ) with a net survival benefit after 26 days ( 95 % CI 5–53 ) ; for the ambulatory group the estimates were 42 days ( 95 % CI 36–47 ) and 274 days ( 95 % CI 214–359 ) , respectively . In the sub study cohort net survival benefit was seen after 20 , 124 , 291 , and 729 days for the nonambulatory , high , moderate , and low heart failure survival score risk groups , respectively . Conclusion . HTx remains an effective treatment of advanced HF . Prioritization of patients with refractory HF is rational , because they are the first to benefit |
2,350 | 30,670,501 | Consistent evidence was found that SOs ’ positive and encouraging attitudes regarding work participation , encouragement and motivating behaviour and open communication with patients are facilitators for work participation .
Consistently reported barriers were SOs ’ positive attitudes towards sickness absence and advise , encouragement or pressure to refrain from work .
Conclusions Our findings show that several cognitions and behaviours of SOs can facilitate or hinder work participation of individuals with a chronic disease .
Intervening on these factors by involving SOs in disability prevention and return to work intervention strategies may be beneficial . | Objective It is widely recognised that significant others ( SOs ) , such as a partner , family member or friend , can influence health outcomes of individuals with a chronic disease .
However , not much is known about which specific cognitions ( ie , illness perceptions and expectation of work ability ) and behaviours ( eg , emotional and practical support ) of SOs influence work participation .
Therefore , we aim ed to identify cognitions and behaviours of SOs that are related to work participation of individuals with a chronic disease . | A prospect i ve study of patients with chronic low-back pain was made to determine the significance of the patient 's own prediction of the outcome of a vocational rehabilitation program . Fifty-two patients were screened , and their work situation determined one and 4 years after the rehabilitation program was started . The patients predicted the outcome correctly in 69 % , with a sensitivity of 68 % and a specificity of 71 % . A statistically significant correlation was found between the patient 's prediction and the recommendations given by the rehabilitation unit OBJECTIVE There is accumulating evidence to indicate that the illness representations of significant others are important for underst and ing patients ' responses to chronic disease . The aims of the present study were to ( a ) assess the illness representations of patients with type 2 diabetes and their partners , ( b ) determine the extent of agreement between patient and partner representations , and ( c ) examine whether partners ' representations mediate the relationships between patients ' representations and their prospect i ve self-management behaviors . METHODS Patients ' and partners ' representations of diabetes were assessed with the Revised Illness Perception Question naire [ Moss-Morris R , Weinman J , Petrie K , Horne R , Cameron LD , Buick , D. The revised illness perception question naire ( IPQ-R ) . Psychol Health 2002;17:116 ] at baseline ( n=164 ) . Self-management behaviors were assessed 12 months later with self-report measures of physical activity , medication , and a food frequency question naire . RESULTS Patients scored lower on the illness coherence dimension , indicating that they reported a poorer underst and ing of the condition ( t=-2.66 , df=163 , P=.009 ) relative to their partners . Patients demonstrated higher scores for personal control than their partners ( t=2.01 , df=163 , P=.046 ) . Mediational analyses indicated that partners ' perceived timeline of diabetes partially mediated the relationship between patients ' representations and their self-management behaviors including physical activity and dietary intake . In addition , partners ' personal control representations partially mediated the relationship between patients ' representations and physical activity . CONCLUSION It was demonstrated that patient-partner dyads generally share similar representations of type 2 diabetes and perceived control over the condition . Furthermore , there was evidence that partners ' representations partially mediated the relationships between patients ' representations and their prospect i ve self-management behaviors Dysfunctional beliefs and attitudes about sleep are presumed to play an important mediating role in perpetuating insomnia . The present study evaluated the impact of cognitive-behavioral and pharmacological treatments for insomnia on sleep-related beliefs and attitudes and the relationship between those changes and sleep improvements . The participants were older adults with chronic and primary insomnia . They received cognitive-behavior therapy ( CBT ) , pharmacotherapy ( PCT ) , combined CBT+PCT ( COMB ) , or a medication placebo ( PLA ) . In addition to daily sleep diaries and sleep laboratory measures , the participants completed the dysfunctional beliefs and attitudes about sleep scale ( DBAS ) at baseline and posttreatment , and at 3- , 12- and 24-month follow-up assessment s. The results showed that CBT and COMB treatments produced greater improvements of beliefs and attitudes about sleep at posttreatment than PCT and PLA . Reductions of DBAS scores were significantly correlated with improvements of sleep efficiency as measured by daily sleep diaries and by polysomnography . In addition , more adaptive beliefs and attitudes about sleep at posttreatment were associated with better maintenance of sleep improvements at follow-ups . These findings highlight the importance of targeting sleep-related beliefs and attitudes in the treatment of insomnia Medication noncompliance occurs among as many as one-third to one-half of all medical and psychiatric out patients . Noncompliance has serious consequences for individuals diagnosed with schizophrenia , often result ing in higher rates of relapse and rehospitalization , and poorer community adjustment . Health education interventions have been shown to be effective in promoting compliance among patients with chronic medical illnesses such as hypertension or diabetes , but there have been few r and omized trials of this approach among patients with chronic psychiatric disorders . This paper presents the results of an application of health education among a group of male psychiatric out patients . Two interventions were developed which used health education techniques to 1 ) engage families or significant others as active participants in the aftercare process , and 2 ) train patients to become effective health care consumers . A total of 418 individuals participated in a six-month trial over a four-year study . Both interventions significantly improved medication compliance among those who received them . The results show that comparatively brief interventions can significantly alter medication compliance behavior and improve the quality of life for patients with chronic psychiatric disorders Although alcohol use disorders ( AUDs ) adversely affect women , research on efficacious treatments for women is limited . In this r and omized efficacy trial of 102 heterosexual women with AUDs , the authors compared alcohol behavioral couple therapy ( ABCT ) and alcohol behavioral individual therapy ( ABIT ) on percentage of days abstinent ( PDA ) and percentage of days of heavy drinking ( PDH ) over 6 months of treatment and 12 months of posttreatment follow-up . Baseline relationship functioning and comorbid disorders were tested as moderators of outcome . Piecewise linear growth models were used to model outcomes . During treatment , women increased their PDA and decreased their PDH , with significantly greater improvements in ABCT than in ABIT ( d = 0.59 for PDA ; d = 0.79 for PDH ) . Differences favoring ABCT were maintained during follow-up . Women with poorer baseline relationship functioning improved more on PDA during treatment with ABCT than with ABIT . For PDH , results during treatment and follow-up favored ABCT for women with better baseline relationship functioning . ABCT result ed in better outcomes than ABIT for women with Axis I disorders at the end of follow-up ( PDA ) , and for women with Axis II disorders at the end of treatment ( PDA ) and at the end of follow-up ( PDH ) |
2,351 | 31,383,021 | Conclusions No significant differences in all-cause mortality or the duration of hospital stay were found in neonates with suspected or proven sepsis treated with the four types of immunotherapies and those treated with placebo | Background To investigate the efficacies of different immunotherapies in neonates with suspected or proven sepsis . | Background : Bacterial sepsis is one of the major causes of mortality in newborn infants . Mortality increases when sepsis is associated with neutropenia . Material s and Methods : We conducted a prospect i ve , r and omized , double-blind , placebo-controlled trial of recombinant human granulocyte colony-stimulating factor on preterm neonates ( gestational age ( GA ) < 34 weeks ) with sepsis and absolute neutrophil count ( ANC ) of < 1500 cells/mm3 . Mortality , duration of Neonatal Intensive Care Unit ( NICU ) stay , hematological parameters ( ANC , platelet count , and total leukocyte count ) were compared between the two groups . The GCSF group ( n=39 ) received GCSF intravenously in a single daily dose of 10 μg/kg/day in a 5 % dextrose solution over 20 - 40 min for three consecutive days , while the control group ( n=39 ) received placebo of an equivalent volume of 5 % dextrose . Results : Baseline demographic profile among the two groups was comparable . Mortality rate in the GCSF group was significantly lower than in the control group ( 10 % vs. 35 % ; P<0.05 ) . By day 3 of treatment , ANC in the GCSF group was significantly higher ( 3521±327 ) compared to 2094±460 in the control group , with P value being < 0.05 . Duration of NICU stay also decreased significantly in the GCSF group . Conclusion : The administration of GCSF in preterms with septicemia and neutropenia result ed in lower mortality rates . Further studies are required to confirm our results and establish this adjunctive therapy in neonatal sepsis Neonates are susceptible to septicemia secondary to quantitative and qualitative neutrophilic defects . Granulocyte colony-stimulating factor ( G-CSF ) stimulates myeloid progenitor cell proliferation and induces selective neutrophil functions . The authors aim ed to evaluate the effect of G-CSF administration in septic neonates on neutrophil production and CD11b expression . Sixty septic neonates were r and omized to receive intravenous G-CSF 10 μg/kg/day for 3 days ( G-CSF group , n = 30 ) , or not to receive G-CSF ( non – G-CSF group , n = 30 ) . Thirty healthy newborns were included as controls . Laboratory investigations included complete blood count , C-reactive protein , blood culture , renal and liver function tests , and assessment of neutrophilic expression of CD11b . Total leukocytes count ( TLC ) , absolute neutrophil count ( ANC ) , and immature myeloid cell count in G-CSF group showed significant difference between post– and pre – G-CSF levels . TLC , ANC , immature myeloid cell count and immature/total myeloid cells ratio were higher in G-CSF group compared to non – G-CSF group on days 1 and 3 . Higher neutrophilic expression of CD11b was reported in both septic groups on day 0 compared to control group . On day 5 , CD11b was higher in G-CSF group than non – G-CSF group . G-CSF improved CD11b% in neutropenic and non-neutropenic septic neonates . No significant difference was found between pre- and posttreatment renal and liver function tests . Lower duration of antibiotic intake and hospitalization was observed in G-CSF group compared to non – G-CSF group . G-CSF administration as an adjuvant therapy for neonatal septicemia , whether neutropenic or not , improves neutrophilic count and function and contributed to early healing from sepsis BACKGROUND To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor , recombinant human granulocyte-macrophage colony-stimulating factor ( rhG-CSF ) to treat sepsis in neutropenic preterm infants . METHODS Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children 's Educational and Training Hospital , Kozyatağı/Istanbul , Turkey between January 2008 and January 2010 were enrolled . Patients were r and omized either to receive rhG-CSF plus empirical antibiotics ( Group I ) or empirical antibiotics alone ( Group II ) . Clinical features were recorded . Daily complete blood count was performed until neutropenia subsided . Data were analyzed using SPSS version 11.5 . RESULTS Thirty-three infants received rhG-CSF plus antibiotic treatment and 23 infants received antibiotic treatment . No drug-related adverse event was recorded . Absolute neutrophil count values were significantly higher on the 2(nd ) study day and 3(rd ) study day in Group I. Short-term mortality did not differ between the groups . CONCLUSION Treatment with rhG-CSF result ed in a more rapid recovery of ANC in neutropenic preterm infants . However , no reduction in short-term mortality was documented In a prospect i ve double‐blind study , st and ard intravenous immunoglobulin ( IVIG ) was compared with an IgM‐enriched IVIG in the treatment of neonatal sepsis . The two treatment groups were also compared with matched controls . One hundred and thirty babies ( 65 in each group ) ranging from 0 to 24 days old , 480 to 4200 g in weight and born between 24 and 42 weeks of gestation who had , or were suspected of having , sepsis were given either st and ard IVIG or IgM‐enriched IVIG ( 250 mg/kg per day ) for 4 days in addition to supportive and antibiotic therapy . A further 65 babies who received similar supportive , antibiotic and fluids but not IVIG were used as matched controls . Mortality from infection in ‘ culture proven sepsis ’ was 3/44 ( 6·8 % ) in the IgM‐enriched IVIG group , 6/42 ( 14·2 % ) in the st and ard IVIG group , and 11/43 ( 25·5 % ) in the control group ( P = 0·017 , IgM versus control , P = 019 st and ard IVIG versus control ) . There was no statistical difference in the outcome between the two immunoglobulin therapy groups ( P = 0·25 ) . The study indicates that IVIG improves outcome in neonatal sepsis when used as an adjunct to supportive and antibiotic therapy , but larger studies are required to confirm this OBJECTIVES The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor ( rhG-CSF ) for the treatment of very low birthweight infants ( VLBW ) with sepsis and relative neutropenia , specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality . Secondary objectives were to evaluate duration of ventilation , intensive care , and antibiotic use as markers of efficacy . DESIGN Neonates ( ⩽ 28 days ) in intensive care , with birth weights of 500–1500 g , absolute neutrophil count ( ANC ) of ⩽ 5 × 109/l , and clinical evidence of sepsis , were r and omly assigned to receive either rhG-CSF ( 10 μg/kg/day ) administered intravenously ( n = 13 ) , or placebo ( n = 15 ) for a maximum of 14 days , in addition to st and ard treatment and antibiotics . All adverse events , oxygenation index , incidence of thrombocytopenia , all cause mortality , duration of ventilation , intensive care and antibiotic treatment , and ANC recovery were compared between the two groups . RESULTS Adverse events and oxygenation index were not increased by , and thrombocytopenia was not attributable to , treatment with rhG-CSF . At 6 and 12 months postmenstrual age , there were significantly fewer deaths in the group receiving rhG-CSF ( 1/13 v 7/15 ; p ⩽ 0.038 ) . There was a non-significant trend towards a reduction in duration of ventilation , intensive care , and antibiotic use in the rhG-CSF group . There was a significantly more rapid increase in ANC in the rhG-CSF treated babies ( p < 0.001 ) . CONCLUSIONS In a small r and omised placebo controlled trial in a highly selected group of neonates , adjuvant treatment with rhG-CSF increased ANC rapidly , and no treatment related adverse events were identified . Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group . A large trial investigating efficacy in a similar group of neonates is warranted . Key messages rhG-CSF increases the absolute neutrophil count in very low birthweight infants with neutropenia and sepsis Thrombocytopenia is not an effect of rhG-CSF treatment Potential beneficial effects on long term survival require further In a double blind controlled study antilipopolysaccharide gammaglobulin given intramuscularly did not reduce mortality in low birthweight babies suffering from septicaemia . It did , however , reduce the recovery period of survivors from 310 to 120 hours Thirty-seven neonates with confirmed septicemia through hemoculture were studied . Of them , 18 were treated with antibiotic and the other 19 were given 500 mg/kg of intravenous immunoglobin with a pH of 4.25 ( IGIV ) . The greater part of the neonates in this study were full-term or near full-term . There were no differences in age , gestational age and weight , nor in mortality , the bacterias found and the clinical manifestations which were seen in both groups . Yet , the hospitalary stay was shorter for those in the group treated with IGIV ( 13.9 + /- 5.7 days ) than in the trial group ( 24.4 + /- 10.3 days ) ; as well as some clinical manifestations like diarrhea and splenomegalia ( P < 0.05 ) . The serum of the neonates from the IGIV group showed a greater capacity of opsonization and inhibition of bacterial growth than those in the trial group ( P < 0.001 ) , coinciding with an increase of 300 mg/dL in the serum levels of IgG of the group treated with IGIV from the 3rd day of the study and the C4 and B-Properdine factor serum levels from the 7th day of the study , while in the trial group , there were no changes in these factors ( P < 0.001 ) . Even though no differences were seen in the mortality rate due to septicemia , the results suggest a much shorter evolution of the illness in patients treated with IGIV . In addition , the serum of those patients treated with IGIV showed in in vitro studies , a better bacteriostatic activity and a better capacity to opsonize the bacterias isolated in the hemocultures . ( ABSTRACT TRUNCATED AT 250 WORDS Objective . Preterm neonates undergoing intensive care have high morbidity from sepsis . These infants also frequently develop neutropenia , and when this is associated with sepsis , mortality is high . This study investigates the potential for granulocyte-macrophage colony-stimulating factor ( GM-CSF ) to effect a clinical ly relevant increase in neutrophil number when used prophylactically in high-risk preterm neonates , and assesses its safety in this population . Design . In an open , r and omized , controlled study , 75 neonates ( 25 small for gestational age ) < 32 weeks gestation were r and omized to receive GM-CSF ( 10 μg/kg/d ) by subcutaneous injection for 5 days from < 72 hours after birth , or to a control group . The primary outcome measure was the neutrophil count during 14 days from study entry . The infants were monitored for potential toxicity . Clinical outcomes , sepsis , and mortality , were recorded , but this initial study was not design ed to address clinical benefit . Results . Prophylactic GM-CSF therapy completely abolished neutropenia in treated infants , when both well and septic , throughout the period of study . Neutropenia ( ≤1.7 × 109/L ) developed in 16 of 39 control infants . Five control infants experienced an acute decrease in neutrophil count coincident with the onset of sepsis . There was no evidence of hematologic , respiratory , or gastrointestinal toxicity in treated infants . Treated infants had a trend to fewer symptomatic , blood culture positive septic episodes than controls during 2 weeks from study entry ( 11/36 vs 18/39 ) . Conclusion . Five-day prophylactic GM-CSF completely abolishes postnatal neutropenia and sepsis-induced neutropenia in preterm neonates at high risk of sepsis , and so removes an important risk factor for sepsis and sepsis-related mortality . GM-CSF , preterm neonates , neutropenia , sepsis Abstract The objective of this study was to investigate the effect of treatment with recombinant human granulocyte-colony stimulating factor ( rhG-CSF ) on the neutrophil count and function of preterm neonates with documented sepsis . For this purpose 62 preterm neonates with proven sepsis and 19 healthy preterm ones were studied . Of the 62 patients , 27 septic neonates had an absolute neutrophil count ( ANC ) > 5000/mm3 ( group A ) and were scheduled not to receive rhG-CSF and 35/62 had an ANC < 5000/mm3 ( n= 35 ) and were r and omly assigned either to receive rhG-CSF ( group B ) or not to receive it ( group C ) . rhG-CSF ( 10 μg/kg ) was administered for 3 consecutive days ( 0 , 1 , 2 ) . The ANC , plasma levels of G-CSF ( ELISA ) , neutrophil respiratory burst activity ( NRBA ) and neutrophil expression of CD11a , CD11b and CD11c ( flow cytometry ) were measured in all septic neonates on days 0 ( onset of sepsis ) , 1 , 3 and 5 and in the healthy neonates once within the first 2 days of life . We found that on day 0 , G-CSF levels of all groups of septic neonates were significantly higher than those of the healthy ones . The highest levels were observed in group A. NRBA was diminished only in groups B and C and the expression of CD11a and CD11c was reduced in all groups of septic neonates . Administration of rhG-CSF result ed in a rapid and significant increase in ANC , NRBA and CD11a , CD11b and CD11c expression that persisted throughout the follow up . Conclusion The administration of granulocyte colony stimulating factor to septic neonates significantly increases the absolute granulocyte count and enhances the neutrophil respiratory burst and β2 integrin expression Despite the development of newer generation of antibiotics , mortality from neonatal sepsis remains high . In a prospect i ve , r and omized study , we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis . Two groups of 30 infants each ( matched for gestational age , sex , weight , and other variables ) were r and omly allocated to receive either antibiotics alone ( control group ) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously ( immunotherapy group ) . Mortality from sepsis in the control group was 20 % ( 6/30 ) , while in the immunotherapy group it was 3.3 % ( 1/30 ) . We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis Blood cultures were performed on 141 newborn infants who had clinical features or laboratory data indicative of sepsis between January 1993 and April 1995 . Clinical features included respiratory deterioration , poor activity , abdominal distension and apnea . Abnormal laboratory data included leukocytosis , leukopenia , elevated C-reactive protein values or increased immature neutrophil counts . The 141 neonates with suspected bacterial infections received antibiotic therapy and were r and omly divided into two groups . One group received a single dose of 500 mg/kg of intravenous immunoglobulin ( IVIG ) , while the other group received placebo ( 0.9 % sodium chloride ) . Patients with negative blood cultures were excluded from this study . A total of 56 neonates with positive blood cultures were enrolled in this study . The IVIG-treated group and placebo-treated group consisted of 10 premature and 18 term neonates , respectively . Another 10 healthy premature and healthy 18 term neonates were selected as the control group . Serum IgG values increased significantly 1 and 2 weeks after administration of IVIG in the IVIG-treated group . However , there was no significant difference in the duration of treatment and mortality between the IVIG-treated and placebo-treated groups . Our preliminary observations suggest that administration of 500 mg/kg IVIG to neonates with sepsis had no effect on reducing mortality . In addition , it shortened neither the duration of antibiotic therapy nor hospitalization . No adverse reactions to the IVIG infusions were noted during the study OBJECTIVES To determine whether adjunctive therapy with recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival and to assess its safety compared with conventional therapy in a control group . STUDY DESIGN This prospect i ve , r and omized , controlled trial was performed in 60 infants with neutropenia and clinical signs of sepsis . A subcutaneous injection of rhGM-CSF ( 5 microgram/kg/day ) was administered to 30 of the patients for 7 consecutive days . Hematologic parameters ( absolute neutrophil , eosinophil , monocyte , lymphocyte counts , and platelet number ) and outcome were compared with 30 conventionally treated ( control ) patients . RESULTS Twenty-five patients from the GM-CSF-treated group and 24 from the conventionally treated group had early-onset sepsis ( < /=3 days ' postnatal age ) , and the other 11 patients had late-onset sepsis ( > 3 days ' postnatal age ) . There was no difference between groups in terms of birth weight ; gestational age ; gender ; maturity ; maternal age ; and incidence of prolonged rupture of membranes , maternal hypertension , or severity of sepsis . All neonates tolerated GM-CSF well with no adverse reactions . The absolute neutrophil count on day 7 was significantly increased in the GM-CSF-treated group compared with the conventionally treated group : 8088 + /- 2822/mm(3 ) versus 2757 + /- 823/mm(3 ) . The mean platelet count was significantly higher on days 14 in the GM-CSF-treated group compared with conventionally treated group : 266 867 + /- 55 102/mm(3 ) versus 229 200 + /- 52 317/mm(3 ) . Hematologic parameters were otherwise similar between groups before treatment and on day 28 . Twenty-seven neonates in the rh-GMCSF group and 21 in the control group survived to hospital discharge . The mortality rate in the rhGM-CSF group ( 10 % ) was significantly lower than in the conventionally treated group ( 30 % ) . CONCLUSION Treatment with rhGM-CSF is associated with an increase in absolute neutrophil , eosinophil , monocyte , lymphocyte , and platelet counts and decreased mortality in critically ill septic neutropenic neonates . These results suggest that rhGM-CSF may be effective in the treatment of neonatal sepsis with neutropenia , and further r and omized trials are needed to confirm its beneficial effects Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection . To determine whether intravenous immune globulin ( IVIG ) therapy improves survival rates in early-onset sepsis , we prospect ively entered 753 neonates ( birth weight 500 to 2000 gm , gestation less than or equal to 34 weeks , age less than or equal to 12 hours ) into a multicenter , double-blind , controlled trial . Blood culture specimens were obtained and infants r and omly assigned to receive 10 ml ( per kilogram ) intravenously of a selected IVIG ( 500 mg/kg ) or albumin ( 5 mg/kg ) preparation . Maternal and neonatal risk factors were not different between groups . Thirty-one babies ( 4.2 % ) had early-onset sepsis ; the causative organisms were group B streptococcus ( 12 babies ) , Escherichia coli ( 6 ) , and others ( 13 ) . Of these 31 neonates , 7 ( 23 % ) died . Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment ( p less than 0.05 ) . During these 7 days , 5 ( 30 % ) of 17 albumin-treated and none of 14 IVIG-treated patients died ( p less than 0.05 ) . The survival rate at 56 days of age , however , was not significantly improved . Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody . Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy ( 0.5 % ) than in those receiving albumin . The IVIG therapy in neonates with early-onset sepsis , while reducing the early mortality rate , did not significantly affect the overall survival rate . Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens The therapeutic effect of a polyvalent immunoglobulin preparation for intravenous use was tested in 82 newborns with bacterial infections . 35 of the children had neonatal sepsis , whereas in the other 47 bacteremia was not detectable . Treatment consisted either of antibiotics only or of antibiotics combined wih immunoglobulin SRK on an alternating basis for the first six days . Immunoglobulin substitution was tolerated without complications . In the group of infants with neonatal sepsis , two of 20 ( 10 % ) who were substituted with immunoglobulin and four of 15 ( 26 % ) who received no immunoglobulin died . Likewise , in the group of patients without detectable bacteremia , two of 21 on immunoglobulin substitution ( 10 % ) and four of the 26 who were not substituted ( 15 % ) died . The low mortality observed in the present study was attributed to efforts at early diagnosis and conventional early treatment on the one h and , and to immunoglobulin substitution on the other . To detect possible late sequelae of immunoglobulin therapy , particularly in hypogammaglobulinemic premature newborns , clinical and immunological investigations were performed in the septic patient group at the age of one to four years . There were no indications that administration of immunoglobulins during the neonatal period might have had an adverse effect on psychomotor and somatic development or on the immunological maturation of the infants Background . To reduce morbidity and mortality adjuvant cytokine therapy was administered to septic neonates with variable results . The objective of this case series was to compare the effectiveness of recombinant human granulocyte-macrophage colony-stimulating factor ( rhuGM-CSF ) and recombinant granulocyte colony-stimulating factor ( rG-CSF ) with that of placebo in correcting neutropenia induced by sepsis . Methods . Symptomatic , septic premature neonates with or without a positive blood culture were eligible . Twenty-eight patients were r and omized : 10 received rG-CSF ( 5 & mgr;g/kg/dose iv twice a day ) ; 10 received rhuGM-CSF ( 4 & mgr;g/kg/dose iv twice a day ) and 8 received placebo for a maximum of 7 days , or until an absolute neutrophil count ( ANC ) of 10 000 cells/mm3 was reached . Results . A significant increase in the ANC above the baseline was present on Day 2 in the rG-CSF group ( P = 0.015 ) and on Day 5 in the rhuGM-CSF ( P = 0.002 ) and placebo ( P = 0.027 ) groups . The ANC of the rG-CSF group was significantly above that in the rhuGM-CSF and placebo groups on Day 7 ( P = 0.03 ) . Mortality and neonatal intensive care unit morbidity was not significantly different between the groups . Conclusion . The neutrophil count in the rG-CSF-treated group increased significantly faster than that in the placebo or rhuGM-CSF group OBJECTIVE : To evaluate the efficacy of the recombinant human granulocyte colony-stimulating factor ( rhG-CSF ) in the treatment of early-onset neonatal sepsis among premature infants . MATERIAL S AND METHODS : A double-blind , r and omized , placebo-controlled trial was performed among forty-four preterm neonates who had " clinical diagnosis " of early-onset sepsis . The treatment group ( n=22 ) received 10 micro g/kg/d of rhG-CSF , IV once daily for three consecutive days , and the placebo group ( n=22 ) received the same volume of a visually-indistinguishable vehicle . Prior to the first dose , and prior to the second and third doses , and again 10 days after the first dose , we measured tumor necrosis factor-a , interleukin-6 , granulocyte-macrophagocyte colony-stimulating factor , G-CSF , leukocyte count , absolute neutrophil count , immature/total neutrophil ratio , platelet count , and hemoglobin concentration . A bone marrow aspiration was performed seven days after the first dose , and both the neutrophil storage pool ( NSP ) percent and the NSP/NPP ( neutrophil proliferative pool ) ratios were tabulated . RESULTS : The treatment and placebo groups were of similar gestational age ( 29-/+ 3 vs 31-/+ 3 weeks ) and birth weight ( 1376 -/+ 491 vs 1404 -/+ 508 grams ) . They had similar Apgar scores and 24 hour SNAP scores . No deaths occurred during the first week of life among the treatment group while three deaths occurred in the placebo group . RhG-CSF treatment did not alter the serum concentrations of the cytokines measured ( except for G-CSF ) . Serum G-CSF levels , blood leukocyte counts , absolute neutrophil counts , NSP percentages , and NSP/NPP ratios were higher in the treatment group 24 hours and 72 hours after dosing . The occurrence of a subsequent infection over the two week period following dosing was significantly lower in the treatment group ( n=2 ) than in the placebo group ( n=9 ; p<0.02 , RR 0.19 [ 0.05 - 0.78 ] ) . The overall mortality rate during the entire hospitalization was not different between treatment and placebo groups . CONCLUSIONS : Administration of rhG-CSF to premature neonates with the clinical diagnosis of early-onset sepsis was associated with lower incidence of nosocomial infection over the ensuing three weeks period , but it did not change the overall mortality rate A r and omized , double-blinded , placebo-controlled trial was conducted of early administration of recombinant granulocyte colony-stimulating factor ( rGCSF ) to 40 non-neutropenic , preterm infants between 33 and 36 weeks of gestational age with the diagnosis of presumed sepsis . The treatment group ( n = 20 ) received 5 μg/kg per day of intravenous rGCSF once daily for 3 d and the control group ( n = 20 ) received the same volume of physiological serum . Immediately before the first dose and on the 4th day , plasma levels of GCSF and tumour necrosis factor-α ( TNF-α ) , absolute neutrophil counts ( ANC ) , immature neutrophil count ( INC ) , immature/total neutrophil ( I/T ) ratios and platelet counts were determined . At study entry , the plasma GCSF and TNF-α levels were similar . On day 4 , there was no significant change in GCSF levels in either groups , whereas there was a significant decrease in TNF-α levels in the treatment group . ANC and INC of the treatment group also increased significantly . The I/T ratio continued at the same level in the treatment group , but decreased significantly on days 4 and 7 day in the control group . The length of time on the neonatal intensive care unit ( NICU ) was significantly shorter in the treatment group . In conclusion , early administration of 3 daily doses of rGCSF ( 5 μg/kg per day ) to non-neutropenic , preterm infants who had presumed sepsis increased circulating ANC and INC , decreased plasma TNF-α levels and shortened the length of time on the NICU OBJECTIVE To investigate the effectivity of pentoxifylline ( PTX ) and immunoglobulin M (IgM)-enriched intravenous immunoglobulin ( IVIG ) therapy in the treatment of neonatal sepsis ( NS ) , alone or in combination . STUDY DESIGN This was a prospect i ve , double-blind , controlled study . Newborns with suspicion of sepsis were enrolled in the study . The patients were separated into four groups according to treatment protocol : Group 1 = placebo , Group 2 = pentoxifylline , Group 3 = IgM-enriched IVIG , and Group 4 = pentoxifylline + IgM-enriched IVIG . Blood sample s were taken for C-reactive protein , interleukin-6 , neutrophil CD64 expression , and tumor necrosis factor-alfa measurements immediately before treatment ( 1st day ) , and measurements were repeated on the 2nd and 4th days of the therapy . RESULTS A total of 204 patients , 51 in each group , were recruited into the study . There were no significant differences for symptoms of sepsis among groups , except lethargy . No significant differences were observed among the groups according to laboratory data . Overall mortality rate was 8.8 % . The rates of morbidities and mortality among study groups were similar . CONCLUSION PTX and IgM-enriched IVIG therapies , either alone or in combination , did not reduce the rates of morbidities and mortality in NS OBJECTIVE To determine whether therapy with intravenous immunoglobulin G ( IVIG ) would decrease mortality in neonatal sepsis . SETTING Three tertiary care neonatal intensive care units in the city of Bangalore . METHODS All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled . Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded . The neonates were r and omized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo . The rest of the treatment including antibiotics and supportive care was as per the treating physician 's decision . The main outcome variable was survival . RESULTS The trial was carried out over a period of 8 months and recruited 58 neonates . Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group , and one baby who received only one dose of IVIG was excluded from the analysis . Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm . The neonates in the therapy and placebo groups were comparable in terms of birth weight ( 2144+/-675 g vs. 2072+/-682 g ) , gestation ( 37.0+/-3.56 vs. 35.8+/-3.52 weeks ) , sex distribution , duration of stay , and number requiring ventilation . The placebo group had a significantly higher number of babies with positive blood culture . Seven babies in each group died ( p>0.05 ) . There was no significant benefit in using IVIG ( OR 1.0 ; 95 % CI 0.25 - 4.07 ) ( p = 0.74 ) . CONCLUSION In the sample studied therapy with IVIG did not reduce mortality in neonatal The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with neonatal sepsis was evaluated in a prospect i ve r and omized study . All infants received antibiotic therapy and fresh plasma and /or whole blood transfusions . Twenty r and omly-chosen infants were allocated to receive 5 ml/kg/d of IgM-enriched immunoglobulin intravenously for three days . Although the mortality rate in preterm infants whose gestational ages were 31 - 34 weeks in the immunotherapy group was slightly lower than in the control group , the general mortality rate from sepsis in the control group ( 9/24 ) and in the immunotherapy group ( 6/20 ) showed no statistically significant difference ( 37.5 % vs 30.0 % , p < 0.05 ) OBJECTIVE To investigate the effect of rhGM-CSF and rhG-CSF on the monocyte HLA-DR expression of septic neonates . SUBJECTS 60 septic neonates and 41 healthy ones . Septic neonates were r and omly assigned into three treatment groups , the GM-CSF group [ n=20 , rhGM-CSF 5 mcg/kg/d for 4 days , intravenously over 2h ( IV ) ] , the G-CSF group ( n=20 , rhG-CSF 10 mcg/kg/d for 4 days , IV ) and the placebo group ( n=20 , normal saline for 4 days , IV ) . MEASUREMENTS Serial ( days 0,1 , 3 and 5 after the onset of sepsis ) measurements of the percentage of HLA-DR positive monocytes ( % HLA-DR+ monocytes ) and mean fluorescence intensity ( MFI ) by flow-cytometry as well as the absolute monocyte counts ( AMC ) . MAIN RESULTS On day 0 , the HLA-DR expression of the septic neonates ( % HLA-DR+ monocytes : 38%+/-1.8 % ( mean+/-SEM ) and MFI : 73+/-3.4 ) was significantly lower than the healthy control values ( % HLA-DR+ monocytes : 68%+/-2 % and MFI : 123+/-4.6 ) ( P<0.0001 , for both parameters ) . On follow up ( days 1 , 3 and 5 ) , a significant increase of HLA-DR expression was observed in all the groups of septic neonates . Healthy control values of % HLA-DR+ monocytes were reached by day 1 in the GM-CSF group and by day 3 in the G-CSF and placebo groups . Healthy control values of MFI were reached by day 3 in all groups of septic neonates . The AMC showed a significant increase in the GM-CSF group ( during the whole follow up period ) and in the G-CSF group ( for the first 3 days of follow up ) . CONCLUSIONS The monocyte HLA-DR expression is depressed on the onset of neonatal sepsis and is progressively restored during the following days . Treatment with rhGM-CSF results in an earlier increase of the number of monocytes expressing the HLA-DR This study was design ed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would ( 1 ) facilitate neutrophil egress from the marrow , ( 2 ) improve serum opsonic capacity , and ( 3 ) facilitate recovery from the infectious illness . Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin ( IVIG ) per kilogram of body weight or the same volume of a vehicle control ( albumin ) . All 22 infants survived , but significant hematologic , immunologic , and respiratory differences were observed after the IVIG and not after the control infusion . Eleven of the patients had neutropenia ; 24 hours after the infusions , the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients ( p less than 0.001 ) . Ten patients had I/T neutrophil ratios ( a measure of immature neutrophils to total neutrophils on the leukocyte differential count ) of less than 0.2 . One hour after completion of the infusions , all five IVIG recipients had elevated I/T ratios ( mean + /- SEM:0.10 + /- 0.05 before vs 0.43 + /- 0.03 after infusion ; p less than 0.001 ) , suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation ; no increase in the I/T ratio was observed in the control recipients . Six hours after the IVIG infusions , the ratio of arterial oxygen tension to fraction of inspired oxygen increased ; no increase was observed after control infusions . Serum concentrations of IgG , IgG1 , IgG2 , IgG3 , IgG4 , and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects . We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic , hematologic , and physiologic improvement |
2,352 | 24,937,100 | Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity ( BSCVA ) at 12 months postoperatively .
However there is a low risk of developing early cataract with phakic IOLs .
Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia .
Phakic IOL surgery also scored more highly on patient satisfaction/preference question naires .
The results of this review suggest that , at one year post surgery , phakic IOLs are safer than excimer laser surgical correction for moderate to high myopia in the range of -6.0 to -20.0 D and phakic IOLs are preferred by patients .
While phakic IOLs might be accepted clinical practice for higher levels of myopia ( greater than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism ) , it may be worth considering phakic IOL treatment over excimer laser correction for more moderate levels of myopia ( less than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism ) . | BACKGROUND Myopia is a condition in which the focusing power ( refraction ) of the eye is greater than that required for clear distance vision .
There are two main types of surgical correction for moderate to high myopia ; excimer laser and phakic intraocular lenses ( IOLs ) .
Excimer laser refractive surgery for myopia works by removing corneal stroma to lessen the refractive power of the cornea and to bring the image of a viewed object into focus onto the retina rather than in front of it .
Phakic IOLs for the treatment of myopia work by diverging light rays so that the image of a viewed object is brought into focus onto the retina rather than in front of the retina .
They can be placed either in the anterior chamber of the eye in front of the iris or in the posterior chamber of the eye between the iris and the natural lens .
OBJECTIVES To compare excimer laser refractive surgery and phakic IOLs for the correction of moderate to high myopia by evaluating postoperative uncorrected visual acuity , refractive outcome , potential loss of best spectacle corrected visual acuity ( BSCVA ) and the incidence of adverse outcomes . | PURPOSE Evaluation of night glare after excimer laser in situ keratomileusis ( LASIK ) using two different ablation zone diameters . METHODS One hundred and twenty eyes of 60 consecutive myopic patients received LASIK with the Nidek EC-5000 excimer laser . Eyes were r and omized so that every patient had a single ablation zone of 5.5 mm on one eye and an ablation zone of 5.5 mm with a transition zone of 1.0 mm diameter larger on the other eye . Night glare was measured by two methods ; a spot light test and a subjective question naire . RESULTS At 6 months , 54 patients ( 90 % ) were examined ; results of the spot light test showed that 40 patients ( 74.1 % ) perceived more glare with the eye with the single ablation zone ; the subjective question naire indicated that 22 patients ( 40.7 % ) had more night glare with the eye with a single ablation zone compared to the other eye . The use of the transition zone increased the required total ablation depth by 20 % . CONCLUSION The use of a peripheral transition 1.0 mm diameter larger than the ablation zone significantly decreased night glare after LASIK with slight increase in the required central ablation depth OBJECTIVE To compare refractive performance and safety of laser in situ keratomileusis ( LASIK ) and Artisan phakic intraocular lens ( PIOL ) for moderately high myopia . DESIGN A prospect i ve , r and omized trial with paired eye control . PARTICIPANTS Twenty-five patients with myopia ranging from -8.00 to -12.00 diopters ( D ) . INTERVENTION For each patient , one eye received LASIK and the other one was implanted with an Artisan phakic intraocular lens . The treated eye and the surgical technique were r and omized . MAIN OUTCOME MEASURES Primary outcome measure was spherical equivalent refraction . Main secondary outcome measures were the change of two or more lines and safety index ( ratio postoperative to preoperative best-corrected visual acuity ) . RESULTS One year after surgery , the mean spherical equivalent refraction was -0.74 + /- 0.67 D for LASIK-treated eyes and -0.95 + /- 0.45 D for Artisan-treated eyes , and the majority of LASIK-treated eyes ( 64 % ) and Artisan-treated eyes ( 60 % ) were within + /-1.00 D of the intended result . At 1 month , the mean spherical equivalent refraction was -0.28 + /- 0.71 D for LASIK and -1.07 + /- 0.59 D for Artisan ( P < 0.01 ) . The changes of two or more lines were in favor of Artisan ( P < 0.05 ) . The safety index was significantly better for Artisan ( 1.12 + /- 0.21 ) than for LASIK ( 0.99 + /- 0.17 ) at 1 year ( P < 0.02 ) . CONCLUSIONS In cases of moderately high myopia , LASIK and Artisan phakic intraocular lenses seemed to produce a similar predictability . The best-corrected visual acuity and subjective evaluation of quality of vision were better for Artisan Purpose . To compare the results of laser assisted in situ keratomileusis ( LASIK ) and implantable contact lenses ( ICL ) in the correction of moderate/high myopia . Methods . Five hundred fifty-nine LASIK eyes from the Davis Duehr Eye Center , Madison , WI , and 210 ICL eyes from the 14-site U.S. FDA Clinical Trial for ICL for Myopia were compared . These series were concurrently operated on with 8 to 12 D of preoperative myopia and were examined at 1 day , 1 week , 1 month , 6 months , and 1 year postoperatively . The mean baseline myopia was slightly higher in the ICL group , ( ICL : −9.8 ± 1.7 D ; LASIK : −9.1 ± 0.97 D ) . BSCVA , UCVA , and refractions were collected prospect ively in both series . Results . Every index of BSCVA , UCVA , predictability of refraction , and stability of refraction studied favored the ICL over the LASIK procedure . All but one of the indices ( UCVA % 20/40 or better ) were statistically significant in at least half of the time periods studied . At 6-month follow-up , both the loss of two or more lines ( ICL : 0 % ; LASIK : 2%;p = 0.05 ) and gain of two or more lines ( ICL : 7 % ; LASIK : 3%;p = 0.04 ) of BSCVA were better with the ICL . Similarly , efficacy outcomes with the ICL were better with predictability ( attempted versus achieved ±1.0 D ) of the ICL at 90 % ; 76 % with LASIK ( p < 0.001 ) . In this highly myopic series , UCVA 20/20 or better was 50 % with ICL compared with 35 % with LASIK ( p < 0.001 ) . No serious complications occurred in either series of cases . Conclusions . The ICL was safer and more effective than LASIK and appears to be a viable alternative to corneal refractive excimer surgery in the treatment of moderate to high myopia OBJECTIVE To determine the incidence and severity of complications from laser in situ keratomileusis ( LASIK ) for the correction of myopia by experienced and inexperienced surgeons . DESIGN Prospect i ve , observational clinical study . PARTICIPANTS Fourteen surgeons and 1062 eyes of 574 myopic patients who desired surgical correction of myopia ranging from -2.00 to -22.50 diopters ( D ; mean , -7.57 D ) and astigmatism no greater than 4.00 D participated in this study . INTERVENTION Myopia was corrected with LASIK . Astigmatism was corrected with arcuate keratotomy at the same time as the initial procedure or subsequently . MAIN OUTCOME MEASURES Primary outcome measures were change in best spectacle-corrected visual acuity ( BSCVA ) and the incidence of complications . RESULTS Eyes were followed for a mean of 9.5 months after their last surgical procedure ( range , 2 weeks-21 months ) . Three hundred eighty-one eyes ( 36 % ) underwent 468 enhancement procedures 3 months or more after the initial treatment . There were 27 ( 2.1 % ) intraoperative and 40 ( 3.1 % ) postoperative complications . Laser ablation was not performed during the initial treatment of 17 ( 1.6 % ) eyes because of intraoperative complications . Seventy-four eyes gained 2 or more lines of BSCVA , while 50 eyes lost 2 or more lines of BSCVA . Only three eyes lost two or more lines of BSCVA to a level worse than 20/40 . One eye with a flap buttonhole ( BSCVA 20/50 ) also had an epiretinal membrane . The second eye ( BSCVA 20/60 ) had a flap buttonhole that may have been related to a previous corneal transplant . The third eye ( -22.50 D before surgery ) had a rhegmatogenous retinal detachment develop , reducing BSCVA from 20/60 to 20/200 . The incidence of intraoperative complications decreased from 3.1 % during the first 3 months to 0.7 % during the last 9 months of the study ( P = 0.02 ) . CONCLUSIONS LASIK is acceptably safe for the correction of myopia . Although complications occur in approximately 5 % of cases , these rarely lead to visual loss of more than two Snellen lines and postoperative acuity below 20/40 . Flap buttonholes were more likely to cause loss of BSCVA than free or incomplete flaps ( P = 0.02 ) ; flap buttonholes may be more likely in eyes that have undergone previous surgery . Complication rates can be reduced as the surgical team gains experience OBJECTIVE This study evaluated the predictability , stability , and safety of laser in situ keratomileusis ( LASIK ) in myopia and myopic astigmatism . DESIGN The study design was a prospect i ve , unmasked , nonr and omized clinical trial . PARTICIPANTS Participating were 25 patients with myopia ( 37 eyes ) with astigmatism of less than 1.00 diopter ( D ) , divided into 3 subgroups ( -5.00 to -9.90 D , 8 eyes ; -10.00 to -14.90 D , 10 eyes ; -15.00 to -29.00 D , 19 eyes ) , and 37 patients with myopia ( 56 eyes ) with corneal astigmatism of 1.00 to 4.50 D , divided into 3 subgroups ( -5.00 to -9.90 D , 12 eyes ; -10.00 to -14.90 D , 24 eyes ; -15.00 to -29.00 D , 20 eyes ) . INTERVENTION LASIK was performed using the Automatic Corneal Shaper and the Keracor 116 excimer laser . MAIN OUTCOME MEASURES Visual acuity , manifest refraction , central corneal isl and s , ablation decentration , and patient satisfaction were measured . RESULTS At 12 months , predictability , regression between 1 and 12 months , uncorrected visual acuity ( UCVA ) , loss of two or more lines of corrected visual acuity , and patient satisfaction of the spherical ( toric ) groups are reported . Subgroups -5.00 to -9.90 D : 100 % ( 75 % ) + 1.00 D ; regression less than or equal to 1.00 D in 100 % ( 91.7 % ) ; UCVA greater than or equal to 20/40 in 87.5 % ( 70 % ) ; none lost two or more lines ; 100 % ( 84 % ) highly satisfied . Subgroups -10.00 to -14.90 D : 60 % ( 78.3 % ) + /-1.00 D ; regression less than or equal to 1.00 D in 100 % ( 87 % ) ; UCVA greater than or equal to 20/40 in 77.8 % ( 86.4 % ) ; 10 % ( 4.3 % ) lost two lines ; 90 % ( 91 % ) highly satisfied . Subgroups -15.00 to -29.00 D : 38.9 % ( 21.4 % ) + /-1.00 D ; regression less than or equal to 1.00 D in 72.2 % ( 64.3 % ) ; UCVA greater than or equal to 20/40 in 33.3 % ( 40 % ) ; 5.6 % ( 7.1 % ) lost two lines ; 78 % ( 50 % ) highly satisfied . Differences of predictability and change of manifest refraction between subgroups of -5.00 to -9.90 D and -15.00 to -29.00 D were statistically significant . Central isl and s ( decentrations ) were observed in 17 % ( 5.6 % ) of eyes of the spherical and in 16 % ( 4.1 % ) of the toric group . Overall , the corneal interface was visible in 8.2 % . CONCLUSIONS The LASIK method used in this study showed stability of manifest refraction and adequate uncorrected central visual acuity in a large percentage of patients with myopia up to -15.00 D. Corneal stability was not as uniform . Central corneal isl and s were observed in a sizable minority of patients despite pretreatment . For myopia greater than 15.00 D , accuracy and patient satisfaction were sufficiently poor to advise against using the authors ' treatment technique in these groups . Visually significant microkeratome and laser-related problems were noted in a smaller percentage of patients . Patients with astigmatism correction were less pleased with results than were patients who received spherical corrections PURPOSE To compare visual , refractive , and clinical outcomes of foldable iris-fixated phakic intraocular lens ( PIOL ) implantation versus femtosecond laser-assisted LASIK for myopia between -6.00 and -9.00 diopters ( D ) . METHODS Forty-six myopic patients were r and omized to undergo bilateral Artiflex ( Ophtec BV ) PIOL implantation or bilateral femtosecond laser-assisted conventional LASIK with the VISX S2 ( Abbott Medical Optics ) . Refraction , uncorrected ( UDVA ) and corrected ( CDVA ) distance visual acuity , contrast sensitivity , corneal endothelial cell count , rate of retreatment , and complications were compared . RESULTS Twelve months after surgery , no statistically significant differences were noted in spherical equivalent refraction ( P=.19 ) or UDVA ( P=.28 ) , whereas CDVA was better in the PIOL group ( P<.001 ) . Spherical equivalent refraction was within ±0.50 D in 42 ( 91.3 % ) LASIK eyes and 41 ( 89.1 % ) PIOL eyes ( P>.99 ) . The percentage of eyes gaining lines of CDVA was significantly higher in the PIOL group ( 50.0 % vs 8.7 % ; P<.001 ) . Contrast sensitivity was better for PIOL eyes at 1.5 cycles per degree ( cpd ) ( P=.03 ) and 6 cpd ( P=.008 ) . The LASIK eyes showed a mean endothelial cell count increase of 3.7%±2.8 % , whereas PIOL eyes showed a mean decrease of 9.1%±2.0 % ( P<.001 ) . The rate of retreatment was similar ( P=.37 ) , and no serious complications occurred in either group . CONCLUSIONS The Artiflex PIOL provided better CDVA and contrast sensitivity at high spatial frequencies than femtosecond laser-assisted conventional LASIK , suggesting that PIOL implantation is a reasonable option for myopia between -6.00 and -9.00 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 ) PURPOSE To determine the epidemiology of refractive errors in an adult Chinese population in Singapore . METHODS A disproportionate , stratified , clustered , r and om-sampling procedure was used to select names of 2000 Chinese people aged 40 to 79 years from the 1996 Singapore electoral register in the Tanjong Pagar district in Singapore . These people were invited to a central ized clinic for a comprehensive eye examination , including refraction . Refraction was also performed on nonrespondents in their homes . Myopia , high myopia , and hyperopia were defined as a spherical equivalent ( SE ) in the right eye of less than -0.5 D , less than -5.0 D , and more than + 0.5 D , respectively . Astigmatism was defined as less than -0.5 D of cylinder . Anisometropia was defined as a difference in SE of more than 1.0 D between the two eyes . Only phakic eyes were analyzed . RESULTS From 1717 eligible people , 1232 ( 71.8 % ) were examined . Adjusted to the 1997 Singapore population , the overall prevalence of myopia , hyperopia , astigmatism , and anisometropia was 38.7 % ( 95 % confidence interval [ CI ] : 35.5 , 42.1 ) , 28.4 % ( 95 % CI : 25.3 , 31.3 ) , 37.8 % ( 95 % CI : 34.6 , 41.1 ) , and 15.9 % ( 95 % CI : 13.5 , 18.4 ) , respectively . The prevalence of high myopia was 9.1 % ( 95 % CI : 7.2 , 11.2 ) , with women having significantly higher rates than men . The age pattern of myopia was bimodal , with higher prevalence in the 40 to 49 and 70 to 81 age groups and lower prevalence between those age ranges . Prevalence was reversed in hyperopia , with a higher prevalence in subjects aged 50 to 69 . There was a monotonic increase in prevalence with age for both astigmatism and anisometropia . Increasing educational levels , higher individual income , professional or office-related occupations , better housing , and greater severity of nuclear opacity were all significantly associated with higher rates of myopia , after adjustment for age and sex . CONCLUSIONS The results indicate that whereas myopia is 1.5 to 2.5 times more prevalent in adult Chinese residing in Singapore than in similarly aged European-derived population s in the United States and Australia , the sociodemographic associations are similar PURPOSE To compare the Visian Toric Implantable Collamer Lens ( TICL ) , a toric phakic intraocular lens ( IOL ) , and photorefractive keratectomy ( PRK ) in the correction of moderate to high myopic astigmatism . METHODS This prospect i ve , r and omized study consisted of 43 eyes implanted with the TICL ( 20 bilateral cases ) and 45 eyes receiving PRK with mitomycin C ( 22 bilateral cases ) with moderate to high myopia ( -6.00 to -20.00 diopters [ D ] sphere ) measured at the spectacle plane and 1.00 to 4.00 D of astigmatism . All patient treatment and follow-up occurred at the Naval Medical Center San Diego . Study follow-up was 1 day , 1 week , 1 , 3 , 6 , and 12 months postoperative . RESULTS Mean best spectacle-corrected visual acuity ( BSCVA ) , change in BSCVA , proportion of cases with improvement of 1 or more lines of BSCVA , proportion of cases with BSCVA and uncorrected visual acuity ( UCVA ) 20/12.5 or better , proportion of cases with BSCVA and UCVA 20/16 or better ( 6 months , 88 % vs 54 % , P=.002 ) , and predictability + /-1.00 D ( 6 months , 100 % vs 67 % , P<.001 ) were all significantly better in the TICL group than the PRK group at all time periods studied postoperatively . Similarly , contrast sensitivity , tested at both the 5 % photopic level and the 25 % mesopic level , was significantly better at all postoperative time points in the TICL group . Mean spherical equivalent refraction was closer to emmetropia ( 0.28+/-0.41 vs 0.76+/-0.86 , P=.005 ) , and predictability + /-0.50 D and stability of manifest refraction ( + /-0.50 D and + /-1.00 D ) were significantly better in the TICL group at all postoperative visits through 6 months . Mean astigmatism correction at 6 months was not significantly different between the two groups ( 0.52+/-0.33 vs 0.46+/-0.35 , P=.450 ) . CONCLUSIONS The TICL performed better than PRK in all measures of safety ( BSCVA ) , efficacy ( UCVA ) , predictability , and stability in this comparison , supporting the TICL as a viable alternative to existing refractive surgical treatments OBJECTIVE To compare Artisan lens implantation with laser in situ keratomileusis ( LASIK ) for the correction of myopia between -9.00 and -19.50 diopters . DESIGN Prospect i ve r and omized clinical trial . PARTICIPANTS Ninety eyes of 61 consecutive patients were enrolled in the study . INTERVENTION Forty-five eyes ( 50 % ) received Artisan lens , and 45 eyes ( 50 % ) received LASIK ; the procedure assigned to each eye was r and omized . Eighteen patients ( 29.5 % ) received Artisan lens in one eye and LASIK in the other . MAIN OUTCOME MEASURES Slit-lamp microscopy , manifest refraction , uncorrected and spectacle-corrected visual acuity , contrast sensitivity , and specular microscopy were performed before surgery , and 1 , 3 , 6 , and 12 months after surgery . Patient satisfaction and preference were assessed by a subjective question naire . RESULTS At 1 year , 43 eyes ( 95.6 % ) from the Artisan group and 41 eyes ( 91.1 % ) from the LASIK group were examined , the mean spherical equivalent refraction was -0.64 + /- 0.8 diopter in the Artisan eyes and -0.87 + /- 0.8 in the LASIK eyes . The uncorrected visual acuity was 20/20 or better in 9 Artisan eyes ( 20.9 % ) and 5 LASIK eyes ( 12.2 % ) and 20/40 or better in 38 Artisan eyes ( 88.4 % ) and 24 LASIK eyes ( 58.5 % ) ; no Artisan eyes and 5 LASIK eyes ( 12.2 % ) lost 2 or more Snellen lines of spectacle-corrected visual acuity . One Artisan eye ( 2.3 % ) and six LASIK eyes ( 14.6 % ) reported severe night glare ; the Artisan lens was exchanged with a larger optic diameter lens . Mean endothelial cell loss at 1 year was 0.7 + /- 1.1 cells/mm(2 ) in the Artisan eyes and 0.3 + /- 0.9 cells/mm(2 ) in the LASIK eyes . Contrast sensitivity curve decreased by 2 or more lines in two Artisan ( 4.7 % ) and six LASIK eyes ( 14.6 % ) . Of the 18 patients who received both surgeries , one in each eye , 13 patients ( 72.2 % ) preferred the Artisan procedure because of the better quality of vision . CONCLUSIONS In this study , Artisan lens implantation and LASIK were found to be similarly effective , stable , and reasonably safe for the correction of myopia between -9.00 and -19.50 diopters . Better uncorrected and spectacle-corrected visual acuity and contrast sensitivity , a lower enhancement rate , and exchangeability are the main advantages of Artisan lens implantation . Thirteen ( 72.2 % ) of the 18 patients who received the Artisan lens in one eye and LASIK in the other preferred the Artisan lens to the LASIK , mainly because of the better quality of vision |
2,353 | 32,259,791 | The present study showed that IGF-1 serum concentrations are altered by exercise type , but in conditions which are not well-defined .
The systematic review and meta- analysis suggest that there is no determinant in serum IGF-1 changes for the exercise load characteristic .
Therefore , physical exercise may be an alternative treatment to control changes in IGF-1 metabolism and blood concentration | BACKGROUND Physical exercise plays an important role in metabolic health , especially in the insulin-like growth factor-1 ( IGF-1 ) system .
The objective of this study was to perform a systematic review and meta- analysis to evaluate the effects of a single endurance and resistance exercise session on IGF-1 serum . | We examined gender differences in growth hormone ( GH ) secretion during rest and exercise . Eighteen subjects ( 9 women and 9 men ) were tested on two occasions each [ resting condition ( R ) and exercise condition ( Ex ) ] . Blood was sample d at 10-min intervals from 0600 to 1200 and was assayed for GH by chemiluminescence . At R , women had a 3.69-fold greater mean calculated mass of GH secreted per burst compared with men ( 5.4 + /- 1.0 vs. 1.7 + /- 0.4 microg/l , respectively ) and higher basal ( interpulse ) GH secretion rates , which result ed in greater GH production rates and serum GH area under the curve ( AUC ; 1,107 + /- 194 vs. 595 + /- 146 microg x l(-1 ) x min , women vs. men ; P = 0.04 ) . Compared with R , Ex result ed in greater mean mass of GH secreted per burst , greater mean GH secretory burst amplitude , and greater GH AUC ( 1,196 + /- 211 vs. 506 + /- 90 microg x l(-1 ) x min , Ex vs. R , respectively ; P < 0.001 ) . During Ex , women attained maximal serum GH concentrations significantly earlier than men ( 24 vs. 32 min after initiation of Ex , respectively ; P = 0.004 ) . Despite this temporal disparity , both genders had similar maximal serum GH concentrations . The change in AUC ( adjusted for unequal baselines ) was similar for men and women ( 593 + /- 201 vs. 811 + /- 268 microg x l(-1 ) x min ) , but there were significant gender-by-condition interactive effects on GH secretory burst mass , pulsatile GH production rate , and maximal serum GH concentration . We conclude that , although women exhibit greater absolute GH secretion rates than men both at rest and during exercise , exercise evokes a similar incremental GH response in men and women . Thus the magnitude of the incremental secretory GH response is not gender dependent INTRODUCTION This study examined the effects of short-term physical training on the acute hormonal response ( i.e. , growth hormone , total and free insulin-like growth factor I [ IGF-I ] , and IGF binding proteins [IGFBP]-1 , IGFBP-2 , and IGFBP-3 ) to resistance exercise ( RE ) in women . METHODS Forty-six women ( 20.3 ± 0.3 yr , mass = 64.1 ± 7.3 kg , height = 165.7 ± 1.0 cm ) were r and omly assigned to an endurance training ( E ) , resistance training ( R ) , combined training ( R + E ) , or control ( C ) group for 8wk . Subjects completed a st and ardized bout of RE ( six sets of back squats at 10 repetition maximum ) before and after training . Blood sample s were obtained at rest ( PRE ) , after the third set , immediately postexercise ( POST ) , and at 15 min and 30 min after exercise . RESULTS Acute RE significantly increased ( P < 0.05 ) serum growth hormone ( mean ± SD ; change from PRE to POST = + 10.9 ± 7.5 μg·L-1 ) , total IGF-I ( + 66.1 ± 25.4 μg·L-1 ) , IGFBP-1 ( + 2.5 ± 3.1 μg·L-1 ) , IGFBP-2 ( + 86.0 ± 86.8 μg·L-1 ) , and IGFBP-3 ( + 0.69 ± 0.25 mg·L-1 ) concentrations and decreased free IGF-I concentrations ( -0.14 ± 0.21 μg·L-1 ) . After 8 wk of training , total IGF-I concentrations were significantly increased ( change in POST concentrations from week 0 to week 8 = + 82.5 ± 120.8 μg·L-1 ) , and IGFBP-1 concentrations were significantly decreased ( -6.7 ± 13.6 μg·L-1 ) during exercise in groups that participated in resistance training ( R and R + E ) ; no significant changes were seen after E or C. CONCLUSIONS Participation in resistance training increased total IGF-I and reduced IGFBP-1 concentrations during acute RE , indicating exercise mode-specific adaptations in the circulating IGF-I system We examined the relationship between physical fitness and circulating components of the GH-insulin-like growth factor I ( IGF-I ) system [ i.e. GH , GH-binding protein ( GHBP ) , IGF-I , and IGF-binding proteins 1 - 5 ( IGFBP-1 through-5 ) ] in adolescent females ( age range , 15 - 17 yr ) . The study consisted of 1 ) a cross-sectional protocol ( n = 23 ) in which GH-IGF-I components were correlated with fitness , as estimated by thigh muscle volume and maximal O2 uptake ; and 2 ) a prospect i ve study in which fitness , GH-IGF-I system components , and osteocalcin were examined before and after a 5-week period of endurance-type training ( control , n = 6 ; trained , n = 10 ) . The cross-sectional analysis revealed significant ( P < 0.05 ) positive correlations between fitness and 1 ) mean 12-h overnight GH levels , 2 ) GHBP , and 3 ) IGF-I. Muscle volume was negatively correlated with both IGFBP-2 and -4 . The prospect i ve training study was associated with 1 ) increases in circulating osteocalcin ( 39 + /- 14 % ; P < 0.007 ) , and 2 ) decreases in IGF-I ( -14 + /- 5 % ; P < 0.05 ) and IGFBP-5 ( -10 + /- 4 % ; P < 0.04 ) . Unexpectedly , IGFBP-3 fell in both control (-8 + /- 2 % ; P < 0.01 ) and trained subjects ( -5 + /- 3 % ; P < 0.05 ) , and GHBP was reduced only among control subjects ( -10 + /- 7 % ; P < 0.04 ) . In summary , fitter adolescent girls tended to have increased mean serum GH , GHBP , and IGF-I. In contrast , brief endurance training led to increases in muscle mass and serum osteocalcin that were not accompanied by increases in GH or IGF-I. In fact , training may , in the short term , have led to a catabolic state hormonally expressed by reductions in IGF-I and IGFBP-5 The purpose of this study was to determine the impact of dietary factors and exercise-associated factors on the response of IGF-I and its binding proteins ( IGFBPs ) during a period of increased physical activity . Twenty-nine men completed a 4-day ( days 1 - 4 ) baseline period of a controlled energy balanced diet while maintaining their normal physical activity level followed by 7 days ( days 5 - 11 ) of a 1,000 kcal/day increase in physical activity above their normal activity levels . Two subject groups , one sedentary ( Sed , mean Vo(2peak ) : 39 mlxkg(-1)xmin(-1 ) , n = 7 ) and one fit ( FIT1 , mean Vo(2peak ) : 56 ml.kg(-1)xmin(-1 ) , n = 8) increased energy intake to maintain energy balance throughout the 7-day intervention . In two other fit subject groups ( FIT2 , n = 7 and FIT3 , n = 7 ) , energy intake remained at baseline result ing in a 1,000 kcal/day exercise-induced energy deficit . Of these , FIT2 received an adequate protein diet ( 0.9 g/kg ) , and FIT3 received a high-protein diet ( 1.8 g/kg ) . For all four groups , IGF-I , IGFBP-3 , and the acid labile subunit ( ALS ) were significantly decreased by day 11 ( 27 + /- 4 % , 10 + /- 2 % , and 19 + /- 4 % , respectively ) and IGFBP-2 significantly increased by 49 + /- 21 % following day 3 . IGFBP-1 significantly increased only in the two negative energy balance groups , FIT2 ( 38 + /- 6 % ) and FIT3 ( 46 + /- 8 % ) . Differences in initial fitness level and dietary protein intake did not alter the IGF-I system response to an acute increase in physical activity . Decreases in IGF-I were observed during a moderate increase in physical activity despite maintaining energy balance , suggesting that currently unexplained exercise-associated mechanisms , such as increased energy flux , regulate IGF-I independent of energy deficit OBJECTIVE To study interstitial IGF-I concentrations in resting and exercising skeletal muscle in relation to the circulating components of the IGF-IGF binding protein ( IGFBP ) system . DESIGN AND METHODS Seven women performed endurance exercise with 1 leg ( Ex-leg ) for 1 h. The resting leg ( Rest-leg ) served as a control . IGF-I was determined in microdialysate ( MD ) and was compared with veno-arterial ( v-a ) concentrations of circulating IGF-IGFBP components . RESULTS Median ( range ) basal MD-IGF-I was 0.87 ( 0.4 - 1.5 ) microg/l or 0.4 (0.2)% of total-IGF-I ( t-IGF-I ) determined in arterial serum and in the same concentration range as free dissociable IGF-I ( f-IGF-I ) . Rest-leg MD-IGF-I decreased , reaching significance after exercise . Ex-leg MD-IGF-I was unchanged during exercise and declined after exercise at the level of significance ( P = 0.05 ) . There was a release of f-IGF-I from the Ex-leg into the circulation at the end of and shortly after exercise . A small but significant increase in circulating IGFBP-1 was detected at the end of exercise and IGFBP-1 increased further after exercise . Although interleukin-6 ( IL-6 ) has been associated with IGFBP-3 proteolysis , the circulating molecular forms of IGFBP-3 remained unchanged in spite of an IL-6 release from the muscle compartment . CONCLUSIONS Circulating IGFBP-1 is related to interstitial IGF-I in resting muscle although the temporal relationship may not be simple . Further studies should explore the role of local release of IGF-I and its impact on IGF-I activity during contraction Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone ( GH ) concentrations ; however , their combined effect is controversial . The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine , GH , GH secretagogues , and IGF-1 in strength trained participants . Fourteen strength trained males ( age : 25 ± 4 y ; body mass : 81.4 ± 9.0 kg ; height : 179.4 ± 6.9 cm ; and training experience : 6.3 ± 3.4 y ) participated in a r and omized double-blind crossover design ( separated by ~7 days ) . Subjects reported to the laboratory at 08:00 in a fasted state , consumed L-arginine ( ARG ; 0.075 g·kg-1 body mass ) or a placebo ( PLA ) before performing an acute bout of resistance exercise ( 3 sets of 8 exercises , 10 repetitions at ~75 % 1RM ) . Blood sample s were collected at rest , before exercise , and at 0 , 15 , 30 , and 60 min of rest-recovery . The ARG condition significantly increased plasma L-arginine concentrations ( ~120 % ) while no change was detected in the PLA condition . There were no differences between conditions for GH , GH-releasing hormone , ghrelin , or IGF-1 at any time point . GH-inhibiting hormone was significantly lower in the ARG condition . However , integrated area under the curve for GH was blunted in the ARG condition ( L-arginine = 288.4 ± 368.7 vs. placebo = 487.9± 482.0 min·ng·mL1 , p < .05 ) . L-arginine ingested before resistance exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH . Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop Taylor , LW , Wilborn , CD , Kreider , RB , and Willoughby , DS . Effects of resistance exercise intensity on extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activation in men . J Strength Cond Res 26(3 ) : 599–607 , 2012—Extracellular signal-regulated kinase ( ERK ) 1/2 signaling has been shown to be increased after heavy resistance exercise and suggested to play a role in the hypertrophic adaptations that are known to occur with training . However , the role that ERK1/2 may play in response to lower intensities of resistance exercise is unknown . Therefore , the purpose of this study was to determine the effects of resistance exercise intensity on ERK1/2 activity in human skeletal muscle . Twelve recreationally active men completed separate bouts of single-legged resistance exercise with 8–10 repetitions ( reps ) at 80–85 % 1 repetition maximum ( 1RM ) ( 85 % ) and 18–20 reps at 60–65 % 1RM ( 65 % ) in a r and omized crossover fashion . For both resistance exercise sessions , vastus lateralis biopsies and blood draws were taken immediately before exercise ( PRE ) and at 30 minutes ( 30MPST ) , 2 hours ( 2HRPST ) , and 6 hours ( 6HRPST ) post exercise , with an additional blood draw occurring immediately after exercise ( POST ) . The phosphorylated levels of pIGF-1R , pMEK1 , pERK1/2 , and activated Elk-1 were assessed by phosphoELISA , and serum insulin-like growth factor 1 ( IGF-1 ) was assessed via enzyme-linked immunosorbent assay . Statistical analyses used a 2 × 4 ( muscle responses ) and 2 × 5 ( serum responses ) multivariate analysis of variance on delta values from baseline ( p < 0.05 ) . Both exercise intensities significantly increased the activity of insulin-like growth factor 1 receptor ( IGF-1R ) , mitogen-activated protein kinase 1 , ERK1/2 , and Elk-1 , with peak activity occurring at 2HRPST ( p < 0.001 ) . However , 65 % result ed in a preferential increase in IGF-1R and Elk-1 activation when compared with 85 % ( p < 0.05 ) . No differences were observed for serum IGF-1 levels regardless of intensity and time . These findings demonstrate that resistance exercise upregulates ERK1/2 signaling in a manner that does not appear to be preferentially dependent on exercise intensity OBJECTIVE Excess weight has been associated with increased risk of cancer at several organ sites . In part , this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides . The objectives of the study were to examine the association of body mass index ( BMI ) with circulating and rogens ( testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEAS ) ) , estrogens ( estrone and estradiol ) , sex hormone-binding globulin ( SHBG ) , IGF-I and IGF-binding protein (IGFBP)-3 , and the relationship between sex steroids , IGF-I and IGFBP-3 . DESIGN AND METHODS A cross-sectional analysis was performed using hormonal and question naire data of 620 healthy women ( 177 pre- and 443 post-menopausal ) . The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk . RESULTS In the pre-menopausal group , BMI was not related to and rogens and IGF-I. In the post-menopausal group , estrogens , testosterone and and rostenedione increased with increasing BMI . The association with IGF-I was non-linear , with the highest mean concentrations observed in women with BMI between 24 and 25 . In both pre- and post-menopausal subjects , IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI . As for the correlations between peptide and steroid hormones , in the post-menopausal group , IGF-I was positively related to and rogens , inversely correlated with SHBG , and not correlated with estrogens . In the pre-menopausal group , similar but weaker correlations between IGF-I and and rogens were observed . CONCLUSIONS These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation , especially after menopause . Circulating IGF-I , and rogens and SHBG appear to be related to each other in post-menopausal women To investigate the effect of heavy resistance exercise on IGF-1 system , 19 healthy trained men and 15 healthy untrained men volunteered to participate in this study . The subjects were r and omly divided into experimental and control groups . Subjects of experimental groups were forced to perform a heavy resistance exercise with the intensity of 70–80 % of 1RM in selected movements . The blood sample s were taken from all subjects four times ; before ( T1 ) , immediately after ( T2 ) , 5 ( T3 ) , and 8 ( T4 ) hours after exercise . Analysis of data showed that a session of heavy resistance exercise induced significant increase in GH at T2 ( P < 0.05 ) and a significant decrease in insulin at T4 ( P < 0.05 ) and a significant decrease in IGFBP3 at T4 ( P < 0.05 ) in trained group . In untrained group , no significant change in any of the variables was observed . However , the procedure of response in variables was almost similar in two experimental groups . Although , the exercise did not appreciably affect IGF-1 levels , it decreased in all groups at length of time after exercise . In addition , the exercise did not have any notable effect on IGFBP1 levels over time . In conclusion , the findings of this study indicate that the intense resistance exercise can lead to changes in blood concentrations of IGF-1 system components which are observable in blood circulation over time and the amounts of changes depend on subjects ’ fitness levels and exercise variables OBJECTIVE The purpose of this study was to : 1 ) evaluate differential responses of the IGF-I system to either a calisthenic- or resistance exercise-based program and 2 ) determine if this chronic training altered the IGF-I system during an acute resistance exercise protocol . DESIGN Thirty-two volunteers were r and omly assigned into a resistance exercise-based training ( RT ) group ( n=15 , 27±5y , 174±6 cm , 81±12 kg ) or a calisthenic-based training group ( CT ) ( n=17 , 29±5y , 179±8 cm , 85±10 kg ) and all underwent 8weeks of exercise training ( 1.5h/d , 5d/wk ) . Basal blood was sample d pre- ( Week 0 ) , mid- ( Week 4 ) and post-training ( Week 8) and assayed for IGF-I system analytes . An acute resistance exercise protocol ( AREP ) was conducted pre and post-training consisting of 6 sets of 10 repetitions in the squat with two minutes of rest in between sets and the IGF-I system analytes measured . A repeated measures ANOVA ( p≤0.05 ) was used for statistical analysis . RESULTS No interaction or within-subject effects were observed for basal total IGF-I , free IGF-I , or IGFBP-1 . IGFBP-2 ( pre ; 578.6±295.7post-training ; 14.3±1.9μg/mL ; p=0.01 ) . An interaction was observed for the RT group as IGFBP-3 increased from pre to mid ( 3462.4±216.4 vs. 3962.2±227.9ng/mL ) , but was not significant at the post-training time point ( 3770.3±228.7ng/mL ) . AREP caused all analytes except free IGF-I ( 40 % decrease ) to increase ( 17 - 27 % ; p=0.001 ) during exercise , returning to baseline concentration into recovery . CONCLUSION Post-training , bioavailable IGF-I recovered more rapidly post-exercise . 8wks of chronic physical training result ed in increased basal IGFBP-2 and IGFBP-3 , decreased ALS , increased pre-AREP free IGF-I and a more rapid free IGF-I recovery post-AREP . While total IGF-I was insensitive to chronic physical training , changes were observed with circulating IGFBPs and bioavailable IGF-I. To glean the most robust information on the effects of exercise training , studies must move beyond relying solely on total IGF-I measures and should consider IGFBPs and bioavailable IGF-I as these components of the circulating IGF-I system are essential determinants of IGF-I physiological action |
2,354 | 28,938,015 | DISCUSSION We conclude that the effects of several treatments are promising , but need to be replicated before they can be implemented more widely in primary care . | BACKGROUND Late-life depression is most often treated in primary care , and it usually coincides with chronic somatic diseases .
Given that antidepressants contribute to polypharmacy in these patients , and potentially to interactions with other drugs , non-pharmacological treatments are essential .
In this systematic review and meta- analysis , we aim ed to present an overview of the non-pharmacological treatments available in primary care for late-life depression . | Background Depression is a disabling , prevalent condition . Physical activity programs may assist depression management in older people , ameliorate co-morbid conditions and reduce the need for antidepressants . The UPLIFT pilot study assessed the feasibility of older depressed people attending a community-based progressive resistance training ( PRT ) program . The study also aim ed to determine whether PRT improves depressive status in older depressed patients . Methods A r and omised controlled trial was conducted . People aged ≥ 65 years with depressive symptoms were recruited via general practice s. Following baseline assessment , subjects were r and omly allocated to attend a local PRT program three times per week for 10 weeks or a brief advice control group . Follow-up assessment of depressive status , physical and psychological health , functional and quality of life status occurred post intervention and at six months . Results Three hundred and forty six people responded to the study invitation , of whom 22 % had depressive symptoms ( Geriatric Depression Scale , GDS-30 score ≥ 11 ) . Thirty two people entered the trial . There were no significant group differences on the GDS at follow-up . At six months there was a trend for the PRT intervention group to have lower GDS scores than the comparison group , but this finding did not reach significance ( p = 0.08 ) . More of the PRT group ( 57 % ) had a reduction in depressive symptoms post program , compared to 44 % of the control group . It was not possible to discern which specific components of the program influenced its impact , but in post hoc analyses , improvement in depressive status appeared to be associated with the number of exercise sessions completed ( r = -0.8 , p < 0.01 ) . Conclusion The UPLIFT pilot study confirmed that older people with depression can be successfully recruited to a community based PRT program . The program can be offered by existing community-based facilities , enabling its ongoing implementation for the potential benefit of other older people BACKGROUND Although exercise has been shown to relieve depression , little is known about its mechanism or dose-response characteristics . We hypothesized that high intensity progressive resistance training ( PRT ) would be more effective than either low intensity PRT or st and ard care by a general practitioner ( GP ) in depressed elderly persons , and that high intensity PRT would provide superior benefits in quality of life , sleep quality , and self-efficacy . METHODS Sixty community-dwelling adults > 60 years with major or minor depression were r and omized to supervised high intensity PRT ( 80 % maximum load ) or low intensity PRT ( 20 % maximum load ) 3 days per week for 8 weeks , or GP care . RESULTS A 50 % reduction in the Hamilton Rating Scale of Depression score was achieved in 61 % of the high intensity , 29 % of the low intensity , and 21 % of the GP care group ( p = .03 ) . Strength gain was directly associated with reduction in depressive symptoms ( r = 0.40 , p = .004 ) , as was baseline social support network type ( F = 3.52 , p = .015 ) , whereas personality type , self-efficacy , and locus of control were unrelated to the antidepressant effect . Vitality quality -of-life scale improved more in the high intensity group than in the others ( p = .04 ) . Sleep quality improved significantly in all participants ( p < .0001 ) , with the greatest relative change in high intensity PRT ( p = .05 ) . CONCLUSIONS High intensity PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients BACKGROUND Serum anticholinergic activity ( SAA ) , as measured by a radioreceptor assay , quantifies a person 's overall anticholinergic burden caused by all drugs and their metabolites . In several small geriatric patient groups , SAA has been associated with cognitive impairment or frank delirium . To our knowledge , there has not yet been any systematic study of the prevalence of SAA and its effect on cognition in a community-based population . METHODS Serum anticholinergic activity was measured in 201 subjects who were r and omly selected among the participants in an epidemiological community study , based on their age and sex . Cognitive performance was assessed with use of the Mini-Mental State Examination . The association between SAA and cognitive performance was examined using a univariate analysis and a multiple logistic regression model , adjusting for age , sex , educational level , and number of medications . RESULTS Serum anticholinergic activity was detectable in 180 ( 89.6 % ) participants ( range , 0.50 - 5.70 pmol/mL ) . Univariate testing showed a significant association between SAA and Mini-Mental State Examination scores . Logistic regression analysis indicated that subjects with SAA at or above the sample 's 90th percentile ( ie , SAA > /=2.80 pmol/mL ) were 13 times ( odds ratio , 1.08 - 152.39 ) more likely than subjects with undetectable SAA to have a Mini-Mental State Examination score of 24 ( the sample 's 10th percentile ) or below . CONCLUSIONS To our knowledge , this is the largest analysis of SAA and the first to examine its extent and relationship with cognitive performance in a community sample . Its results suggest that SAA can be detected in most older persons in the community and confirm that even low SAA is associated with cognitive impairment BACKGROUND Depression is a major health problem for community-dwelling elderly adults . Since limited re sources are available to decrease the high prevalence of depressive symptoms among the elderly adults , improved support for them can be provided if we can determine which intervention is superior in ridding depressive symptoms . OBJECTIVE To compare the effectiveness of the physical fitness exercise program and the cognitive behavior therapy program on primary ( depressive symptoms ) and secondary outcomes ( 6-min walk distance , quality of life , and social support ) for community-dwelling elderly adults with depressive symptoms . DESIGN AND SETTING S A prospect i ve r and omized control trial was conducted in three communities in northern Taiwan . PARTICIPANTS The elderly adults in the three communities were invited to participate by mail , phone calls , and posters . There were a total of 57 participants who had depressive symptoms and all without impaired cognition that participated in this trial . None of the participants withdrew during the 9 months of follow-up for this study . METHODS Fifty-seven participants were r and omly assigned to one of the three groups : the physical fitness exercise program group , the cognitive behavior therapy ( CBT ) group , or the control group . The primary ( Geriatric Depression Scale-15 , GDS-15 ) , and secondary outcomes ( 6-min walk distance , SF-36 , and Inventory of Socially Supportive Behaviors scales , ISSB ) were collected immediately ( T2 ) , at 3 months ( T3 ) , and at 6 months after the interventions ( T4 ) . RESULTS After the interventions , the CBT group participants demonstrated significantly lower symptoms of depression ( p=0.009 ) at T2 and perceived more social support from those around them ( p<0.001 , < 0.001 and = 0.004 , respectively ) at three time-point comparisons than the control group . Moreover , after intervention , participants in the physical fitness exercise program group had decreased GDS-15 scores at three time-point comparisons ( p=0.003 , 0.012 and 0.037 , respectively ) , had a substantially greater 6-min walk distance ( p=0.023 ) , a better quality of life ( p<0.001 ) , and a better perceived social support at T2 ( p<0.001 ) . CONCLUSIONS Immediately after a 12-week intervention , there were significant decreases in depressive symptoms and more perceived social support amongst those in the CBT group . When considering the effectiveness in the decrease of depressive symptoms longer term , the increase in the 6-min walk distance and raising the patients ' quality of life , physical fitness exercise program may be a better intervention for elderly adults with depressive symptoms Objectives We pilot tested a one-visit behavioral intervention with telephone follow-up for older primary care patients with mild to moderate depressive symptoms . Methods A total of 16 English-speaking primary care patients aged 60 years and older who scored 5 to 14 on the Patient Health Question naire-9 ( PHQ-9 ) engaged in the intervention visit . Outcomes were assessed at baseline and 4 weeks : activity goals , readiness to change ( University of Rhode Isl and Change Assessment ) , PHQ-9 , Generalized Anxiety Disorder-7 , World Health Organization Disability Assessment Schedule 2.0 , and satisfaction . Results The 14 participants who completed the study met or exceeded 73 % of activity goals on average . They also improved on all outcomes ( P < 0.05 ) with medium ( University of Rhode Isl and Change Assessment , GAD-7 ) to large effect sizes ( PHQ-9 , World Health Organization Disability Assessment Schedule 2.0 ) , and they were satisfied . Conclusions This pilot study provided preliminary evidence that a one-visit behavioral activation intervention is acceptable and feasible and improves outcomes . If findings are confirmed , then this intervention could be integrated into existing collaborative care programs OBJECTIVES This study provides an empirical evaluation of Cognitive Behaviour Therapy ( CBT ) alone vs Treatment as usual ( TAU ) alone ( generally pharmacotherapy ) for late life depression in a UK primary care setting . METHOD General Practitioners in Fife and Glasgow referred 114 Participants to the study with 44 meeting inclusion criteria and 40 participants providing data that permitted analysis . All participants had a diagnosis of mild to moderate Major Depressive Episode . Participants were r and omly allocated to receive either TAU alone or CBT alone . RESULTS Participants in both treatment conditions benefited from treatment with reduced scores on primary measures of mood at end of treatment and at 6 months follow-up from the end of treatment . When adjusting for differences in baseline scores , gender and living arrangements , CBT may be beneficial in levels of hopelessness at 6 months follow-up . When evaluating outcome in terms of numbers of participants meeting Research Diagnostic Criteria for depression , there were significant differences favouring the CBT condition at the end of treatment and at 3 months follow-up after treatment . CONCLUSIONS CBT alone and TAU alone produced significant reductions in depressive symptoms at the end of treatment and at 6 months follow-up . CBT on its own is shown to be an effective treatment procedure for mild to moderate late life depression and has utility as a treatment alternative for older people who can not or will not tolerate physical treatment approaches for depression Anxiety and depression are commonly comorbid in older adults and are associated with worse physical and mental health outcomes and poorer response to psychological and pharmacological treatments . However , little research has examined the effectiveness of psychological programs to treat comorbid anxiety and depression in older adults . Sixty-two community dwelling adults aged over 60 years with comorbid anxiety and depression were r and omly allocated to group cognitive behavioural therapy or a waitlist condition and were assessed immediately following and three months after treatment . After controlling for cognitive ability at pre-treatment , cognitive behaviour therapy result ed in significantly greater reductions , than waitlist , on symptoms of anxiety and depression based on a semi-structured diagnostic interview rated by clinicians unaware of treatment condition . Significant time by treatment interactions were also found for self-report measures of anxiety and depression and these gains were maintained at the three month follow up period . In contrast no significant differences were found between groups on measures of worry and well-being . In conclusion , group cognitive behavioural therapy is efficacious in reducing comorbid anxiety and depression in geriatric population s and gains maintain for at least three months CONTEXT In older people , depressive symptoms are common , psychological adjustment to aging is complex , and associated chronic physical illness limits the use of antidepressants . Despite this , older people are rarely offered psychological interventions , and only 3 r and omized controlled trials of individual cognitive behavioral therapy ( CBT ) in a primary care setting have been published . OBJECTIVE To determine the clinical effectiveness of CBT delivered in primary care for older people with depression . DESIGN A single-blind , r and omized , controlled trial with 4- and 10-month follow-up visits . PATIENTS A total of 204 people aged 65 years or older ( mean [ SD ] age , 74.1 [ 7.0 ] years ; 79.4 % female ; 20.6 % male ) with a Geriatric Mental State diagnosis of depression were recruited from primary care . INTERVENTIONS Treatment as usual ( TAU ) , TAU plus a talking control ( TC ) , or TAU plus CBT . The TC and CBT were offered over 4 months . OUTCOME MEASURES Beck Depression Inventory-II ( BDI-II ) scores collected at baseline , end of therapy ( 4 months ) , and 10 months after the baseline visit . Subsidiary measures were the Beck Anxiety Inventory , Social Functioning Question naire , and Euroqol . Intent to treat using Generalized Estimating Equation and Compliance Average Causal Effect analyses were used . RESULTS Eighty percent of participants were followed up . The mean number of sessions of TC or CBT was just greater than 7 . Intent-to-treat analysis found improvements of -3.07 ( 95 % confidence interval [ CI ] , -5.73 to -0.42 ) and -3.65 ( 95 % CI , -6.18 to -1.12 ) in BDI-II scores in favor of CBT vs TAU and TC , respectively . Compliance Average Causal Effect analysis compared CBT with TC . A significant benefit of CBT of 0.4 points ( 95 % CI , 0.01 to 0.72 ) on the BDI-II per therapy session was observed . The cognitive therapy scale showed no difference for nonspecific , but significant differences for specific factors in therapy . Ratings for CBT were high ( mean [ SD ] , 54.2 [ 4.1 ] ) . CONCLUSION Cognitive behavioral therapy is an effective treatment for older people with depressive disorder and appears to be associated with its specific effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N18271323 The purpose of this study was to compare cognitive-behavioral group therapy ( CBGT ) , clinical case management ( CCM ) , and their combination ( CBGT + CCM ) to treat depression in low-income older adults ( 60 + ) . Sixty-seven participants with major depressive disorder or dysthymia were r and omly assigned and entered into 1 of the 3 treatment conditions for 6 months . They were followed for 18 months after treatment initiation on depression and functional outcomes . CCM and CBGT + CCM led to greater improvements in depressive symptoms than CBGT , but CBGT led to greater improvements in physical functioning . All 3 conditions result ed in similar reduction of needs . Findings suggest that disadvantaged older adults with depression benefit from increased access to social services either alone or combined with psychotherapy 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 CONTEXT Major depressive disorder ( MDD ) in elderly individuals is prevalent and debilitating . It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus , the biological clock of the brain . Circadian rhythm disturbances are common in the elderly . Suprachiasmatic nucleus stimulation using bright light treatment ( BLT ) may , therefore , improve mood , sleep , and hormonal rhythms in elderly patients with MDD . OBJECTIVE To determine the efficacy of BLT in elderly patients with MDD . DESIGN Double-blind , placebo-controlled r and omized clinical trial . SETTING Home-based treatment in patients recruited from outpatient clinics and from case-finding using general practitioners ' offices in the Amsterdam region . PARTICIPANTS Eighty-nine out patients 60 years or older who had MDD underwent assessment at baseline ( T0 ) , after 3 weeks of treatment ( T1 ) , and 3 weeks after the end of treatment ( T2 ) . Intervention Three weeks of 1-hour early-morning BLT ( pale blue , approximately 7500 lux ) vs placebo ( dim red light , approximately 50 lux ) . MAIN OUTCOME MEASURES Mean improvement in Hamilton Scale for Depression scores at T1 and T2 using parameters of sleep and cortisol and melatonin levels . RESULTS Intention-to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT more than placebo from T0 to T1 ( 7 % ; 95 % confidence interval , 4%-23 % ; P = .03 ) and from T0 to T2 ( 21 % ; 7%-31 % ; P = .001 ) . At T1 relative to T0 , get-up time after final awakening in the BLT group advanced by 7 % ( P < .001 ) , sleep efficiency increased by 2 % ( P = .01 ) , and the steepness of the rise in evening melatonin levels increased by 81 % ( P = .03 ) compared with the placebo group . At T2 relative to T0 , get-up time was still advanced by 3 % ( P = .001 ) and the 24-hour urinary free cortisol level was 37 % lower ( P = .003 ) compared with the placebo group . The evening salivary cortisol level had decreased by 34 % in the BLT group compared with an increase of 7 % in the placebo group ( P = .02 ) . CONCLUSIONS In elderly patients with MDD , BLT improved mood , enhanced sleep efficiency , and increased the upslope melatonin level gradient . In addition , BLT produced continuing improvement in mood and an attenuation of cortisol hyperexcretion after discontinuation of treatment . TRIAL REGISTRATION clinical trials.gov Identifier NCT00332670 OBJECTIVES Depressive symptoms are common among elderly primary care patients , and because they encounter considerable barriers in seeking help and they often resist referral to specialized mental health facilities , it is important to look for easily accessible interventions within the primary care setting . Bibliotherapy , which has been found to be effective among younger population s , might be an attractive option . In this study , the authors investigated the effectiveness of bibliotherapy for depressive symptomatology in very old adults . DESIGN R and omized controlled trial . After a 3-month period of " watchful waiting , " the participants were r and omly assigned to a bibliotherapy group or a usual care group . SETTING Thirty-three general practice s in the north-western region of the Netherl and s. PARTICIPANTS One hundred seventy community-dwelling adults , aged 75 and older , with subthreshold depression . INTERVENTION The bibliotherapy intervention consisted of an information leaflet and a self-help manual " Coping with Depression " adapted for the elderly . MEASUREMENTS Outcome measures after 3 months were a ) change in depressive symptoms according to the Center for Epidemiologic Studies Depression Scale ( CES-D ) and b ) the proportion of participants who scored a significant improvement on the CES-D. RESULTS One hundred forty-six ( 85.9 % ) of the 170 participants completed the baseline and follow-up measurements . The authors did not find any clinical ly relevant and statistically significant differences between the intervention group and the control group in the severity of the depressive symptoms . CONCLUSION Bibliotherapy as a st and -alone intervention for the elderly ( aged 75 years and older ) did not reduce depressive symptoms more than usual care . This might indicate that bibliotherapy can only be effective for patients who are motivated and acknowledge their depression CONTEXT Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia . OBJECTIVE To compare the effectiveness of pharmacotherapy and psychotherapy in primary care setting s among older persons with minor depression or dysthymia . DESIGN R and omized , placebo-controlled trial ( November 1995-August 1998 ) . SETTING Four geographically and clinical ly diverse primary care practice s. PARTICIPANTS A total of 415 primary care patients ( mean age , 71 years ) with minor depression ( n = 204 ) or dysthymia ( n = 211 ) and a Hamilton Depression Rating Scale ( HDRS ) score of at least 10 were r and omized ; 311 ( 74.9 % ) completed all study visits . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 137 ) or placebo ( n = 140 ) , starting at 10 mg/d and titrated to a maximum of 40 mg/d , or problem-solving treatment- primary care ( PST-PC ; n = 138 ) . For the paroxetine and placebo groups , the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring ; for the PST-PC group , visits were for psychotherapy . MAIN OUTCOME MEASURES Depressive symptoms , by the 20-item Hopkins Symptom Checklist Depression Scale ( HSCL-D-20 ) and the HDRS ; and functional status , by the Medical Outcomes Study Short-Form 36 ( SF-36 ) physical and mental components . RESULTS Paroxetine patients showed greater ( difference in mean [ SE ] 11-week change in HSCL-D-20 scores , 0.21 [ 0 . 07 ] ; P = .004 ) symptom resolution than placebo patients . Patients treated with PST-PC did not show more improvement than placebo ( difference in mean [ SE ] change in HSCL-D-20 scores , 0.11 [ 0.13 ] ; P = .13 ) , but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks ( P = .01 ) . For dysthymia , paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high ( difference in mean [ SE ] change in SF-36 mental component scores , 5.8 [ 2.02 ] ; P = . 01 ) or intermediate ( difference in mean [ SE ] change in SF-36 mental component scores , 4.4 [ 1.74 ] ; P = .03 ) . Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo ( P>/=.12 for low- , intermediate- , and high-functioning groups ) . For minor depression , both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning ( difference vs placebo in mean [ SE ] change in SF-36 mental component scores , 4.7 [ 2.03 ] for those taking paroxetine ; 4.7 [ 1.96 ] for the PST-PC treatment ; P = .02 vs placebo ) . CONCLUSIONS Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression . The benefits of PST-PC were smaller , had slower onset , and were more subject to site differences than those of paroxetine CONTEXT Older adults with social isolation , medical comorbidity , and physical impairment are more likely to be depressed but may be less able to seek appropriate care for depression compared with older adults without these characteristics . OBJECTIVE To determine the effectiveness of a home-based program of detecting and managing minor depression or dysthymia among older adults . DESIGN AND SETTING R and omized controlled trial with recruitment through community senior service agencies in metropolitan Seattle , Wash , from January 2000 to May 2003 . PATIENTS One hundred thirty-eight patients aged 60 years or older with minor depression ( 51.4 % ) or dysthymia ( 48.6 % ) . Patients had a mean of 4.6 ( SD , 2.1 ) chronic medical conditions ; 42 % of the sample belonged to a racial/ethnic minority , 72 % lived alone , 58 % had an annual income of less than 10 000 dollars , and 69 % received a form of home assistance . INTERVENTIONS Patients were r and omly assigned to the Program to Encourage Active , Rewarding Lives for Seniors ( PEARLS ) intervention ( n = 72 ) or usual care ( n = 66 ) . The PEARLS intervention consisted of problem-solving treatment , social and physical activation , and potential recommendations to patients ' physicians regarding antidepressant medications . MAIN OUTCOME MEASURES Assessment s of depression and quality of life at 12 months compared with baseline . RESULTS At 12 months , compared with the usual care group , patients receiving the PEARLS intervention were more likely to have at least a 50 % reduction in depressive symptoms ( 43 % vs 15 % ; odds ratio [ OR ] , 5.21 ; 95 % confidence interval [ CI ] , 2.01 - 13.49 ) , to achieve complete remission from depression ( 36 % vs 12 % ; OR , 4.96 ; 95 % CI , 1.79 - 13.72 ) , and to have greater health-related quality -of-life improvements in functional well-being ( P = .001 ) and emotional well-being ( P = .048 ) . CONCLUSIONS The PEARLS program , a community-integrated , home-based treatment for depression , significantly reduced depressive symptoms and improved health status in chronically medically ill older adults with minor depression and dysthymia UNLABELLED Depression is a common and significant health problem among older adults . Unfortunately , while effective psychological treatments exist , few older adults access treatment . The aim of the present r and omized controlled trial ( RCT ) was to examine the efficacy , long-term outcomes , and cost-effectiveness of a therapist-guided internet-delivered cognitive behavior therapy ( iCBT ) intervention for Australian adults over 60 years of age with symptoms of depression . Participants were r and omly allocated to either a treatment group ( n=29 ) or a delayed-treatment waitlist control group ( n=25 ) . Twenty-seven treatment group participants started the iCBT treatment and 70 % completed the treatment within the 8-week course , with 85 % of participants providing data at posttreatment . Treatment comprised an online 5-lesson iCBT course with brief weekly contact with a clinical psychologist , delivered over 8 weeks . The primary outcome measure was the Patient Health Question naire-9 Item ( PHQ-9 ) , a measure of symptoms and severity of depression . Significantly lower scores on the PHQ-9 ( Cohen 's d=2.08 ; 95 % CI : 1.38 - 2.72 ) and on a measure of anxiety ( Generalized Anxiety Disorder-7 Item ) ( Cohen 's d=1.22 ; 95 % CI : 0.61 - 1.79 ) were observed in the treatment group compared to the control group at posttreatment . The treatment group maintained these lower scores at the 3-month and 12-month follow-up time points and the iCBT treatment was rated as acceptable by participants . The treatment group had slightly higher Quality -Adjusted Life-Years ( QALYs ) than the control group at posttreatment ( estimate : 0.012 ; 95 % CI : 0.004 to 0.020 ) and , while being a higher cost ( estimate $ 52.9l 95 % CI : -23.8 to 128.2 ) , the intervention was cost-effective according to commonly used willingness-to-pay thresholds in Australia . The results support the potential efficacy and cost-effectiveness of therapist-guided iCBT as a treatment for older adults with symptoms of depression . TRIAL REGISTRATION Australian and New Zeal and Clinical Trials Registry : ACTRN12611000927921 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=343384 Background : Among older persons with chronic somatic diseases , depression often remains unrecognized and untreated in primary care . The Depression in Elderly with Long-Term Afflictions ( DELTA ) study aim ed to evaluate the effectiveness of a nurse-led minimal psychological intervention ( MPI ) in chronically ill elderly persons with depression . Methods : A r and omized controlled trial was conducted , comparing the MPI with usual care in 361 primary care patients . Four nurses had an average of 4 sessions with the intervention patients , each lasting 1 h , over a maximum period of 3 months . Patients were aged 60 years and older , had a minor depression or mild-to-moderate major depression , and either had type II diabetes or chronic obstructive pulmonary disease . Results : Nine months after the intervention , patients receiving the MPI had significantly fewer depressive symptoms ; the intervention patients were also more likely than usual-care controls to show a ≧50 % reduction in depressive symptoms relative to baseline values . At 9 months , diabetic MPI patients had a better quality of life than diabetic controls . Conclusions : The nurse-led MPI appears to be a feasible and moderately effective method of managing minor-to-moderate depression in chronically ill elderly persons . However , we can not rule out attention-placebo effects , and the disappointing finding of a recent economic evaluation showing only a 63 % chance of the MPI being cost-effective . From a clinical point of view , however , it is of interest to further evaluate adaptations of the MPI , with a stronger emphasis on detection , watchful waiting and mental health problems in general OBJECTIVES This preliminary study examines the efficacy of 12-week home-delivered problem adaptation therapy ( PATH ) versus home-delivered supportive therapy ( ST ) in reducing depression and disability in 30 depressed , cognitively impaired , disabled older adults . DESIGN A 12-week r and omized clinical trial . Research assistants were unaware of the participants ' r and omization status . Assessment s were conducted at baseline , 6 weeks , and 12 weeks . SETTING Weill-Cornell Advanced Center for Interventions and Services Research . PARTICIPANTS Thirty elders with major depression , cognitive impairment , and disability were recruited through advertisement and the Home-Delivered Meals Program of the Westchester County Department of Senior Programs and Services . INTERVENTION PATH is a home-delivered intervention design ed to reduce depression and disability in depressed , cognitively impaired , disabled elders . PATH is based on problem-solving therapy and integrates environmental adaptation and caregiver participation . PATH is consistent with Lawton 's ecologic model of adaptive functioning in aging . MEASUREMENTS Depression and disability were measured with Hamilton Depression Rating Scale-24 items and Sheehan Disability Scale , respectively . Client Satisfaction Question naire was used to assess patient satisfaction with treatment . RESULTS Mixed-effects model analyses revealed that PATH was more efficacious than ST in reducing depression and disability at 12 weeks . Participants in both treatment groups were satisfied with treatment . CONCLUSIONS This preliminary study suggests that PATH is well accepted and efficacious in depressed elders with major depression , cognitive impairment , and disability . Because this population may not adequately respond to antidepressant medication treatment , PATH may provide relief to many patients who would otherwise remain depressed and continue to suffer BACKGROUND Depression in elderly people may be contributed to by the multiple losses of aging . Exercise has the potential to positively impact many of these losses simultaneously . We tested the hypothesis that progressive resistance training ( PRT ) would reduce depression while improving physiologic capacity , quality of life , morale , function and self-efficacy without adverse events in an older , significantly depressed population . METHODS We conducted a 10-week r and omized controlled trial of volunteers aged 60 and above with major or minor depression or dysthymia . Subjects were r and omized for 10 weeks to either a supervised PRT program three times a week or an attention-control group . RESULTS A total of 32 subjects aged 60 - 84 , mean age 71.3 + /- 1.2 yr , were r and omized and completed the study . No significant adverse events occurred . Median compliance was 95 % . PRT significantly reduced all depression measures ( Beck Depression Inventory in exercisers 21.3 + /- 1.8 to 9.8 + /- 2.4 versus controls 18.4 + /- 1.7 to 13.8 + /- 2 , p = .002 ; Hamilton Rating Scale of Depression in exercisers 12.3 + /- 0.9 to 5.3 + /- 1.3 versus controls 11.4 + /- 1.0 to 8.9 + /- 1.3 , p = .008 ) . Quality of life subscales of bodily pain ( p = .001 ) , vitality ( p = .002 ) , social functioning ( p = .008 ) , and role emotional ( p = .02 ) were all significantly improved by exercise compared to controls . Strength increased a mean of 33 % + /- 4 % in exercisers and decreased 2 % + /- 2 % in controls ( p < .0001 ) . In a multiple stepwise regression model , intensity of training was a significant independent predictor of decrease in depression scores ( r2 = .617 , p = .0002 ) . CONCLUSIONS PRT is an effective antidepressant in depressed elders , while also improving strength , morale , and quality of life BACKGROUND Little is known about the prevalence of depression in older patients consulting their general practitioner . AIM To estimate the prevalence of major and minor depression in older GP attendees . DESIGN Cross sectional two-stage screening design . SETTING Seventeen GPs in urban and 41 GPs in rural setting s. METHODS Data of The West Friesl and Study were used . Five thous and , six hundred and eight-six GP attendees of 55 years and older filled in the Geriatric Depression Scale-15 items as a screening instrument for depression ( response 62 % ) . Of those screened positive on the GDS-15 , 846 ( 77.5 % ) were interviewed using the Primary Care Evaluation of Mental Disorders ( PRIME-MD ) . A r and om sample ( n = 102 ) scoring below the threshold of the GDS-15 was interviewed to estimate the proportion of false negatives . RESULTS Major depression was prevalent in 13.7 % and minor depression in 10.2 % of the patients . Depressed patients were older ( mean difference 0.7 years ; p = 0.037 ) , more often female ( OR 1.3 ; p < 0.001 ) and lived more often in urban districts ( OR 1.5 ; p < 0.001 ) . Patients with major depression were younger ( mean difference 1.9 years ; p < 0.001 ) and more often female ( OR 1.4 ; p = 0.026 ) than those with a minor depression . Only 22.9 % of the patients with a major depression were treated with antidepressants . CONCLUSION Depression in older GP attendees is a very common health problem . Further research should focus on identifying those groups of patients with high risk of persistence of depression . This could help to focus the limited re sources available in general practice to those patients in whom treatment is most urgently needed IMPORTANCE Problem adaptation therapy ( PATH ) is a treatment for older adults with major depression , cognitive impairment ( from mild cognitive deficits to moderate dementia ) , and disability . Antidepressants have limited efficacy in this population and psychosocial interventions are inadequately investigated . OBJECTIVE To test the efficacy of 12-week PATH vs supportive therapy for cognitively impaired patients ( ST-CI ) in reducing depression and disability in 74 older adults with major depression , cognitive impairment , and disability . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial at the Weill Cornell Institute of Geriatric Psychiatry from April 1 , 2006 , to September 31 , 2011 . Interventions were administered at the participants ' homes . Participants included 74 older individuals ( age ≥ 65 years ) with major depression and cognitive impairment to the level of moderate dementia . They were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry and were r and omly assigned to 12 weekly sessions of PATH or ST-CI ( 14.8 % attrition rate ) . INTERVENTIONS Home-delivered PATH vs home-delivered ST-CI . Problem adaptation therapy integrates a problem-solving approach with compensatory strategies , environmental adaptations , and caregiver participation to improve patients ' emotion regulation . Supportive therapy for cognitively impaired patients focuses on expression of affect , underst and ing , and empathy . MAIN OUTCOMES AND MEASURES Mixed-effects models for longitudinal data compared the efficacy of PATH with that of ST-CI in reducing depression ( Montgomery-Asberg Depression Rating Scale ) and disability ( World Health Organization Disability Assessment Schedule II ) during 12 weeks of treatment . RESULTS Participants in PATH had significantly greater reduction in depression ( Cohen d , 0.60 ; 95 % CI , 0.13 - 1.06 ; treatment × time , F(1,179 ) = 8.03 ; P = .005 ) and disability ( Cohen d , 0.67 ; 95 % CI , 0.20 - 1.14 ; treatment × time , F(1,169 ) = 14.86 ; P = .001 ) than ST-CI participants during the 12-week period ( primary outcomes ) . Furthermore , PATH participants had significantly greater depression remission rates than ST-CI participants ( 37.84 % vs 13.51 % ; χ(2 ) = 5.74 ; P = .02 ; number needed to treat = 4.11 ) ( secondary outcome ) . CONCLUSIONS AND RELEVANCE Problem adaptation therapy was more efficacious than ST-CI in reducing depression and disability . Problem adaptation therapy may provide relief to a large group of depressed and cognitively impaired older adults who have few treatment options . TRIALS REGISTRATION Clinical trials.gov Identifier : NCT00368940 Increasing evidence from experimental studies and human observations suggests that drugs with anticholinergic properties can cause physical and mental impairment . The aim of this study was to evaluate the relationship between the use of drugs with anticholinergic activity and measures of physical performance , muscle strength , and functional status in persons aged 80 years or older . Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study . The ilSIRENTE study is a prospect i ve cohort study performed in the mountain community living in the Sirente geographic area ( L'Aquila , Abruzzo ) in Central Italy . Physical performance was assessed using the physical performance battery score ( Short Physical Performance Battery ) , which is based on three timed tests : 4‐meter walking speed , balance , and chair st and tests . Muscle strength was measured by h and grip strength . We defined as anticholinergic drugs all medications for which serum anticholinergic activity was previously demonstrated . Analyses of covariance were performed to evaluate the relationship of anticholinergic drugs with physical function . In the unadjusted model , all the physical performance , muscle strength , and functional measures showed significant associations with the anticholinergic drug use . After adjustment for potential confounders ( age , gender , smoking , physical activity level , cognitive performance score , living alone , body mass index , congestive heart failure , lung diseases , diabetes ) , these associations were weaker but still statistically significant ( physical performance battery score : non‐users anticholinergic drugs 6.9 , SE 0.1 , users anticholinergic drugs 6.1 , SE 0.2 , P=0.05 ; h and grip strength : non‐users anticholinergic drugs 31.3 kg , SE 0.8 , users anticholinergic drugs 28.8 kg , SE 1.0 , P=0.05 ; Activities of Daily Living scale score : non‐users anticholinergic drugs 1.2 , SE 0.1 , users anticholinergic drugs 1.6 , SE 0.1 , P=0.03 ; Instrumental Activities of Daily Living scale score : non‐users anticholinergic drugs 2.7 , SE 0.1 , users anticholinergic drugs 3.4 , SE 0.1 , P<0.001 ) . The use of medication with anticholinergic properties is common among community older subjects in Italy . Our results suggest that among old‐old subjects the use of anticholinergic drugs is associated with impaired physical performance and functional status This study examined the stability of treatment gains after receiving either cognitive bibliotherapy or individual cognitive psychotherapy for depression in older adults . A 2-year follow-up of 23 participants from Floyd , Scogin , McKendree-Smith , Floyd , and Rokke ( 2004 ) was conducted by comparing pre- and posttreatment scores with follow-up scores on the Hamilton Rating Scale for Depression ( HRSD ) and the Geriatric Depression Scale ( GDS ) . Results indicated that treatment gains from baseline to the 2-year follow-up period were maintained on the HRSD and GDS , and there was not a significant decline from posttreatment to follow-up . There were no significant differences between the treatments on the GDS or HRSD at the 2-year follow-up ; however , bibliotherapy participants had significantly more recurrences of depression during the follow-up period The aim of this study was to examine the efficacy of life review based on autobiographical retrieval practice for treating depressed older adults . Forty-three adults aged 65 - 93 with clinical ly significant depressive symptomatology and no dementia were r and omly assigned to treatment or to no treatment . The results indicated significant differences between experimental and control groups after 4 weeks of autobiographical retrieval practice . At posttest , those in the treatment condition showed fewer depressive symptoms , less hopelessness , improved life satisfaction , and retrieval of more specific events . The findings suggest that practice in autobiographical memory for specific events may be among the components of life review that account for its effectiveness and could be a useful tool in psychotherapy with older adults Life- review therapy has been recognized as an effective therapeutic approach for depression in older adults . Additionally , the use of new media is becoming increasingly common in psychological interventions . The aim of this study was to investigate a life- review therapy in a face-to-face setting with additional computer use . This study explored whether a six-week life- review therapy with computer supplements from the e-mental health Butler system constitutes an effective approach to treat depression in older adults aged 65 and over . A total of 36 participants with elevated levels of depressive symptoms were r and omized to a treatment group or a waiting-list control group and completed the post- assessment . Fourteen individuals in the intervention group completed the follow-up assessment . Analyses revealed significant changes from pre- to post-treatment or follow-up for depression , well-being , self-esteem , and obsessive reminiscence , but not for integrative reminiscence and life satisfaction . Depressive symptoms decreased significantly over time until the three-month follow-up in the intervention group compared to the control group ( pre to post : d = 1.13 ; pre to follow-up : d = 1.27 ; and group × time effect pre to post : d = 0.72 ) . Furthermore , the therapy led to an increase in well-being and a decrease in obsessive reminiscence among the participants in the intervention group from pre-treatment to follow-up ( well-being : d = 0.70 ; obsessive reminiscence : d = 0.93 ) . Analyses further revealed a significant but small group × time effect regarding self-esteem ( d = 0.19 ) . By and large , the results indicate that the life- review therapy in this combined setting could be recommended for depressive older adults The efficacy of bibliotherapy for mildly and moderately depressed older adults was examined . Cognitive bibliotherapy and behavioral bibliotherapy were compared with a delayed-treatment control condition . Results indicate that the two experimental conditions were superior to the control condition , but that the cognitive and behavioral bibliotherapies were nondifferentially efficacious . Sixty-six percent of the subjects demonstrated clinical ly significant change . There were no specific effects associated with either the cognitive or the behavioral interventions . Treatment gains were maintained at 6-month follow-up . The implication s of bibliotherapy for geriatric depression as an alternative or adjunct to traditional treatments are discussed Thirty community-dwelling , moderately depressed elderly were r and omly assigned to 1 of 3 interventions : experimenter-accompanied exercise in the form of walking , a social contact control condition , and a wait-list control . Exercise and social contact both result ed in significant reductions in both the total and the psychological subscale of the Beck Depression Inventory ( BDI ) . The exercise condition , however , unlike the control conditions , result ed in decreased somatic symptoms of the BDI . These results indicate that , at least in the short term , exercise has a broader effect compared with control conditions in reducing depressive symptoms in the moderately depressed elderly There is little evidence to support the efficacy of the life storybook creation process , which incorporates the use of narratives , in mediating depression levels . The study aim ed to examine the effects of the life storybook creation process on depressive symptoms among older community-dwelling Chinese adults in Singapore . A r and omised controlled trial was conducted from January 2011 to March 2012 . Twenty-six Chinese aged over 60 years , who were able to communicate in Chinese and /or English , and with mild to severe depression were r and omly allocated to either the life storybook ( intervention ) group ( n = 14 ) or the non-life storybook ( control ) group ( n = 12 ) . Subjects in the intervention group were interviewed on a one to one basis on five sessions over 8 weeks . Depressive symptoms were measured using the Geriatric Depression Scale . Generalised estimating equations were used to examine the effects of the intervention on the elderly peoples ' depression level . Significant reductions in depression scores were found in the intervention group from baseline ( mean 7.9 [ SD 3.0 ] ) to week 8 ( 2.5 [ 1.7 ] , χ(2 ) = 15.25 , P < 0.001 ) . At week 8 , the intervention group showed a lower level of depression than the control ( χ(2 ) = 4.33 , P = 0.037 ) . This study supports the life storybook creation process as an effective intervention for depressed older Chinese adults living in the community . The findings suggest that this intervention may enhance the quality of care provided by healthcare providers as the therapeutic relationship between provider and client is being established OBJECTIVES Subsyndromal depression ( SSD ) is several times more common than major depression in older adults and is associated with significant negative health outcomes . Physical activity can improve depression , but adherence is often poor . The authors assessed the feasibility , acceptability , and short-term efficacy and safety of a novel intervention using exergames ( entertaining video games that combine game play with exercise ) for SSD in older adults . METHODS Community-dwelling older adults ( N = 19 , aged 63 - 94 years ) with SSD participated in a 12-week pilot study ( with follow-up at 20 - 24 weeks ) of Nintendo 's Wii sports , with three 35-minute sessions a week . RESULTS Eight-six percent of enrolled participants completed the 12-week intervention . There was a significant improvement in depressive symptoms , mental health-related quality of life ( QoL ) , and cognitive performance but not physical health-related QoL. There were no major adverse events , and improvement in depression was maintained at follow-up . CONCLUSIONS The findings provide preliminary indication of the benefits of exergames in seniors with SSD . R and omized controlled trials of exergames for late-life SSD are warranted This study investigated behavioral activation ( BA ) bibliotherapy as a treatment for late-life depressive symptoms . BA bibliotherapy was administered using Addis and Martell 's Overcoming depression one step at a time as a st and -alone treatment that was completed by participants ( N = 26 ) over a 4-week period [ Addis , M.E. , & Martell , C.R. ( 2004 ) . Overcoming depression one step at a time . Oakl and , CA : New Harbinger Publications , Inc. ] . Results of an immediate intervention group were compared with those of a delayed treatment control group and treatment response for both groups was evaluated at 1-month follow-up . Primary outcome results showed that symptoms on a clinician-rated measure of depressive symptoms , Hamilton Rating Scale for Depression , were significantly lower at post-treatment for those who received immediate BA bibliotherapy compared with those who were in the delayed treatment control condition . However , self-reported depressive symptoms ( a secondary outcome measured via the Geriatric Depression Scale ) , were not significantly different at this period . Because study control was lost after the delayed treatment group received the intervention , within-subjects analyses examining both treatment groups combined showed that clinician-rated depressive symptoms significantly decreased from pre-treatment to both post-treatment and 1-month follow-up . Self-reported depressive symptoms were significantly lower from pre-treatment to 1-month follow-up . These findings suggest that BA may be useful in treating mild or subthreshold depressive symptoms in an older adult population Background Depressive symptoms are common in older adults . The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited . A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable . Behavioural Activation ( BA ) protocol s are less complicated and more easy to train than other psychological therapies , making them very suitable for delivery by less specialised therapists . The recent introduction of the mental health nurse in primary care centres in the Netherl and s has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care . BA may thus address the needs of older patients while improving treatment outcome and lowering costs . The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual ( TAU ) for late-life depression in Dutch primary care . A secondary goal is to explore several potential mechanisms of change , as well as predictors and moderators of treatment outcome of BA for late-life depression . Methods / design Cluster-r and omised controlled multicentre trial with two parallel groups : a ) behavioural activation , and b ) treatment as usual , conducted in primary care centres with a follow-up of 52 weeks . The main inclusion criterion is a PHQ-9 score > 9 . Patients are excluded from the trial in case of severe mental illness that requires specialized treatment , high suicide risk , drug and /or alcohol abuse , prior psychotherapy , change in dosage or type of prescribed antidepressants in the previous 12 weeks , or moderate to severe cognitive impairment . The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse . Discussion We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU . BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care . Trial registration This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013 on August 25th 2016 |
2,355 | 29,672,201 | Conclusions Greater practitioner empathy or communication of positive messages can have small patient benefits for a range of clinical conditions , especially pain . | Background Practitioners who enhance how they express empathy and create positive expectations of benefit could improve patient outcomes .
However , the evidence in this area has not been recently synthesis ed .
Objective To estimate the effects of empathy and expectations interventions for any clinical condition . | A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were r and omly selected for one of four consultations : a consultation conducted in a " positive manner , " with and without treatment , and a consultation conducted in a " non-positive manner , " called a negative consultation , with and without treatment . Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups . Similarly , 64 % of those receiving a positive consultation got better , compared with 39 % of those who received a negative consultation ( p = 0.001 ) and 53 % of those treated got better compared with 50 % of those not treated ( p = 0.5 ) Summary This multifactorial mixed‐ methods r and omized controlled trial quantified the specific and nonspecific factors of acupuncture , and found that the practitioner , not the treatment , has the strongest effect on outcome . Abstract The nonspecific effects of acupuncture are well documented ; we wished to quantify these factors in osteoarthritic ( OA ) pain , examining needling , the consultation , and the practitioner . In a prospect i ve r and omised , single‐blind , placebo‐controlled , multifactorial , mixed‐ methods trial , 221 patients with OA awaiting joint replacement surgery were recruited . Interventions were acupuncture , Streitberger placebo acupuncture , and mock electrical stimulation , each with empathic or nonempathic consultations . Interventions involved eight 30‐minute treatments over 4 weeks . The primary outcome was pain ( VAS ) at 1 week posttreatment . Face‐to‐face qualitative interviews were conducted ( purposive sample , 27 participants ) . Improvements occurred from baseline for all interventions with no significant differences between real and placebo acupuncture ( mean difference −2.7 mm , 95 % confidence intervals −9.0 to 3.6 ; P = .40 ) or mock stimulation ( −3.9 , −10.4 to 2.7 ; P = .25 ) . Empathic consultations did not affect pain ( 3.0 mm , −2.2 to 8.2 ; P = .26 ) but practitioner 3 achieved greater analgesia than practitioner 2 ( 10.9 , 3.9 to 18.0 ; P = .002 ) . Qualitative analysis indicated that patients ’ beliefs about treatment veracity and confidence in outcomes were reciprocally linked . The supportive nature of the trial attenuated differences between the different consultation styles . Improvements occurred from baseline , but acupuncture has no specific efficacy over either placebo . The individual practitioner and the patient ’s belief had a significant effect on outcome . The 2 placebos were equally as effective and credible as acupuncture . Needle and nonneedle placebos are equivalent . An unknown characteristic of the treating practitioner predicts outcome , as does the patient ’s belief ( independently ) . Beliefs about treatment veracity shape how patients self‐report outcome , complicating and confounding study interpretation OBJECTIVE To examine the causal effects of doctor-patient relations and the severity of a medical outcome on medical patient perceptions and mal practice intentions in the event of an adverse medical outcome . DESIGN R and omized between-subjects experimental design . Patients were given scenarios depicting interactions between an obstetric patient and her physician throughout the patient 's pregnancy , labor , and delivery . PARTICIPANTS One hundred twenty-eight postpartum obstetric patients were approached for participation , of whom 104 completed the study . Main outcome measures Patients ' perceptions of physician competence and intentions to file a mal practice cl aim . RESULTS Positive physician communication behaviors increased patients ' perceptions of physician competence and decreased mal practice cl aim intentions toward both the physician and the hospital . A more severe outcome increased only patients ' intentions to sue the hospital . CONCLUSION These results provide empiric evidence for a direct , causal effect of the doctor-patient relationship on medical patients ' treatment perceptions and mal practice cl aim intentions in the event of an adverse medical outcome Background Placebo effects contribute substantially to outcome in most fields of medicine . While clinical trials typically try to control or minimize these effects , the potential of placebo mechanisms to improve outcome is rarely used . Patient expectations about treatment efficacy and outcome are major mechanisms that contribute to these placebo effects . We aim ed to optimize these expectations to improve outcome in patients undergoing coronary artery bypass graft ( CABG ) surgery . Methods In a prospect i ve three-arm r and omized clinical trial with a 6 month follow-up , 124 patients scheduled for CABG surgery were r and omized to either a brief psychological pre-surgery intervention to optimize outcome expectations ( EXPECT ) ; or a psychological control intervention focusing on emotional support and general advice , but not on expectations ( SUPPORT ) ; or to st and ard medical care ( SMC ) . Interventions were kept brief to be feasible with a heart surgery environment ; “ dose ” of therapy was identical for both pre-surgery interventions . Primary outcome was disability 6 months after surgery . Secondary outcomes comprised further clinical and immunological variables . Results Patients in the EXPECT group showed significantly larger improvements in disability ( −12.6 ; −17.6 to −7.5 ) than the SMC group ( −1.9 ; −6.6 to + 2.7 ) ; patients in the SUPPORT group ( −6.7 ; −11.8 to 1.7 ) did not differ from the SMC group . Comparing follow-up scores and controlling for baseline scores of EXPECT versus SUPPORT on the variable disability only revealed a trend in favor of the EXPECT group ( P = 0.09 ) . Specific advantages for EXPECT compared to SUPPORT were found for mental quality of life and fitness for work ( hours per week ) . Both psychological pre-surgery interventions induced less pronounced increases in pro-inflammatory cytokine concentrations reflected by decreased interleukin-8 levels post-surgery compared to changes in SMC patients and lower interleukin-6 levels in patients of the EXPECT group at follow-up . Both pre-surgery interventions were characterized by great patient acceptability and no adverse effects were attributed to them . Considering the innovative nature of this approach , replication in larger , multicenter trials is needed . Conclusions Optimizing patients ’ expectations pre-surgery helps to improve outcome 6 months after treatment . This implies that making use of placebo mechanisms has the potential to improve long-term outcome of highly invasive medical interventions . Further studies are warranted to generalize this approach to other fields of medicine . Trial registration Ethical approval for the study was obtained from the IRB of the Medical School , University of Marburg , and the trial was registered at ( NCT01407055 ) on July 25 , 2011 Variations in treatment effects between drug trials are usually attributed to different patient characteristics , variations in outcome assessment , and r and om error . We have previously hypothesized that part of the variation in treatment effects between drug trials might be caused by differences in nonspecific factors . In a r and omized clinical trial , we aim ed to investigate whether experimentally induced expectancy can modify the analgesic effect of tramadol relative to placebo in chronic pain patients . In a 2 x 2 factorial , r and omized , placebo-controlled , double-blind trial , chronic pain patients attending a chronic pain outpatient clinic were r and omized to receive a single oral dose of 50 mg tramadol or placebo , and they were further r and omized to receive positive or neutral information , verbally expressed by the physician , regarding the expected analgesic effect of the drug . Pain intensity was measured using a 10 centimeter visual analogue scale at baseline , and 0.5 , 1 , 2 , 4 , 6 , and 8 hours after baseline . The one-hour pain intensity difference , calculated as the sum of pain intensity differences between baseline and 0.5 and 1 hour , was taken as main outcome measure . The one-hour sum of pain intensity differences of 28 patients treated after positive expectation and r and omized to tramadol was 1.4 cm , while in 27 patients r and omized to placebo , it was 0.8 cm . This corresponds with an analgesic effect of tramadol relative to placebo of 0.6 cm ( 95 % confidence interval [ CI ] , -0.5 cm to 1.8 cm ) . The 28 patients in the neutral expectancy group who were r and omized to tramadol reported a 1.4 cm decrease on the sum of pain intensity differences , while 28 patients in the placebo group reported a 0.9 cm decrease . This corresponds with an analgesic effect of tramadol relative to placebo of 0.5 cm ( 95 % CI , -0.9 cm to 1.8 cm ) . The 0.1 cm difference ( 0.6 cm - 0.5 cm ) in analgesic effect between positive and neutral expectancy group was not statistically significant ( 95 % CI , -0.7 cm to 1.0 cm ) . This trial did not discern a significant difference in the analgesic effect of tramadol between a positive and neutral expectancy group . This means that the phenomenon either does not exist , or we had an inappropriate model to demonstrate it . Regardless , this study demonstrates the type of quality trial that should be done to find out which non-specific factors , such as information regarding the expected effect , can modify treatment effects BACKGROUND Clinicians frequently warn patients of discomfort before potentially painful procedures , despite the lack of evidence that such communications are helpful . We aim ed to compare two communications ( one with , and the other without , a warning of a ' sting ' ) immediately before i.v . cannulation in order to measure differences in perceived pain by patients during the procedure . METHODS R and omly assigned patients awaiting elective surgery received a communication immediately before i.v . cannulation consisting of either ' I am going to apply the tourniquet and insert the needle in a few moments . It 's a sharp scratch and it may sting a little ' ( Group S ) or ' I am going to apply the tourniquet on the arm . As I do this many people find the arm becomes heavy , numb and tingly . This allows the drip to be placed more comfortably ' ( Group NS ) . Cannulation pain was measured by a 0 - 10 verbal numerical rating score ( VNRS ) and five-point Likert scale . RESULTS Of 101 participants , 49 were allocated to Group S and 52 to Group NS . Median VNRS pain scores with inter-quartile ranges ( IQR ) were 1 and 2 , respectively , for both groups . Median Likert scores were 3 in Group S and 2 in Group NS with an IQR of 1 for both groups ( P = 0.13 ) . Six participants vocalized pain in Group S and none in Group NS ( P = 0.01 ) . Three participants withdrew their arm spontaneously in Group S and none in Group NS ( P = 0.11 ) . CONCLUSIONS Warning patients of a ' sting ' before i.v . cannulation may not be helpful BACKGROUND The impact of changing non-verbal consultation behaviours is unknown . AIM To assess brief physician training on improving predominantly non-verbal communication . DESIGN AND SETTING Cluster r and omised parallel group trial among adults aged ≥16 years attending general practice s close to the study coordinating centres in Southampton . METHOD Sixteen GPs were r and omised to no training , or training consisting of a brief presentation of behaviours identified from a prior study ( acronym KEPe Warm : demonstrating Knowledge of the patient ; Encouraging [ back-channelling by saying ' hmm ' , for example ] ; Physically engaging [ touch , gestures , slight lean ] ; Warm-up : cool/professional initially , warming up , avoiding distancing or non-verbal cut-offs at the end of the consultation ) ; and encouragement to reflect on videos of their consultation . Outcomes were the Medical Interview Satisfaction Scale ( MISS ) mean item score ( 1 - 7 ) and patients ' perceptions of other domains of communication . RESULTS Intervention participants scored higher MISS overall ( 0.23 , 95 % confidence interval [ CI ] = 0.06 to 0.41 ) , with the largest changes in the distress-relief and perceived relationship subscales . Significant improvement occurred in perceived communication/partnership ( 0.29 , 95 % CI = 0.09 to 0.49 ) and health promotion ( 0.26 , 95 % CI = 0.05 to 0.46 ) . Non-significant improvements occurred in perceptions of a personal relationship , a positive approach , and underst and ing the effects of the illness on life . CONCLUSION Brief training of GPs in predominantly non-verbal communication in the consultation and reflection on consultation videotapes improves patients ' perceptions of satisfaction , distress , a partnership approach , and health promotion BACKGROUND Placebos are hypothesized to exert positive effects on medical conditions by enhancing patient expectancies . Recent review s suggest that placebo benefits are restricted to subjective responses , like pain , but might be ineffective for objective physiologic outcomes . Nevertheless , mind-body links and placebo responsivity in asthma are widely believed to exist . OBJECTIVE We carried out a r and omized , double-blind investigation to ( 1 ) determine whether placebo can suppress airway hyperreactivity in asthmatic subjects , ( 2 ) quantify the placebo effect , ( 3 ) identify predictors of the placebo response , and ( 4 ) determine whether physician interventions modify the placebo response . METHODS In a double-blind , crossover design investigation , 55 subjects with mild intermittent and persistent asthma with stable airway hyperreactivity were r and omized to placebo or salmeterol before serial methacholine challenges . Subjects were additionally r and omized to physician interactions that communicated either positive or neutral expectancies regarding drug effect . RESULTS Placebo bronchodilator administration significantly reduced bronchial hyperreactivity compared with baseline ( the calculated concentration of methacholine required to induce a 20 % decrease in FEV(1 ) nearly doubled ) ; 18 % of subjects were placebo responders by using conservative definitions . Experimental manipulation of physician behavior altered perceptions of the physician but not the magnitude or frequency of the placebo response . CONCLUSIONS Objective placebo effects exist in asthma . These responses are of significant magnitude and likely to be meaningful clinical ly . The placebo response was not modulated by alterations in physician behavior in this study . CLINICAL IMPLICATION S The placebo response in patients with asthma is important in underst and ing the limitations of clinical research studies and in maximizing safe and effective therapies . This article confirms the existence of a strong placebo response in an objective and clinical ly relevant measure of disease activity Common practice during local anesthetic injection is to warn the patient using words such as : “ You will feel a big bee sting ; this is the worst part . ” Our hypothesis was that using gentler words for administration of the local anesthetic improves pain perception and patient comfort . One hundred forty healthy women at term gestation requesting neuraxial analgesia were r and omized to either a “ placebo ” ( “ We are going to give you a local anesthetic that will numb the area and you will be comfortable during the procedure ” ) or “ nocebo ” ( “ You are going to feel a big bee sting ; this is the worst part of the procedure ” ) group . Pain was assessed immediately after the local anesthetic skin injection using verbal analog scale scores of 0 to 10 . Median verbal analog scale pain scores were lower when reassuring words were used compared with the harsher nocebo words ( 3 [ 2–4 ] vs 5 [ 3–6 ] ; P < 0.001 ) . Our data suggest that using gentler , more reassuring words improves the subjective experience during invasive procedures Abstract To examine the potential role for a placebo cream in reducing reported needle pain severity in children , and the impact of age‐related factors on pain self‐report , a convenience sample of 117 children scheduled for venipuncture were r and omly assigned to one of three treatments : ( a ) placebo cream with the suggestion that it might help reduce needle pain , ( b ) placebo cream with no indication as to the cream 's purpose , and ( c ) no cream ( control group ) . In allocation to treatment , children were stratified by age group , ( 3–7 , 8–11 , 12–17 years ) . They rated their needle pain severity ( both predicted and reported ) using the Faces Pain Scale , and rated their anxiety about the procedure using the Children 's Anxiety and Pain Scale . Children in the cream groups were also asked whether they thought the cream had helped . Using video‐tapes , an independent observer , blind to the placebo manipulation , rated each child 's reaction to the needle . For the two groups receiving cream , 83 % of those children told it might help stated that they believed it did , as compared with only 33 % of children who received the cream but were told nothing of its purpose . These beliefs , however , were not reflected in self‐report ratings of pain which showed no statistically significant treatment effect . Similarly , children who gave higher preprocedural anxiety ratings were no more likely to report less pain as a result of receiving the cream . There was , however , a treatment effect on the observer 's ratings : children receiving cream plus suggestion were assigned significantly lower ratings of pain‐related behaviour than those children who received the cream alone . While venipuncture was associated with only mild levels of pain , younger children , irrespective of treatment group , did report more pain than older children . Hierarchical regression analysis indicated that 60 % of the variance in self‐reported pain severity scores could be accounted for by how much the child thought the needle would hurt , how anxious the child was about receiving the needle , gender ( higher pain ratings associated with girls ) , and estimated body surface area ( higher pain ratings associated with smaller bodies ) . We conclude that the efficacy of placebo treatments for needle pain in children may depend on the suggestion of a possible benefit rather than upon treatment application per se BACKGROUND The perception of pain is germane to the environmental stimuli . Nurses on surgical wards are the main contributor in influencing patients ' psychophysiological fettle . The aim of the study was to investigate the effect of different words , negative or positive , from nurses on postoperative pain therapy with patient-controlled analgesia ( PCA ) . METHODS 1500 ASA I-II patients , who underwent abdominal hysterectomy , were screened and 771 were r and omized into one of four groups . In the no words group ( NW , N.=35 ) , no words was delivered . The positive ( PW , N.=248 ) , partially negative ( NW1 , N.=241 ) and totally negative ( NW2 , N.=247 ) groups received corresponding words when treating with morphine PCA , the words were given singly at the 3(rd ) , 6(th ) , 12(th ) , 18(th ) h and repeatedly at the 3(rd ) and 6(th ) h , and each group was redivided into six subgroups according to varying time points . Pain intensity , morphine consumption , side effects , overall sedation and satisfaction scores were recorded and plasma cortisol was tested . RESULTS A total of 614 patients completed the study . Negative words expressed significant influence on pain therapy at the 3(rd ) and 6(th ) h after surgeries ( P<0.01 ) , and this effect was more convenient in repeatedly treated patients ( P<0.001 ) . Positive and the 12(th ) and 18(th ) h negative words displayed little role in pain management . Morphine consumption , side effects , satisfaction and cortisol level converted with the change of the pain intensity . No intergroup differences were observed in patients ' overall conditions . CONCLUSION Negative words on surgical wards influenced postoperative pain management at the earlier period of time after abdominal surgeries associated with the HPA axis activation OBJECTIVE To evaluate the effects of a short interactive training program for general practitioners ( GP ) on pain management in patients with osteoarthritis ( OA ) . METHODS A multicenter , parallel-group study . GP were r and omized to receive training on relationships and communication , pain evaluation , prescription , and negotiation of a patient contract or to a control group receiving a presentation about obtaining consent in trials . Outcomes were patient assessment s of pain and functional ability . We invited 1500 GP to take part in the study . Those who volunteered to receive the training recruited out patients from May 2001 to April 2002 . Patients participating in the evaluation of the effects of the general practitioners ' training had lower limb OA and pain on motion [ > or = 40 mm on a visual analog scale ( VAS ) ] and had indications for treatment with acetaminophen . The primary endpoint : sum of patient pain relief based on the daily VAS self-evaluation during the 2 weeks of the trial . RESULTS In total , 180 GP ( 84 trained , 96 nontrained ) enrolled 842 patients ( 414 and 428 , respectively ) . Mean baseline VAS pain was 63 + /- 14 mm . Patients in the trained-GP group had better overall pain relief ( 316 + /- 290 mm/day vs 265 + /- 243 mm ; p < 0.0001 ) , greater improvement in Lequesne and WOMAC scores ( p < 0.0001 ) , and better overall perception of treatment ( p = 0.002 ) . Acetaminophen use was slightly higher in the trained group ; however , the difference in pain relief remained statistically significant ( p = 0.0003 ) after adjustment for this difference . CONCLUSION This is the first study to demonstrate a positive effect of physician training on patients with a painful condition OBJECTIVE To examine whether telling symptomatic patients that they will soon be better shortens the duration of their illness . STUDY DESIGN AND SETTING We repeated an earlier trial in general practice on this subject . All our patients were reassured that they probably had no serious underlying disease . We r and omized 128 patients into two groups . Half of them got a clear diagnosis and were told that they would soon be better . The others heard from their general practitioners ( GPs ) that they probably had no serious underlying disease but that the GP did not know exactly what was wrong ; these patients were advised to come back later if necessary . For 78 patients , study protocol was followed exactly . RESULT Our trial could not show an effect . The Kaplan-Meier curves of patients with a positive and negative consultation ran nearly parallel . The hazard ratio in the total group was 0.97 ( 95 % precision interval PI=0.69 - 1.41 ) and in the optimal subgroup 0.91 ( 95 % PI=0.57 - 1.46 ) . We still can not rule out a modest placebo effect . CONCLUSION Our finding contrasts with that of the earlier trial . We think that symptomatic patients mainly want to know that they do not have a serious problem . Often , they will miss the extra information that they get-- and then they certainly can not benefit from it In a prospect i ve , r and omized study , we have examined the effects of preoperative and preinduction positive suggestion on postoperative emetic sequelae . A total of 226 patients were allocated r and omly to receive either positive suggestions or no suggestions . Those patients in the positive suggestion group were told before operation and on induction of anaesthesia that postoperative emetic sequelae would be greatly reduced by the use of two antiemetic drugs . Control patients were simply asked to participate in a study of postoperative well being with no mention of nausea or vomiting . Nausea , vomiting or retching , and antiemetic administration were measured in the first 24 h after operation . Antiemetic administration in the positive suggestion group was 16.5 % less than in the control group ( P = 0.03 ) but there was no significant difference between the groups in nausea or vomiting-retching There is conflicting evidence on the efficacy of traditional Chinese acupuncture ( TCA ) , and the role of placebo effects elicited by acupuncturists ' behavior has not been eluci date d. We conducted a 3‐month r and omized clinical trial in patients with knee osteoarthritis to compare the efficacy of TCA with sham acupuncture and to examine the effects of acupuncturists ' communication styles PURPOSE The aim of this study was to identify the effects of a communication skills training ( CST ) program for oncologists , developed based on patient preferences regarding oncologists ' communication . PARTICIPANTS AND METHODS Thirty oncologists were r and omly assigned to either an intervention group ( IG ; 2-day CST workshop ) or control group ( CG ) . Participants were assessed on their communication performance during simulated consultation and their confidence in communicating with patients at baseline and follow-up . A total of 1,192 patients ( response rate , 84.6 % ) who had consultations with the participating oncologists at baseline and /or follow-up were assessed regarding their distress using the Hospital Anxiety and Depression Scale , satisfaction with the consultation , and trust in their oncologist after the consultation . RESULTS At the follow-up survey , the performance scores of the IG had improved significantly , in terms of their emotional support ( P = .011 ) , setting up a supportive environment ( P = .002 ) , and ability to deliver information ( P = .001 ) , compared with those of the CG . Oncologists in the IG were rated higher at follow-up than those in the CG in terms of their confidence in themselves ( P = .001 ) . Patients who met with oncologists after they had undergone the CST were significantly less depressed than those who met with oncologists in the CG ( P = .027 ) . However , the CST program did not affect patient satisfaction with oncologists ' style of communication . CONCLUSION A CST program based on patient preferences is effective for both oncologists and patients with cancer . Oncologists should consider CST as an approach to enhancing their communication skills BACKGROUND Information that enhances expectations about drug effectiveness improves the response to placebos for pain . Although asthma symptoms often improve with placebo , it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit . OBJECTIVE The study objective was to determine whether response to placebo or a leukotriene antagonist ( montelukast ) can be augmented by messages that increase expectation of benefit . METHODS A r and omized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups . Participants were r and omly assigned to one of 4 treatment groups in a factorial design ( ie , placebo with enhanced messages , placebo with neutral messages , montelukast with enhanced messages , or montelukast with neutral messages ) or to usual care . Assignment to study drug was double masked , assignment to message content was single masked , and usual care was not masked . The enhanced message aim ed to increase expectation of benefit from the drug . The primary outcome was mean change in daily peak flow over 4 weeks . Secondary outcomes included lung function and asthma symptom control . RESULTS Peak flow and other lung function measures were not improved in participants assigned to the enhanced message groups versus the neutral messages groups for either montelukast or placebo ; no differences were noted between the neutral placebo and usual care groups . Placebo-treated participants had improved asthma control with the enhanced message but not montelukast-treated participants ; the neutral placebo group did have improved asthma control compared with the usual care group after adjusting for baseline difference . Headaches were more common in participants provided messages that mentioned headache as a montelukast side effect . CONCLUSIONS Optimistic drug presentation augments the placebo effect for patient-reported outcomes ( asthma control ) but not lung function . However , the effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness BACKGROUND Continuous care ( one anaesthesiologist per patient ) and anaesthesiologist empathy at the preoperative visit could affect patient anxiety and satisfaction . We tested both unproven issues in a population at increased risk of anxiety and dissatisfaction . METHODS In this single-blinded single-centre study , 136 women undergoing gynaecologic day-care surgery were sequentially r and omized into four groups : ( i ) preoperative visit by an anaesthesiologist with either an empathic or a neutral attitude , and ( ii ) receiving either continuous or divided care ( preoperative visit and anaesthesia performed by two different anaesthesiologists ) . Preoperative anxiety and wish for information were rated before and after the preoperative visit . Patient appraisal of the anaesthesiologist 's attitude and the quality of care provided was obtained in the operating theatre . RESULTS An empathic attitude at the preoperative visit significantly improved the perception of both the anaesthesiologist attitude ( P<0.001 ) and the quality of information delivered ( P<0.001 ) , compared with a neutral anaesthesiologist attitude . Empathic attitude tended to decrease patient anxiety . In the operating theatre , patients who had the same anaesthesiologist ( continuous care ) exhibited greater satisfaction levels regarding anaesthesiologist behaviour and quality of care ( P<0.001 ) . Principal component analysis confirmed these findings , revealing that an empathic preoperative visit was linked to a reduction in preoperative patient anxiety . CONCLUSIONS The ' one patient , one anaesthesiologist ' model , in addition to ensuring sufficient time for open discussion and questions at the preoperative visit , improved patient satisfaction |
2,356 | 28,940,130 | Conclusion In summary , this meta- analysis shows that vitrification at any stage has no detrimental effect on clinical outcome .
Blastocyst transfer will still remain a favorable and promising option in ART . | Objective This systematic review sought to evaluate the clinical outcomes of vitrification at the cleavage stage and blastocyst stage for embryo transfer in patients undergoing assisted reproductive technology ( ART ) treatment . | Surplus embryos available for cryopreservation in fresh cycles are considered as having good potential for future use . However , the optimal stage of embryo cryopreservation remains unclear . In this study , 1190 patients with surplus embryos on day 3 were divided into two groups : cleavage-stage embryo cryopreservation ( control group ) and blastocyst cryopreservation ( blastocyst group ) . The clinical outcomes of the subsequent warming cycles were evaluated . The proportion of cycles with blastocyst formation was 73.8 % in the blastocyst group . Although in the blastocyst group , the cancellation rate of blastocyst transfer was increased due to lack of blastocysts available for cryopreservation , the blastocyst group achieved significantly higher rates of clinical pregnancy/cycle ( 43.2 % versus 34.9 % ; P=0.003 ) , pregnancy/transfer ( 59.5 % versus 35.4 % ; P<0.001 ) and implantation ( 46.5 % versus 22.2 % ; P<0.001 ) from the first warming cycle compared with the control group . In an embryo-number classified analysis , the clinical pregnancy rate was also higher in the blastocyst group . However , the cumulative pregnancy was similar between the two groups . Blastocyst culture as an embryo selection tool will not improve embryo viability but it will help patients to achieve pregnancy more quickly . Extended culture of surplus embryos to the blastocyst stage for cryopreservation optimizes the clinical outcomes Objective It is well known that fresh blastocyst transfer results in better pregnancy outcomes with a smaller number of transferred embryos compared with cleavage stage embryo transfer . However , in terms of frozen-thawed blastocyst transfer , only a few studies are available . We aim ed to evaluate clinical outcomes of frozen-thawed embryo transfer ( FET ) with blastocysts . Methods Retrospective analysis of FET cycles with blastocysts ( B-FET ) between Jan 2007 and June 2009 was performed . Age-matched FET cycles with cleavage stage embryos ( C-FET ) during the same period were collected as controls . A total of 58 B-FET cycles were compared with 172 C-FET cycles and also compared with those of post-thaw extended culture blastocysts from frozen pronuclear stage embryos ( 22 cycles ) . Results There was no difference in the patient characteristics of each group . The embryos ' survival rates after thawing were comparable ( > 90 % ) and there was no difference in the implantation rate or clinical and ongoing pregnancy rate among the three groups . Conclusion In FET , blastocyst transfers may not present better pregnancy outcomes than cleavage stage embryo transfers . A further large-scale prospect i ve study is needed Conventionally , most in vitro fertilization ( IVF ) embryos are transferred in fresh treatment cycles with freezing reserved for spare ones . Improvement in cryopreservation facilities over time has encouraged the greater use of this technology with the success rate of frozen replacement cycles approaching that associated with fresh embryo transfer . Data from observational studies suggest that obstetric and perinatal outcomes are better in pregnancies result ing from frozen replacement cycles . In the interests of promoting feto-maternal safety is it therefore time to avoid fresh embryo transfers in IVF , freeze all available embryos and replace them in subsequent cycles ? In this article we explore the biological plausibility of this concept , appraise the evidence underpinning it and consider the implication s of adopting such a strategy in routine clinical practice . The outcomes of existing r and omized trials appear to favour a strategy of frozen embryo transfer , but larger trials are needed before a major change in clinical practice can be considered High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF-embryo transfer outcome . This prompted us to quantify prospect ively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation , up to the time of blastocyst transfers , in 43 IVF-embryo transfer c and i date s. Contractility was assessed on the day of human chorionic gonadotrophin ( HCG ) administration , 4 days after HCG ( non-cavitating embryo transfer ; HCG + 4 ) , and 7 days after HCG ( blastocyst transfers ; HCG + 7 ) . For this , 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency . Our results indicated that a slight , yet significant , decrease in uterine contraction frequency , observed from the day of HCG ( 4.4 + /- 0.2 contractions/min ) to HCG + 4 ( 3.5 + 0.2 contractions/min ) , was followed by a more pronounced , additional decrease between HCG + 4 and HCG + 7 ( 1.5 + /- 0.2 contractions/min ; P < 0.001 ) . In conclusion , during the luteal phase of ovarian stimulation , uterine contractility decreases progressively , and reaches a nearly quiescent status 7 days after HCG administration , at the time of blastocyst transfers . It is possible that such a uterine relaxation assists blastocyst implantation BACKGROUND Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age . We design ed a prospect i ve , r and omized , controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage ( day 3 ) embryo and those undergoing transfer of a single blastocyst-stage ( day 5 ) embryo . METHODS We studied 351 infertile women under 36 years of age who were r and omly assigned to undergo transfer of either a single cleavage-stage embryo ( 176 patients ) or a single blastocyst-stage embryo ( 175 patients ) . Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone . RESULTS The study was terminated early after a prespecified interim analysis ( which included 50 percent of the planned number of patients ) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo ( P=0.02 ) . The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo ( 32.0 percent vs. 21.6 percent ; relative risk , 1.48 ; 95 percent confidence interval , 1.04 to 2.11 ) . Two multiple births occurred , both of monozygotic twins , both of which were in the group undergoing transfer of a single cleavage-stage embryo . CONCLUSIONS These findings support the transfer of a single blastocyst-stage ( day 5 ) embryo in infertile women under 36 years of age Purpose To determine if blastocyst transfer increases the ongoing and cumulative pregnancy rates , compared with day 3 embryo transfer , in women of all ages when at least 4 zygotes are obtained . Methods Prospect i ve study including patients undergoing a first IVF/ICSI treatment and assigned to cleavage stage ( n = 46 ) or blastocyst ( n = 58 ) embryo transfer . Supernumerary embryos were vitrified and patients failing to achieve an ongoing pregnancy after fresh embryo transfer would go through cryopreserved cycles . The main outcome measure was the ongoing pregnancy rate after the fresh IVF/ICSI transfer and the cumulative ongoing pregnancy rate . Results were also analyzed according to age ( under 35 and 35 or older ) . Results A majority of patients ( 96.6 % ) had a blastocyst transfer when at least 4 zygotes were obtained . The ongoing pregnancy rate was significantly higher in the day-5 group compared with the day-3 group ( 43.1 % vs. 24 % , p = 0.041 ) . The cumulative ongoing pregnancy rate was higher ( but not significantly ) with blastocyst than with cleavage stage embryos ( 56.8 % vs. 43.4 % , p = 0.174 ) . When analysed by age , patients 35 or older showed significantly higher ongoing pregnancy rate ( 48.4 % vs. 19.3 % , p = 0.016 ) and cumulative ongoing pregnancy rate ( 58 % vs. 25.8 % , p = 0.01 ) in the day-5 group compared to the day-3 group , while no such differences were observed in women under 35 . Conclusions Blastocyst transfer can be suggested whenever there are at least 4 zygotes . While there are no differences in women under 35 , the benefit of this option over cleavage stage transfer could be significant in women 35 or older OBJECTIVE To compare the implantation and pregnancy rates after cleavage stage embryo transfer ( ET ) with transfer of blastocyst-stage ( days 5 - 6 ) embryos . STUDY DESIGN Prospect i ve r and omized trial at an assisted reproduction unit in a university hospital . Women with six or more follicles at the last ultrasound scan before oocyte aspiration were r and omized for transfer of a maximum of two embryos after 2 - 3 days ( n = 80 ) or after 5 - 6 days ( n = 64 ) of culture . Embryo quality , implantation and pregnancy rates were evaluated . Statistical significance was tested with the Chi-square test and Fisher 's exact test . RESULT ( S ) No significant difference was observed in implantation rates ( 21.1 % versus 20.9 % , respectively ) and clinical pregnancy rates ( 36.7 % versus 32.5 % respectively ) after blastocyst and cleavage stage transfers for the two groups . The pregnancy rate among subjects who had at least one good quality embryo transferred was 37.5 % per day 2 - 3 ET and 60 % per day 5 - 6 ET . CONCLUSION ( S ) The overall implantation and pregnancy rates after embryo transfer at cleavage stage and at blastocyst stage transfer were not statistically different . Women who had at least one good quality blastocyst ( n = 25 ) had a high pregnancy rate ( 60 % per ET ) . Blastocyst transfer is a good alternative for couples with many good quality embryos on day 2 after insemination |
2,357 | 25,440,385 | These studies showed significant effectiveness in one or more outcomes for mental health and behavior .
Although there was insufficient evidence in the studies of HT due to poor method ological and reporting quality and heterogeneity , HT may be an effective treatment for mental and behavioral disorders such as dementia , schizophrenia , depression , and terminal-care for cancer | AIM To summarize the evidence from r and omized controlled trials ( RCTs ) on the effects of horticultural therapy ( HT ) . | BACKGROUND The conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments BACKGROUND Clear , transparent , and sufficiently detailed abstract s of conferences and journal articles related to r and omized controlled trials ( RCTs ) are important , because readers often base their assessment of a trial solely on information in the abstract . Here , we extend the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement to develop a minimum list of essential items , which authors should consider when reporting the results of a RCT in any journal or conference abstract . METHODS AND FINDINGS We generated a list of items from existing quality assessment tools and empirical evidence . A three-round , modified-Delphi process was used to select items . In all , 109 participants were invited to participate in an electronic survey ; the response rate was 61 % . Survey results were presented at a meeting of the CONSORT Group in Montebello , Canada , January 2007 , involving 26 participants , including clinical trialists , statisticians , epidemiologists , and biomedical editors . Checklist items were discussed for eligibility into the final checklist . The checklist was then revised to ensure that it reflected discussion s held during and subsequent to the meeting . CONSORT for Abstract s recommends that abstract s relating to RCTs have a structured format . Items should include details of trial objectives ; trial design ( e.g. , method of allocation , blinding/masking ) ; trial participants ( i.e. , description , numbers r and omized , and number analyzed ) ; interventions intended for each r and omized group and their impact on primary efficacy outcomes and harms ; trial conclusions ; trial registration name and number ; and source of funding . We recommend the checklist be used in conjunction with this explanatory document , which includes examples of good reporting , rationale , and evidence , when available , for the inclusion of each item . CONCLUSIONS CONSORT for Abstract s aims to improve reporting of abstract s of RCTs published in journal articles and conference proceedings . It will help authors of abstract s of these trials provide the detail and clarity needed by readers wishing to assess a trial 's validity and the applicability of its results Abstract Background . Cancer survivors are at increased risk for second malignancies , cardiovascular disease , diabetes , and functional decline . Evidence suggests that a healthful diet and physical activity may reduce the risk of chronic disease and improve health in this population . Methods . We conducted a feasibility study to evaluate a vegetable gardening intervention that paired 12 adult and child cancer survivors with Master Gardeners to explore effects on fruit and vegetable intake , physical activity , quality -of-life , and physical function . Throughout the year-long study period , the survivor-Master Gardener dyads worked together to plan/plant three gardens , harvest/rotate plantings , and troubleshoot/correct problems . Data on diet , physical activity , and quality -of-life were collected via surveys ; anthropometrics and physical function were objective ly measured . Acceptability of the intervention was assessed with a structured debriefing survey . Results . The gardening intervention was feasible ( robust enrollment ; minimal attrition ) and well-received by cancer survivors and Master Gardeners . Improvement in three of four objective measures of strength , agility , and endurance was observed in 90 % of survivors , with the following change scores [ median ( interquartile range ) ] noted between baseline and one-year follow-up : h and grip test [ + 4.8 ( 3.0 , 6.7 ) kg ] , 2.44 meter Get-Up- and -Go [ + 1.0 ( + 1.8 , + 0.2 ) seconds ] , 30-second chair st and [ + 3.0 ( + 1.0 , 5.0 ) st and s ] , and six-minute walk [ + 11.6 ( 6.1 , 48.8 ) meters ] . Increases of ≥ 1 fruit and vegetable serving/day and ≥ 30 minutes/week of physical activity were observed in 40 % and 60 % , respectively . Conclusion . These preliminary results support the feasibility and acceptability of a mentored gardening intervention and suggest that it may offer a novel and promising strategy to improve fruit and vegetable consumption , physical activity , and physical function in cancer survivors . A larger r and omized controlled trial is needed to confirm our results 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 PURPOSE To assess the effects of horticultural therapy ( HT ) on mood state and heart rate ( HR ) in patients participating in an inpatient cardiac rehabilitation program . METHODS Cardiac rehabilitation in patients ( n = 107 ) participated in the study . The HT group consisted of 59 subjects ( 34 males , 25 females ) . The control group , which participated in patient education classes ( PECs ) , consisted of 48 subjects ( 31 males , 17 females ) . Both HT sessions and PEC are components of the inpatient rehabilitation program . Each group was evaluated before and after a class in their respective modality . Evaluation consisted of the completion of a Profile of Mood States ( POMS ) inventory , and an HR obtained by pulse oximetry . RESULTS Changes in the POMS total mood disturbance ( TMD ) score and HR between preintervention and postintervention were compared between groups . There was no presession difference in either TMD score ( 16 + /- 3.6 and 19.0 + /- 3.2 , PEC and HT , respectively ) or HR ( 73.5 + /- 2.5 and 79 + /- 1.8 , PEC and HT , respectively ) . Immediately following the intervention , the HT TMD was significantly reduced ( post-TMD = 1.6 + /- 3.2 , P < .001 ) , while PEC TMD was not significantly changed ( TMD = 17.0 + /- 28.5 ) . After intervention , HR fell in HT by 4 + /- 9.6 bpm ( P < .001 ) but was unchanged in PEC . CONCLUSION These findings indicate that HT improves mood state , suggesting that it may be a useful tool in reducing stress . Therefore , to the extent that stress contributes to coronary heart disease , these findings support the role of HT as an effective component of cardiac rehabilitation CONTEXT Therapists can use horticultural therapy as an adjuvant therapy in a non threatening context , with the intent of bringing about positive effects in physical health , mental health , and social interaction . Very few experimental studies exist that test its clinical effectiveness . OBJECTIVE To determine whether the addition of horticultural therapy to a pain-management program improved physical function , mental health , and ability to cope with pain . DESIGN The research team design ed a prospect i ve , nonr and omized , controlled cohort study , enrolling all patients consecutively referred to the Zurzach Interdisciplinary Pain Program ( ZISP ) who met the study s criteria . The team divided them into two cohorts based on when medical professionals referred them : before ( control group ) or after ( intervention group ) introduction of a horticultural therapy program . SETTING The setting was the rehabilitation clinic ( RehaClinic ) in Bad Zurzach , Switzerl and . PARTICIPANTS Seventy-nine patients with chronic musculoskeletal pain ( fibromyalgia or chronic , nonspecific back pain ) participated in the study . INTERVENTIONS The research team compared a 4-week , inpatient , interdisciplinary pain-management program with horticultural therapy ( intervention , n = 37 ) with a pain-management program without horticultural therapy ( control , n = 42 ) . The horticultural therapy program consisted of seven sessions of group therapy , each of 1-hour duration . OUTCOME MEASURES The research team assessed the outcome using the Medical Outcome Study Short Form-36 ( SF-36 ) , the West Haven-Yale Multidimensional Pain Inventory ( MPI ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Coping Strategies Question naire ( CSQ ) , and two functional performance tests . The team tested participants on entry to and discharge from the 4-week pain-management program . RESULTS Between-group differences in sociodemographic and outcome variables were not significant on participants entry to the pain-management program . On discharge , the research team measured small to moderate outcome effects ( effect size [ ES ] up to 0.71 ) within both groups . The study found significantly larger improvements for the horticultural therapy group vs the control group in SF-36 role physical ( ES = 0.71 vs 0.22 ; P = .018 ) ; SF-36 mental health ( ES = 0.46 vs 0.16 ; P = .027 ) ; HADS anxiety ( ES = 0.26 vs 0.03 ; P = .043 ) ; and CSQ pain behavior ( ES = 0.30 vs -0.05 ; P = .032 ) . CONCLUSION The addition of horticultural therapy to a pain management program improved participants ' physical and mental health and their coping ability with respect to chronic musculoskeletal pain PURPOSE We examined the effects of communication skills training and the use of memory books by certified nursing assistants ( CNAs ) on verbal interactions between CNAs ( n = 64 ) and nursing home residents ( n = 67 ) during care routines . DESIGN AND METHODS CNAs were taught to use communication skills and memory books during their interactions with residents with moderate cognitive impairments and intact communication abilities . A staff motivational system was used to encourage performance and maintenance of these skills . Formal measures of treatment implementation were included . RESULTS Results were compared with those for participants on no-treatment control units . Trained CNAs talked more , used positive statements more frequently , and tended to increase the number of specific instructions given to residents . Changes in staff behavior did not result in an increase in total time giving care to residents . Maintenance of CNA behavior change was found 2 months after research staff exited the facility . Although an increase was found in positive verbal interactions between CNAs and residents on intervention units , other changes in resident communication were absent . IMPLICATION S Nursing staff can be trained to improve and maintain communication skills during care without increasing the amount of time delivering care . The method ological advantages of including measures to assess treatment implementation are discussed Objective To investigate the effect of the CONSORT for Abstract s guidelines , and different editorial policies used by five leading general medical journals to implement the guidelines , on the reporting quality of abstract s of r and omised trials . Design Interrupted time series analysis . Sample We r and omly selected up to 60 primary reports of r and omised trials per journal per year from five high impact , general medical journals in 2006 - 09 , if indexed in PubMed with an electronic abstract . We excluded reports that did not include an electronic abstract , and any secondary trial publications or economic analyses . We classified journals in three categories : those not mentioning the guidelines in their instructions to authors ( JAMA and New Engl and Journal of Medicine ) , those referring to the guidelines in their instructions to authors but with no specific policy to implement them ( BMJ ) , and those referring to the guidelines in their instructions to authors with an active policy to implement them ( Annals of Internal Medicine and Lancet ) . Two authors extracted data independently using the CONSORT for Abstract s checklist . Main outcome Mean number of CONSORT items reported in selected abstract s , among nine items reported in fewer than 50 % of the abstract s published across the five journals in 2006 . Results We assessed 955 reports of abstract s of r and omised trials . Journals with an active policy to enforce the guidelines showed an immediate increase in the level of mean number of items reported ( increase of 1.50 items ; P=0.0037 ) . At 23 months after publication of the guidelines , the mean number of items reported per abstract for the primary outcome was 5.41 of nine items , a 53 % increase compared with the expected level estimated on the basis of pre-intervention trends . The change in level or trend did not increase in journals with no policy to enforce the guidelines ( BMJ , JAMA , and New Engl and Journal of Medicine ) . Conclusion Active implementation of the CONSORT for Abstract s guidelines by journals can lead to improvements in the reporting of abstract s of r and omised trials Engaging persons with dementia in meaningful activities supports well-being ; however , care staff are challenged to implement age- and ability-appropriate activities in a group setting . We compared a r and omly assigned treatment group , who received horticultural therapy-based ( HT-based ) programming to a comparison group , who engaged in traditional activities ( TA ) programming , on engagement and affect . Horticultural therapy-based programming was implemented twice weekly at 4 treatment sites for 6 weeks , while regular TA were observed at comparison sites . Results revealed no differences between groups on affective domains . Levels of adaptive behavior differed between the groups , with the treatment group demonstrating higher levels of active , passive , and other engagement and the comparison group demonstrating higher levels of self-engagement . Our results highlight the value of HT-based programs and the importance of simultaneously capturing participants ’ affective and behavioral responses . Theoretical and practical considerations about the facilitation of and context in which the programming occurs are discussed Support for prospect i ve registration of protocol s for systematic review s has been gathering momentum . The PRISMA statement , a guideline for reporting systematic review s and meta-analyses of studies that evaluate health-care interventions , advocates registration . Well-conducted systematic review s are accepted as the best- quality evidence to inform policy and practice , and the dramatic upward trend in the number of systematic review s published annually ( fi gure ) is set to continue . However , there is currently no single facility for identifying this type of research in advance of the appearance of the results of the review . There is concern about and evidence of publication and selective outcome -reporting biases associated with systematic review s. An open registry of review s captured at the protocol stage would facilitate good practice in systematic review s by providing transparency of the review process and outcomes . Discrepancies between the methods of the published review and those planned in the registered protocol could be more readily identifi ed . Registration might also encourage full publication of the review ’s fi ndings and transparency in changes to methods that could bias fi ndings . In both the prevention and revelation of potential bias , registration should improve quality and increase confi dence that policy or practice informed by the fi ndings of systematic review s are indeed drawing on best- quality evidence . A registry of protocol s of systematic review s could assist those planning new review s and updating existing ones . Easy access to information about ongoing review s should help to optimise the use of fi nite re sources by enabling funding and commissioning agencies to avoid unnecessary duplication and encourage collaboration . A comprehensive registry could also create opportunities for method ological and other research , both within and across disciplines . Existing access to systematic - review protocol s is limited to the outputs of individual organisations , such as the Cochrane and Campbell Collaborations and the Joanna Briggs Institute . The National Public Health Service for Wales is piloting an All Wales Systematic Review s Register , but , up to now , there has been no central ised comprehensive registry of systematic - review protocol s. We are developing an international facility to register the details of ongoing systematic review s in health and social care . Our registry is being established with the existing platform and infrastructure that supports the Data base of Abstract s of Review s of Eff ects ( DARE ) , the NHS Economic Evaluations Data base ( NHS EED ) and the Health Technology Assessment ( HTA ) data base produced by the Centre for Review s and Dissemination . The initial scope of the registry will be limited to systematic review s of the eff ectiveness of health interventions . However , the longterm aim is for the registry to include details of all ongoing systematic review s with a health-related outcome in the broadest sense . Ultimately , inclusion will encompass systematic review s of health-care interventions , and review s of the social determinants of health , of service delivery , and of risk factors and genetic associations . Our web-based registry will off er free public access , be electronically search able , and open to all prospect i ve registrants . Registration will require the provision of a minimum data set , the completeness of which will be checked automatically before registration . After acceptance , the registry ’s entry and protocol for the review , if available , will be loaded on the data base as a permanent entry and a unique identifi cation number issued . An audit trail for any amendments to the information will be available within the record . Links to result ing publications will be added . These provisions ensure that the registry will match the relevant criteria required of clinical trials registries R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly |
2,358 | 23,868,190 | Benefit was reported for other cancer-related symptoms , including pain , fatigue , hot flushes , xerostomia , dyspnoea and anxiety .
Much of the primary research reported in review s is innovative and indicates potential benefit for people with cancer-related symptoms . | Purpose This study aims to systematic ally appraise the evidence for the use of acupuncture for symptom management in cancer and supportive care and to identify recommendations for clinical practice and future research . | OBJECTIVES To determine the effect of acupuncture on hot flash frequency and intensity , quality of life , and sleep quality in patients undergoing hormonal therapy for prostate cancer . Hot flashes are a common adverse effect of hormonal therapy for prostate cancer . METHODS Men who had a hot flash score > 4 who were receiving and rogen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks , then weekly for 6 weeks , using a predefined treatment plan . The primary endpoint was a 50 % reduction in the hot flash score after 4 weeks of therapy , calculated from the patients ' daily hot flash diaries . The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes , including serotonin , calcitonin gene-related peptide , and urinary 5-hydroxyindoleacetic acid , were examined . RESULTS A total of 25 men were enrolled from September 2003 to April 2007 . Of these , 22 were eligible and evaluable . After 4 weeks , 9 ( 41 % , 95 % confidence interval 21%-64 % ) of 22 patients had had a > 50 % reduction in the hot flash score . Of the 22 patients , 12 ( 55 % , 95 % confidence interval 32%-76 % ) met this response definition at any point during the therapy course . No patient had a significant increase in hot flash score during therapy . A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality . CONCLUSIONS Multiple placebo-controlled trials have demonstrated a 25 % response rate to placebo treatment for hot flashes . Of the 22 patients , 41 % had responded by week 4 and 55 % overall in the present pilot study , providing evidence of a potentially meaningful benefit . Additional studies of acupuncture for hot flashes in this population are warranted PURPOSE Most men who undergo castration therapy for prostatic carcinoma will have vasomotor symptoms that usually persist for years . Vasomotor symptoms are elicited from the thermoregulatory center , possibly due to a decrease in hypothalamic opioid activity induced by low sex steroid concentrations . Acupuncture treatment in women , which stimulates hypothalamic opioid activity , alleviates vasomotor symptoms . We report on men treated with acupuncture for relief of vasomotor symptoms after castration therapy . MATERIAL S AND METHODS We asked 7 men with vasomotor symptoms due to castration therapy to receive acupuncture treatment 30 minutes twice weekly for 2 weeks and once a week for 10 weeks . Effects on flushes were recorded in logbooks . RESULTS Of the 7 men 6 completed at least 10 weeks of acupuncture therapy and all had a substantial decrease in the number of hot flushes ( average 70 % after 10 weeks ) . At 3 months after the last treatment the number of flushes was 50 % lower than before therapy . Therapy was discontinued after 10 weeks because of a femoral neck fracture in 1 man and after 3 weeks due to severe back pain in 1 . CONCLUSIONS Acupuncture may be a therapeutic alternative in men with hot flushes after castration therapy and merits further evaluation Recommendations for treatment are commonly based on results evaluating variation in systematic effects ( group responses ) from r and omised controlled trials without taking the individual patient 's variation into account . In the evaluation of acupuncture-related treatment effects , the trial design and statistical analysis used are a challenge since the assessed variables commonly have subjective properties and are based on the person 's own self-report . Thus , the results that are seen are often varied , most likely due to inter-individual variation in rating of the actual variable such that the treatment effects are expressed more ( or less ) in some individuals than in others . The basis for the individual variation is probably multi-modal and could be related to the individuals ’ expectation , gender , genetic polymorphisms and the aetiology of the condition . The assessment methods used should preferably have proven useful in controlled trials , and the methods for statistical analysis should consider the non-metric properties of the variable and the contribution of the individuals ’ variation in the results . In order to evaluate the treatment effects more properly and increase the possibility of detecting any effectiveness , it is therefore important to assess the level of perceived dysfunction or symptom , taking into account the individual variation as well as the systematic effects ( the effects of the group ) . In the evaluation of acupuncture effects , both systematic and individual variation should be reported allowing for the detection of subgroup effects and thereby leading to treatment recommendations that are more likely to be based on each individual 's specific needs BACKGROUND Radiation treatment of head and neck cancer can cause chronic xerostomia which impairs patients ' quality of life . The study reported here examined the efficacy of acupuncture in alleviating xerostomia symptoms especially dry mouth . PATIENTS AND METHODS A total of 145 patients with chronic radiation-induced xerostomia > 18 months after treatments were recruited from seven UK cancer centres . The study employed a r and omised crossover design with participants receiving two group sessions of oral care education and eight of acupuncture using st and ardised methods . Patient-reported outcome ( PROs ) measures were completed at baseline and weeks 5 , 9 , 13 , 17 , and 21 . The primary outcome was improvement in dry mouth . OBJECTIVE saliva measurements were also carried out . RESULTS Acupuncture compared with oral care , produced significant reductions in patient reports of severe dry mouth ( OR = 2.01 , P = 0.031 ) sticky saliva ( OR = 1.67 , P = 0.048 ) , needing to sip fluids to swallow food ( OR = 2.08 , P = 0.011 ) and in waking up at night to drink ( OR = 1.71 , P = 0.013 ) . There were no significant changes in either stimulated or unstimulated saliva measurements over time . CONCLUSION Eight sessions of weekly group acupuncture compared with group oral care education provide significantly better relief of symptoms in patients suffering from chronic radiation-induced xerostomia More than 70 % of seriously ill patients with cancer suffer from xerostomia and the associated problems of swallowing , chewing and speaking . This study aims to investigate whether treatment with acupuncture is a viable option for hospice patients with xerostomia . During a 2-year period , 117 patients were assessed for xerostomia . Eighty-two patients were found to have moderate xerostomia . Sixty-seven fulfilled the criteria for inclusion . Of these , 14 were included but only eight completed the study . Ten acupuncture treatments were given during a 5-week period . The effect of acupuncture was measured using a visual analogue scale , and by measuring the saliva production before and after the series of treatment . The results show that all the patients experienced alleviation of dryness of the mouth and the associated symptoms , and thus benefited from the acupuncture treatment . However , conducting a 5-week acupuncture intervention study is not feasible at an inpatient hospice due to the patients being too close to death Purpose / Objective : Patients with cancer or symptoms referable to cancer therapy were offered acupuncture as potential palliation of their symptoms . This paper describes the physical integration of the discipline into the Oncology Clinic , and patient perspectives on its availability and efficacy . Patients and methods : Between August 1999 and May 2000 , 123 patients with varying symptoms received acupuncture in our Center 's Radiation and Medical Oncology Clinics and Breast Health Center . These patients had 823 visits during this time period . A practice outcome analysis was performed on patients receiving therapy between 1 January 2000 and 30 April 2000 . The 89 patients treated during this interval had 444 total visits . In June and July 2000 , a question naire was administered by phone to 79 of these patients ( 89 % ) . St and ard allopathic care continued while patients were receiving acupuncture . Results : Major reasons for referral included pain ( 53 % ) , xerostomia ( 32 % ) , hot flashes ( 6 % ) and nausea/loss of appetite ( 6 % ) . Patients had a mean of five acupuncture visits ( range 1– 9 ) . Most patients ( 60 % ) showed at least 30 % improvement in their symptoms . About one-third of patients had no change in severity of symptoms . There were no untoward effects reported related to the acupuncture . When analysed by diagnosis , these values persist . Irrespective of response to therapy , 86 % of respondents considered it ‘ very important ' that we continue to provide acupuncture services . Conclusion : Acupuncture may contribute to control of symptoms for cancer patients . Expansion of providers , continued patient follow-up , optimization of techniques and prospect i ve objective measurement of response continue in our clinic Of 21 patients with severe xerostomia , 11 were treated with acupuncture and 10 patients received placebo acupuncture . Those patients who received acupuncture treatment showed increased salivary flow rates during and after the acupuncture treatment . The improved salivary values persisted during the observation year , whereas the patients who received placebo acupuncture showed some improvement of salivary flow rates only during the actual treatment . The results of the present study indicate that acupuncture may be a useful adjunct for the stimulation of salivary flow in some patients with xerostomia PURPOSE We aim ed to assess the effectiveness of acupuncture for cancer-related fatigue ( CRF ) in patients with breast cancer . PATIENTS AND METHODS We conducted a pragmatic , r and omized controlled trial comparing acupuncture with enhanced usual care . Three hundred two out patients with breast cancer participated . We r and omly assigned 75 patients to usual care and 227 patients to acupuncture plus usual care ( r and om assignment of 1:3 respectively ) with minimization controlling for baseline general fatigue and maintenance treatment . Treatment was delivered by acupuncturists once a week for 6 weeks through needling three pairs of acupoints . The usual care group received a booklet with information about fatigue and its management . Primary outcome was general fatigue at 6 weeks , measured with the Multidimensional Fatigue Inventory ( MFI ) . Other measurements included the Hospital Anxiety and Depression Scale , Functional Assessment of Cancer Therapy-General quality -of-life scale , and expectation of acupuncture effect . Analyses were by intention to treat . RESULTS Two hundred forty-six of 302 patients r and omly assigned provided complete data at 6 weeks . The difference in the mean General Fatigue score , between those who received the intervention and those who did not , was -3.11 ( 95 % CI , -3.97 to -2.25 ; P < .001 ) . The intervention also improved all other fatigue aspects measured by MFI , including Physical Fatigue and Mental Fatigue ( acupuncture effect , -2.36 and -1.94 , respectively ; both at P < .001 ) , anxiety and depression ( acupuncture effect , -1.83 and -2.13 , respectively ; both at P < .001 ) , and quality of life ( Physical Well-Being effect , 3.30 ; Functional Well-Being effect , 3.57 ; both at P < .001 ; Emotional Well-Being effect , 1.93 ; P = .001 ; and Social Functioning Well-Being effect , 1.05 ; P < .05 ) . CONCLUSION Acupuncture is an effective intervention for managing the symptom of CRF and improving patients ' quality of life The m and ate of Human Reproduction Up date involves several roles : ( i ) to provide a synthesis of evidence that can aid scientists and clinicians in their daily work ; ( ii ) to help reproductive specialists underst and concepts from related disciplines ; and ( iii ) to summarize current knowledge generated by basic science as the foundation of future scientific and clinical advancement . Given that review and synthesis are central to good scientific and clinical practice , and that a grasp of the current state of knowledge is a prerequisite to design ing new studies , it is pertinent to ask which review s are most likely to fulfil the needs of readers . A related question concerns whether systematic review s meet the needs of all review topics and all readers . Summarizing evidence or knowledge is a difficult problem in reproductive medicine , as in other branches of science and medical care ( Eddy et al. , 1992 ) . For each question there may be multiple studies that use different design s and inclusion criteria . For clinical questions , the interventions , outcomes and measures of effect may vary : the effect measures in treatment studies include odds ratios , relative risks and absolute differences . For scientific questions , the experimental species , models and design s may differ . Moreover , it is always uncertain whether all of the relevant evidence has been evaluated . Even when the search has been exhaustive , there are no simple guides on how to interpret conflicting results and whether to accept apparently outlying studies . The choices that the review er makes to address the variable conditions and uncertainties may be conservative , strict and exclusive , or liberal , open and inclusive . The decisions made by the review er may not be consistent throughout and these choices may or may not satisfy the reader who seeks out the review to address a clinical or research question . Faced with uncertainty and doubt , readers nonetheless must form an impression of the evidence and synthesize the state of knowledge in order to address the clinical or research question that stimulated their interest in the review . We argue that the reader is better served when the choices made in the review , regardless of whether they are strict or open , should be explicit , transparent , clearly stated and reproducible by interested readers . This list of objectives for review s is more easily satisfied by systematic review s , which use explicit methods to method ically search , critically appraise and synthesize the available literature on a specific issue . The question or issue need not be clinical : indeed , the concept evolved primarily in psychology studies ( Light and Pillemer , 1984 ) . The systematic review attempts to reduce review er bias through the use of objective , reproducible criteria to select relevant individual publications and assess their validity . A systematic review may include a meta- analysis or statistical summary of the individual study results : the aggregate of effects from several studies yields an average treatment effect that is more precise than the individual study results ( Schlesselman and Collins , 2003 ) . Thus , the systematic review involves explicit , transparent methods which are clearly stated , and reproducible by others . Whether a systematic review of r and omized controlled trials adheres to the guidelines can easily be evaluated by means of a widely used checklist ( the QUORUM statement ) ( Moher et al. , 1999 ) . The strengths of the systematic review include the narrow focus of the question , the comprehensive search for evidence , the criterion-based selection of relevant evidence , the rigorous appraisal of validity , the objective or quantitative summary , and the evidence -based inferences ( Cook et al. , 1997 ) . For some review topics , however , the strengths of the systematic review may turn into weaknesses . The primary problem is that the narrow focus and prescribed methods of the systematic review do not allow for comprehensive coverage . For example , the historical review is an irreplaceable means of tracing the development of a scientific principle or clinical concept , but the narrative thread could be lost in the strict rules of systematic review . As other examples , it would be burdensome to apply systematic methods to a survey on aneuploidy and fertility in the aging female or to an assessment of mouse knockout models and polycystic ovarian phenotype . Such topics would require the wider scope of a traditional narrative review , in Human Reproduction Up date , Vol.11 , No.2 pp . 103–104 , 2005 doi:10.1093/humupd/dmh058 Advance Access publication December 23 , BACKGROUND Cancer-related fatigue after chemotherapy is a difficult symptom to manage in practice and the most disruptive symptom in patients ' lives . Acupuncture is a popular complementary therapy among cancer patients and some evidence exists that it could potentially alleviate fatigue by stimulating ' energy ' points in the body . Hence , this study was carried out to assess the effects of acupuncture and acupressure in managing cancer-related fatigue and the feasibility of running a r and omised trial with these two complementary therapies in preparation for a large trial . METHODS This study was a r and omised controlled trial . Forty-seven patients with cancer who experienced moderate to severe fatigue were r and omised either to an acupuncture group ( n=15 ) , an acupressure group ( n=16 ) or a sham acupressure group ( n=16 ) . The acupuncture group received six 20-min sessions over 2 weeks , while the patients in the two acupressure groups were taught to massage/press the points and did so daily thereafter for 2 weeks on their own . Patients completed the Multidimensional Fatigue Inventory before r and omisation , at the end of the 2-week intervention and again about 2 weeks after the end of the intervention . RESULTS Significant improvements were found with regards to General fatigue ( P<0.001 ) , Physical fatigue ( P=0.016 ) , Activity ( p=0.004 ) and Motivation ( P=0.024 ) . At the end of the intervention , there was a 36 % improvement in fatigue levels in the acupuncture group , while the acupressure group improved by 19 % and the sham acupressure by 0.6 % . Improvements were observed even 2 weeks after treatments , although they were lower ( 22 % , 15 % , 7 % , respectively ) . Acupuncture was a more effective method than acupressure or sham acupressure . Subjects needed a longer treatment period to have more sustained results . The trial was method ologically feasible . CONCLUSION Acupuncture shows great potential in the management of cancer-related fatigue . As a r and omised trial with acupuncture is feasible and preliminary data shows significant improvements , it should be tested further using a large sample and a multicentre design 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 Background . Acupuncture is underutilized as an adjunct cancer therapy . The main study objectives were to determine the feasibility of administering acupuncture as palliative therapy to patients with advanced ovarian or breast cancer and to assess the effect on symptoms and quality of life ( QOL ) . Methods . This study was a pilot , single-armed prospect i ve clinical trial for patients with advanced cancer to receive 12 acupuncture sessions over 8 weeks with follow-up at weeks 9 and 12 . Ambulatory patients with advanced ovarian or breast cancer were enrolled to receive treatments at an outpatient academic oncology center . Symptom severity was measured before and after each acupuncture session . A composite QOL assessment tool , consisting of vali date d instruments , was completed at 5 time points . Results . Forty patients enrolled in the study . Twenty-eight patients ( 70 % ; 95 % confidence interval [ CI ] = 53%-83 % ) completed 4 weeks of treatment , and 26 patients ( 65 % ; 95 % CI = 48%-79 % ) completed 8 weeks . Eight patients ( 20 % ) withdrew before receiving acupuncture , and 6 patients ( 15 % ) discontinued treatment early because of disease progression or scheduling dem and s. Among all 32 assessed patients , there was self-reported improvement immediately post-treatment in anxiety , fatigue , pain , and depression and significant improvement over time for patients with anxiety ( P = .001 ) and depression ( P = .02 ) . Among patients experiencing baseline symptoms , there was improvement in anxiety ( P = .001 ) , fatigue ( P = .0002 ) , pain ( P = .0002 ) , and depression ( P = .003 ) . QOL measures of pain severity and interference , physical and psychological distress , life satisfaction , and mood states showed improved scores during treatment , with sustained benefit at 12 weeks . Conclusions . This pilot study demonstrates that an 8-week outpatient acupuncture course is feasible for advanced cancer patients and produces a measurable benefit that should be evaluated in controlled trials BACKGROUND Hot flushes are common and distressing among men with castrational treatment for prostate cancer . Of the few treatments , most have side effects . OBJECTIVE Assess changes in hot flushes of electrostimulated ( EA ) and traditional acupuncture ( TA ) . DESIGN , SETTING , AND PARTICIPANTS Thirty-one men with hot flushes due to prostate cancer treatment were recruited from three urological departments in Sweden , from 2001 to 2004 . INTERVENTION Thirty-one men were r and omized to EA ( 12 needle points , with 4 electrostimulated ) or TA ( 12 needle points ) weekly for 12 wk . MEASUREMENTS PRIMARY OUTCOME number of and distress from hot flushes in 24 h and change in " hot flush score . " Secondary outcome : change in 24-h urine excretion of CGRP ( calcitonin gene-related peptide ) . RESULTS AND LIMITATIONS Twenty-nine men completed the treatment . Hot flushes per 24 h decreased significantly , from a median of 7.6 ( interquartile range [ IQR ] , 6.0 - 12.3 ) at baseline in the EA group to 4.1 ( IQR , 2.0 - 6.5 ) ( p=0.012 ) after 12 wk , and from 5.7 ( IQR , 5.1 - 9.5 ) in the TA group to 3.4 ( IQR1.8 - 6.3 ) ( p=0.001 ) . Distress by flushes decreased from 8.2 ( IQR , 6.5 - 10.7 ) in the EA group to 3.3 ( IQR , 0.3 - 8.1 ) ( p=0.003 ) , and from 7.6 ( IQR , 4.7 - 8.3 ) to 3.4 ( IQR , 2.0 - 5.6 ) ( p=0.001 ) in the TA group after 12 wk , ( 78 % and 73 % reduction in " hot flush score , " respectively ) . The effect lasted up to 9 mo after treatment ended . CGRP did not change significantly . Few , minor side effects were reported . LIMITATIONS small number of patients ; no placebo control , instead a small group controlled for 6 wk pretreatment . CONCLUSIONS EA and TA lowered number of and distress from hot flushes . The hot flush score decreased 78 % and 73 % , respectively , in line with or better than medical regimens for these symptoms . Acupuncture should be considered an alternative treatment for these symptoms , but further evaluation is needed , preferably with a non- or placebo-treated control group |
2,359 | 25,795,928 | RESULTS We found that interventions based only on advice had modest results in identifying changes in the anthropometric indicators of children and adolescents over time , although they appear to be effective in promoting positive changes in the eating habits of this population .
CONCLUSION Intervention programs based only on counseling are effective in promoting changes in dietary patterns , but show poor results in the changes of anthropometric parameters of children and adolescents | OBJECTIVE This study aims to conduct a literature review to evaluate the effectiveness of intervention programs in the prevention and control of obesity in children and to map the locations where the studies were carried out . | Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention Objective To evaluate the effectiveness of a school-based intervention involving the families and teachers that aim ed to promote healthy eating habits in adolescents ; the ultimate aim of the intervention was to reduce the increase in body mass index ( BMI ) of the students . Design Paired cluster r and omized school-based trial conducted with a sample of fifth grade rs . Setting Twenty classes were r and omly assigned into either an intervention group or a control group . Participants From a total of 574 eligible students , 559 students participated in the study ( intervention : 10 classes with 277 participants ; control : 10 classes with 282 participants ) . The mean age of students was 11 years . Intervention Students attended 9 nutritional education sessions during the 2010 academic year . Parents/guardians and teachers received information on the same subjects . Main Outcome Measurement Changes in BMI and percentage of body fat . Results Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups ( β = 0.003 ; p = 0.75 ) . There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group ; students in this group also consumed more fruits . Conclusion Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet , but this did not lead to a reduction in BMI gain . Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents . Trial Registration Clinical trials.gov NCT01046474 The purpose of this study was to assess the effects of a six-months ’ nutrition program , delivered and taught by classroom teachers with in-service nutrition training , on the prevention of overweight and obesity among children in grade s 1 to 4 . In this r and omized trial , four hundred and sixty four children from seven elementary schools were allocated to a nutrition educational program delivered by their own teachers . Intervened teachers had 12 sessions of three hours each with the research ers throughout six months , according to the topics nutrition and healthy eating , the importance of drinking water and healthy cooking activities . After each session , teachers were encouraged to develop activities in class focused on the learned topics . Sociodemographic , anthropometric , dietary , and physical activity assessment s were performed at baseline and at the end of the intervention . In the intervention group the increase in Body Mass Index ( BMI ) z-score was significantly lower than in the control group ( p = 0.009 ) ; fewer proportion of children became overweight in the intervened group compared with the control ( 5.6 % vs. 18.4 % ; p = 0.037 ) . Our study provides further support to decrease the overweight epidemic , involving classroom teachers in a training program and making them dedicated interventionists Objectives To assess the behavioural and weight status outcomes in English children in a feasibility study of a novel primary school-based obesity prevention programme . Design Exploratory cluster r and omised controlled trial of the Healthy Lifestyles Programme . Setting Four city primary schools ( two control and two intervention ) in the South West of Engl and . Participants 202 children aged 9–10 years , of whom 193 and 188 were followed up at 18 and 24 months , respectively . No child was excluded from the study ; however , to be eligible , schools were required to have at least one single Year 5 class . Intervention Four-phase multicomponent programme using a range of school-based activities including lessons , assemblies , parents ' evenings , interactive drama workshops and goal setting to engage and support schools , children and their families in healthy lifestyle behaviours . It runs over the spring and summer term of Year 5 and the autumn term of Year 6 . Primary and secondary outcomes Weight status outcomes were body mass index , waist circumference and body fat st and ard deviation scores ( SDS ) at 18 and 24 months , and behavioural outcomes were physical activity , television ( TV ) viewing/screen time and food intake at 18 months . Results At 18 months of follow-up , intervention children consumed less energy-dense snacks and more healthy snacks ; had less ‘ negative food markers ’ , more ‘ positive food markers ’ , lower mean TV/screen time and spent more time doing moderate-vigorous physical activity each day than those in the control schools . Intervention children had lower anthropometric measures at 18 and 24 months than control children , with larger differences at 24 months than at 18 months for nearly all measures . Conclusions Results from this exploratory trial show consistent positive changes in favour of the intervention across all targeted behaviours , which , in turn , appear to affect weight status and body shape . A definitive trial is now justified OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices Objectives To examine the prospect i ve associations between body mass index ( BMI ) , waist circumference , and fat mass in childhood and cardiovascular risk factors at age 15 - 16 . Design Prospect i ve cohort study . Setting Avon Longitudinal Study of Parents and Children . Participants 5235 children aged 9 - 12 at start of study . Main exposures BMI , waist circumference , and fat mass determined by dual energy x ray absorptiometry , assessed at age 9 - 12 and at age 15 - 16 . Main outcome measures Systolic and diastolic blood pressure and concentrations of fasting glucose , insulin , triglycerides , low density lipoprotein cholesterol , and high density lipoprotein cholesterol assessed at age 15 - 16 . Results In girls a 1 SD greater BMI at age 9 - 12 was associated with cardiovascular risk factors at age 15 - 16 in fully adjusted models : odds ratio 1.23 ( 95 % confidence interval 1.10 to 1.38 ) for high systolic blood pressure ( ≥130 mm Hg ) ; 1.19 ( 1.03 to 1.38 ) for high concentration of low density lipoprotein cholesterol ( ≥2.79 mmol/l ) ; 1.43 ( 1.06 to 1.92 ) for high concentration of triglycerides ( ≥1.7 mmol/l ) ; 1.25 ( 1.08 to 1.46 ) for low concentration of high density lipoprotein cholesterol ( < 1.03 mmol/l ) ; and 1.45 ( 1.22 to 1.73 ) for high concentration of insulin ( ≥16.95 IU/l ) . Equivalent results in boys were 1.24 ( 1.13 to 1.37 ) for systolic blood pressure ; 1.30 ( 1.07 to 1.59 ) for low density lipoprotein cholesterol ; 1.96 ( 1.51 to 2.55 ) for triglycerides ; 1.39 ( 1.22 to 1.57 ) for high density lipoprotein cholesterol , and 1.84 ( 1.56 to 2.17 ) for insulin . BMI was associated with high fasting glucose ( ≥5.6 mmol/l ) only in boys ( 1.18 , 1.03 to 1.36 ) . With these binary outcomes there was statistical evidence that associations differed between girls and boys for fasting glucose ( P=0.03 ) and insulin ( P<0.001 ) . When risk factors were examined as continuous outcomes there was evidence for stronger associations of BMI with more adverse levels in boys than girls for fasting insulin , glucose , and triglyceride concentrations ( all interaction P≤0.03 ) . BMI , waist circumference , and fat mass were all strongly correlated with each other ( r=0.89 - 0.94 ) , and associations of the three with cardiovascular outcomes were of similar magnitude with statistical evidence of consistency in associations ( all P>0.2 for heterogeneity ) . When waist circumference or fat mass or both were added to models including BMI they did not increase the variation in cardiovascular risk factors already explained by BMI and confounders alone . Girls who were overweight/obese at age 9 - 12 but were normal weight by 15 - 16 had similar odds of adverse levels of risk factors to those who were normal weight at both ages . In boys odds of high systolic blood pressure , high concentrations of triglycerides and insulin , and low concentrations of high density lipoprotein cholesterol remained higher in this group compared with those who were normal weight at both ages but were lower than in those who remained overweight/obese at both ages . Conclusions Measurements of waist circumference or directly assessed fat mass in childhood do not seem to be associated with cardiovascular risk factors in adolescence any more strongly than BMI . Girls who favourably alter their overweight status between childhood and adolescence have cardiovascular risk profiles broadly similar to those who were normal weight at both time points , but boys who change from overweight to normal show risk factor profiles intermediate between those seen in boys who are normal weight at both ages or overweight at both ages OBJECTIVES : The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program ( Challenge ! ) on changes in BMI status , body composition , physical activity , and diet . METHODS : A total of 235 black adolescents ( aged 11–16 years ; 38 % overweight/obese ) were recruited from low-income urban communities . Baseline measures included weight , height , body composition , physical activity ( PA ) , and diet . PA was measured by 7-day play-equivalent physical activity ( ≥1800 activity counts per minute ) . Participants were r and omly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control . Postintervention ( 11 months ) and delayed follow-up ( 24 months ) evaluations were conducted . Longitudinal analyses used multilevel models with r and om intercepts and generalized estimating equations , controlling for baseline age/gender . Stratified analyses examined baseline BMI category . RESULTS : Retention was 76 % over 2 years ; overweight/obese status declined 5 % among intervention adolescents and increased 11 % among control adolescents . Among overweight/obese youth , the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up . Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations . CONCLUSIONS : At postintervention , there were intervention effects on diet and PA but not BMI category or body composition . At delayed follow-up , dietary changes were sustained and the intervention prevented an increase in BMI category . Body composition was improved for overweight/obese youth . Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention BACKGROUND This study evaluated a school-based obesity intervention for elementary school children ( N = 835 ) where health professionals assisted teachers with the integration of healthy messages into the school curriculum . METHODS Schools were r and omized into a professional-facilitated intervention ( PFI ; N = 4 ) or a self-help ( SH ; N = 3 ) condition . Changes in weight-based outcomes were assessed in students enrolled in the second grade from all 7 schools ( overall : N = 835 students ; PFI : N = 509 students , SH : N = 326 students ) . Students were between ages 7 and 9 and from diverse ethnic background s ( Asian = 25.3 % , Black = 23.3 % , Hispanic = 23.1 % , White = 28.3 % ) . The sample included 321 overweight/obese ( BMI ≥ 85th percentile ) , 477 normal-weight ( BMI ≥ 5th percentile and < 85th percentile ) , and 37 underweight ( BMI < 5th percentile ) students . RESULTS After 2 years , children who were overweight/obese in the PFI condition significantly reduced their st and ardized BMI ( z BMI ) compared to children in the SH condition ( Wald χ(2 ) = 28.7 , p < .001 ) . End-of-year grade s decreased for overweight/obese students in both conditions ; however , students in the PFI exhibited a smaller decrease in grade s compared to the SH condition ( Wald χ(2 ) = 80.3 , p < .001 ) . CONCLUSION The results indicate that an obesity prevention program where health professionals assist teachers by integrating healthy messages into existing curriculum was effective in reducing z BMI compared to the SH condition |
2,360 | 25,547,090 | Overall , these studies found only modest improvements in some of the recommended clinician actions on tobacco use .
AUTHORS ' CONCLUSIONS Documentation of tobacco status and referral to cessation counselling appears to increase following EHR modifications design ed to prompt the recording and treating of tobacco use at healthcare visits . | BACKGROUND Health information systems such as electronic health records ( EHR ) , computerized decision support systems , and electronic prescribing are potentially valuable components to improve the quality and efficiency of clinical interventions for tobacco use .
OBJECTIVES To assess the effectiveness of electronic health record-facilitated interventions on smoking cessation support actions by clinicians , clinics , and healthcare delivery systems and on patient smoking cessation outcomes . | BACKGROUND Because smoking has a profound impact on socioeconomic disparities in illness and death , it is crucial that vulnerable population s of smokers be targeted with treatment . The U.S. Public Health Service recommends that all patients be asked about their smoking at every visit and that smokers be given brief advice to quit and referred to treatment . PURPOSE Initiatives to facilitate these practice s include the 5A 's ( ask , advise , assess , assist , arrange ) and Ask-Advise-Refer ( AAR ) . Unfortunately , primary care referrals are low , and most smokers referred fail to enroll . This study evaluated the efficacy of the Ask-Advise-Connect ( AAC ) approach to linking smokers with treatment in a large , safety net public healthcare system . DESIGN The study design was a pair-matched group-r and omized trial with two treatment arms . SETTING / PARTICIPANTS Ten safety net clinics in Houston TX . INTERVENTION Clinics were r and omized to AAC ( n=5 ; intervention ) or AAR ( n=5 ; control ) . Licensed vocational nurses ( LVNs ) were trained to assess and record the smoking status of all patients at all visits in the electronic health record . Smokers were given brief advice to quit . In AAC , the names and phone numbers of smokers who agreed to be connected were sent electronically to the Texas quitline daily , and patients were proactively called by the quitline within 48 hours . In AAR , smokers were offered a quitline referral card and encouraged to call on their own . Data were collected between June 2010 and March 2012 and analyzed in 2012 . MAIN OUTCOME MEASURES The primary outcome was impact , defined here as the proportion of identified smokers that enrolled in treatment . RESULTS The impact ( proportion of identified smokers who enrolled in treatment ) of AAC ( 14.7 % ) was significantly greater than the impact of AAR ( 0.5 % ) , t(4)=14.61 , p=0.0001 , OR=32.10 ( 95 % CI=16.60 , 62.06 ) . CONCLUSIONS The AAC approach to aiding smoking cessation has tremendous potential to reduce tobacco-related health disparities Background To determine the effectiveness of a single checklist reminder form to improve the delivery of preventive health services at adult health check-ups in a family practice setting . Methods A prospect i ve cluster r and omized controlled trial was conducted at four urban family practice clinics among 38 primary care physicians affiliated with the University of Toronto . Preventive Care Checklist Forms © were created to be used by family physicians at adult health check-ups over a five-month period . The sex-specific forms incorporate evidence -based recommendations on preventive health services and documentation space for routine procedures such as physical examination . The forms were used in two intervention clinics and two control clinics . Rates and relative risks ( RR ) of the performance of 13 preventive health maneuvers at baseline and post-intervention and the percentage of up-to- date preventive health services delivered per patient were compared between the two groups . Results R and omly-selected charts were review ed at baseline ( n = 509 ) and post-intervention ( n = 608 ) . Baseline rates for provision of preventive health services ranged from 3 % ( fecal occult blood testing ) to 93 % ( blood pressure measurement ) , similar to other setting s. The percentage of up-to- date preventive health services delivered per patient at the end of the intervention was 48.9 % in the control group and 71.7 % in the intervention group . This is an overall 22.8 % absolute increase ( p = 0.0001 ) , and 46.6 % relative increase in the delivery of preventive health services per patient in the intervention group compared to controls . Eight of thirteen preventive health services showed a statistically significant change ( p < 0.05 ) in favor of the intervention ( adjusted RR ( 95 % C.I. ) ) : counseling on brushing/flossing teeth ( 9.2 ( 4.3–19.6 ) ) , folic acid counseling ( 7.5 ( 2.7–20.8 ) ) , fecal occult blood testing ( 6.7 ( 1.9–24.1 ) ) , smoking cessation counseling ( 3.9 ( 2.2–7.2 ) ) , tetanus immunization ( 3.0 ( 1.7–5.2 ) ) , history of alcohol intake ( 1.33 ( 1.2–1.5 ) ) , history of smoking habits ( 1.28 ( 1.2–1.4 ) ) and blood pressure measurement ( 1.05 ( 1.00–1.10 ) ) . Conclusion This simple , low cost , clinical ly relevant intervention improves the delivery of preventive health services by prompting physicians of evidence -based recommendations in a checklist format that incorporates existing practice patterns . Periodic up date s of the Preventive Care Checklist Forms © will allow a feasible and easy-to-use tool for primary care physicians to provide evidence -based preventive health services to adults at routine health check-ups . The forms can also be incorporated into an electronic health record . The Preventive Care Checklist Forms © are accessible in English and French at the College of Family Physicians of Canada web site OBJECTIVE To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation . STUDY DESIGN A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care . METHODS The study was performed at 18 Veterans Health Administration ( VA ) sites in California . Participants were VA patients receiving primary care . We r and omly allocated 10 of 18 sites to receive the Telephone Care Coordination Program , which included simple 2-click referral , proactive care coordination , medication management , and 5 follow-up telephone calls . Each patient received a 30- to 45-minute counseling session from the California Smokers ' Helpline . Patients at control sites received usual care . RESULTS During 10 months , we received 2965 referrals . We were unable to reach 1156 patients ( 39 % ) , despite at least 3 attempts . We excluded 73 patients ( 3 % ) , and 391 patients ( 13 % ) were not interested . We connected the remaining 1345 patients ( 45 % ) to the Helpline . At 6-month followup , 335 patients ( 11 % of all referrals and 25 % of participating patients ) were abstinent . Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites ( 15.6 vs 0.7 in the prior month ) . CONCLUSIONS The program generated a large number of referrals ; almost half of the patients referred were connected with the Helpline . Long-term abstinence was excellent . These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination Background : Strategies to improve smoking cessation counseling in clinical setting s are critical to supporting smokers ’ attempts to quit . This study evaluates the impact of adding 2 smoking-related vital sign questions in an electronic medical records system on identification , assessment , and counseling for patients who smoke : “ Current smoker ? ” and “ Plan to quit ? ” Methods : Baseline data and data after intervention were collected through record review of 899 r and omly selected patient visits across 3 outpatient clinics . Results : From before to after intervention , identification of smokers increased 18 % ( from 71 % to 84 % ; P < .001 ) , and assessment for a plan to quit increased 100 % ( from 25.5 % to 51 % ; P < .005 ) . Among all smokers , cessation counseling increased 26 % ( from 23.6 % to 29.8 % ; P = .41 ) . Significantly more smokers who received the assessment for a plan to quit received cessation counseling ( 46 % vs. 14 % , P < .001 ) . Regression analysis showed that patients receiving an assessment for plan to quit were 80 % more likely to receive cessation counseling ( OR 0.209 ; 95 % CI , 0.095–0.456 ) . Conclusions : Physician-documented counseling rates are significantly higher when patients are asked about smoking and assessed for a plan to quit . Two questions that ask about smoking status and assess plans to quit may provide prompts to increase the likelihood that patients who smoke receive cessation counseling OBJECTIVE To evaluate the impact of a locally adapted evidence -based quality improvement ( EBQI ) approach to implementation of smoking cessation guidelines into routine practice . DATA SOURCES / STUDY SETTING We used patient question naires , practice surveys , and administrative data in Veterans Health Administration ( VA ) primary care practice s across five southwestern states . STUDY DESIGN In a group-r and omized trial of 18 VA facilities , matched on size and academic affiliation , we evaluated intervention practice s ' abilities to implement evidence -based smoking cessation care following structured evidence review , local priority setting , quality improvement plan development , practice facilitation , expert feedback , and monitoring . Control practice s received mailed guidelines and VA audit-feedback reports as usual care . DATA COLLECTION To represent the population of primary care-based smokers , we r and omly sample d and screened 36,445 patients to identify and enroll eligible smokers at baseline ( n=1,941 ) and follow-up at 12 months ( n=1,080 ) . We used computer-assisted telephone interviewing to collect smoking behavior , nicotine dependence , readiness to change , health status , and patient sociodemographics . We used practice surveys to measure structure and process changes , and administrative data to assess population utilization patterns . PRINCIPAL FINDINGS Intervention practice s adopted multifaceted EBQI plans , but had difficulty implementing them , ultimately focusing on smoking cessation clinic referral strategies . While attendance rates increased ( p<.0001 ) , we found no intervention effect on smoking cessation . CONCLUSIONS EBQI stimulated practice s to increase smoking cessation clinic referrals and try other less evidence -based interventions that did not translate into improved quit rates at a population level Cluster r and omized trials are increasingly common in general practice ( family medicine ) . This paper will consider the design and analysis of such trials and emphasize the similarities and differences with trials in education , heath promotion and public health . Issues discussed are the estimation and range of values of the intra-cluster correlation coefficient found in general practice , and the associated sample size problems . There are problems with widely varying numbers of subjects per cluster , which leads to planning and analysis difficulties . Ethical issues in these trials , and considerations such as the principle of intention to treat are also considered . An example of the type of analysis available for a continuous outcome variable is given , and the available software is summarized briefly IMPORTANCE Several national health care-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence -based treatments , such as quitline ( telephone-based tobacco cessation services ) assistance . The most notable examples are the 5 As ( Ask , Advise , Assess , Assist , Arrange ) and Ask . Advise . Refer . ( AAR ) programs . Unfortunately , rates of primary care referrals to quitlines are low , and most referred smokers fail to call for assistance . OBJECTIVE To evaluate a new approach -- Ask-Advise-Connect (AAC)-- design ed to address barriers to linking smokers with treatment . DESIGN A pair-matched , 2-treatment-arm , group-r and omized design in 10 family practice clinics in a single metropolitan area . Five clinics were r and omized to the AAC ( intervention ) and 5 to the AAR ( control ) conditions . In both conditions , clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record , and smokers were given brief advice to quit . In the AAC clinics , the names and telephone numbers of smokers who agreed to be connected were sent electronically to the quitline daily , and patients were called proactively by the quitline within 48 hours . In the AAR clinics , smokers were offered a quitline referral card and encouraged to call on their own . All data were collected from February 8 through December 27 , 2011 . SETTING Ten clinics in Houston , Texas . PARTICIPANTS Smoking status assessment s were completed for 42,277 patients ; 2052 unique smokers were identified at AAC clinics , and 1611 smokers were identified at AAR clinics . INTERVENTIONS Linking smokers with quitline-delivered treatment . MAIN OUTCOME MEASURE Impact was based on the RE- AIM ( Reach , Efficacy , Adoption , Implementation , and Maintenance ) conceptual framework and defined as the proportion of all identified smokers who enrolled in treatment . RESULTS In the AAC clinics , 7.8 % of all identified smokers enrolled in treatment vs 0.6 % in the AAR clinics ( t4 = 9.19 [ P < .001 ] ; odds ratio , 11.60 [ 95 % CI , 5.53 - 24.32 ] ) , a 13-fold increase in the proportion of smokers enrolling in treatment . CONCLUSIONS AND RELEVANCE The system changes implemented in the AAC approach could be adopted broadly by other health care systems and have tremendous potential to reduce tobacco-related morbidity and mortality BACKGROUND Preventive care is an important role for general practitioners , yet opportunities for prevention are often missed . METHOD We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice . All patients who attended were r and omised by the terminal digit of their record number . RESULTS The control uptake of opportunistic prevention was low ; ranging from 1.5 % ( tetanus immunisation ) to 27 % ( influenza immunisation ) . The reminders increased this by significant but small amounts for four out of 12 activities ( immunisation for tetanus and pneumococcus and recording of allergies and weight ) , insignificant increases for four ( mumps , measles and rubella immunisation , recording of smoking , and taking of cervical smears and of blood pressure ) , and insignificantly decreased influenza immunisation , and screening for diabetes and hyperlipidaemia . DISCUSSION Opportunistic electronic reminders have the potential to increase preventive care in general practice BACKGROUND To improve the documentation and treatment of tobacco use in primary care , we developed and implemented a 3-part electronic health record enhancement : (1)smoking status icons , ( 2 ) tobacco treatment reminders , and ( 3 ) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals . METHODS We performed a cluster-r and omized controlled trial of the enhancement in 26 primary care practice s between December 19 , 2006 , and September 30 , 2007 . The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor . Secondary outcomes included coded smoking status documentation and medication prescribing . RESULTS During the 9-month study period , 132 630 patients made 315 962 visits to study practice s. Coded documentation of smoking status increased from 37 % of patients to 54 % ( + 17 % ) in intervention practice s and from 35 % of patients to 46 % ( + 11 % ) in control practice s ( P < .001 for the difference in differences ) . Among the 9589 patients who were documented smokers at the start of the study , more patients in the intervention practice s were recorded as nonsmokers by the end of the study ( 5.3 % vs 1.9 % in control practice s ; P < .001 ) . Among 12 207 documented smokers , more patients in the intervention practice s made contact with a cessation counselor ( 3.9 % vs 0.3 % in control practice s ; P < .001 ) . Smokers in the intervention practice s were no more likely to be prescribed smoking cessation medication ( 2 % vs 2 % in control practice s ; P = .40 ) . CONCLUSION This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication BACKGROUND Decreases in smoking prevalence from recent decades have slowed , and national goals to reduce tobacco use remain unmet . Healthcare providers , including those in physician and dental teams , have access to evidence -based guidelines to help patients quit smoking . Translation of those guidelines into practice , however , remains low . Approaches that involve screening for drug use , brief intervention , and referral to treatment ( SBIRT ) are a promising , practical solution . PURPOSE This study examined whether dentists and dental hygienists would assess interest in quitting , deliver a brief tobacco intervention , and refer to a tobacco quitline more frequently as reported by patients if given computer-assisted guidance in an electronic patient record versus a control group providing usual care . DESIGN A blocked , group-r and omized trial was conducted from November 2010 to April 2011 . R and omization was conducted at the clinic level . Patients nested within clinics represented the lowest-level unit of observation . SETTING / PARTICIPANTS Participants were patients in HealthPartners dental clinics . INTERVENTION Intervention clinics were given a computer-assisted tool that suggested scripts for patient discussion s. Usual care clinics provided care without the tool . MAIN OUTCOME MEASURES Primary outcomes were post-appointment patient reports of the provider assessing interest in quitting , delivering a brief intervention , and referring them to a quitline . RESULTS Patient telephone surveys ( 72 % response rate ) indicated that providers assessed interest in quitting ( control 70 % vs intervention 87 % , p=0.0006 ) ; discussed specific strategies for quitting ( control 26 % vs intervention 47 % , p=0.003 ) ; and referred the patient to a tobacco quitline ( control 17 % vs intervention 37 % , p=0.007 ) more frequently with the support of a computer-assisted tool integrated into the electronic health record . CONCLUSIONS Clinical decision support embedded in electronic health records can effectively help providers deliver tobacco interventions . These results build on evidence in medical setting s supporting this approach to improve provider-delivered tobacco cessation . TRIAL REGISTRATION This study is registered at Clinical Trials.govNCT01584882 The electronic health record ( EHR ) may be an effective tool to help clinicians address tobacco use more consistently . To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline , we conducted a cluster r and omized clinical trial ( feedback versus no feedback ) within 19 primary care clinics in Oregon . Intervention clinics received provider-specific monthly feedback reports generated from EHR data . The reports rated provider performance in asking , advising , assessing , and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care . During 12 months of follow-up , EHR-documented rates of advising , assessing , and assisting were significantly improved in the intervention clinics compared with the control clinics ( p<.001 ) . A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline . EHR-generated provider feedback improved documentation of assistance with tobacco cessation . Connecting physician offices to a state-level quitline was feasible and well accepted Editor 's Note : In order to encourage dissemination of the STROBE Statement , this article is being published simultaneously in Annals of Internal Medicine , Epidemiology , and PLoS Medicine . It is freely accessible on the Annals of Internal Medicine Web site ( www.annals.org ) and will also be published on the Web sites of Epidemiology and PLoS Medicine . The authors jointly hold the copyright of this article . For details on further use , see the STROBE Web site ( www.strobe-statement.org ) . Rational health care practice s require knowledge about the etiology and pathogenesis , diagnosis , prognosis , and treatment of diseases . R and omized trials provide valuable evidence about treatments and other interventions . However , much of clinical or public health knowledge comes from observational research ( 1 ) . About 9 of 10 research papers published in clinical specialty journals describe observational research ( 2 , 3 ) . The STROBE Statement Reporting of observational research is often not detailed and clear enough to assess the strengths and weaknesses of the investigation ( 4 , 5 ) . To improve the reporting of observational research , we developed a checklist of items that should be addressed : the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement ( Appendix Table ) . Items relate to the title , abstract , introduction , methods , results , and discussion sections of articles . The STROBE Statement has recently been published in several journals ( 6 ) . Our aim is to ensure clear presentation of what was planned , done , and found in an observational study . We stress that the recommendations are not prescriptions for setting up or conducting studies , nor do they dictate methodology or m and ate a uniform presentation . Appendix Table . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement : Checklist of Items That Should Be Addressed in Reports of Observational Studies STROBE provides general reporting recommendations for descriptive observational studies and studies that investigate associations between exposures and health outcomes . STROBE addresses the 3 main types of observational studies : cohort , casecontrol , and cross-sectional studies . Authors use diverse terminology to describe these study design s. For instance , follow-up study and longitudinal study are used as synonyms for cohort study , and prevalence study as a synonym for cross-sectional study . We chose the present terminology because it is in common use . Unfortunately , terminology is often used incorrectly ( 7 ) or imprecisely ( 8) . In Box 1 , we describe the hallmarks of the 3 study design s. Box 1 . Main Study Design s Covered by STROBE The Scope of Observational Research Observational studies serve a wide range of purpose s , from reporting a first hint of a potential cause of a disease to verifying the magnitude of previously reported associations . Ideas for studies may arise from clinical observations or from biological insight . Ideas may also arise from informal looks at data that lead to further explorations . Like a clinician who has seen thous and s of patients and notes 1 that strikes her attention , the research er may note something special in the data . Adjusting for multiple looks at the data may not be possible or desirable ( 9 ) , but further studies to confirm or refute initial observations are often needed ( 10 ) . Existing data may be used to examine new ideas about potential causal factors , and may be sufficient for rejection or confirmation . In other instances , studies follow that are specifically design ed to overcome potential problems with previous reports . The latter studies will gather new data and will be planned for that purpose , in contrast to analyses of existing data . This leads to diverse viewpoints , for example , on the merits of looking at subgroups or the importance of a predetermined sample size . STROBE tries to accommo date these diverse uses of observational research from discovery to refutation or confirmation . Where necessary , we will indicate in what circumstances specific recommendations apply . How to Use this Paper This paper is linked to the shorter STROBE paper that introduced the items of the checklist in several journals ( 6 ) , and forms an integral part of the STROBE Statement . Our intention is to explain how to report research well , not how research should be done . We offer a detailed explanation for each checklist item . Each explanation is preceded by an example of what we consider transparent reporting . This does not mean that the study from which the example was taken was uniformly well reported or well done ; nor does it mean that its findings were reliable , in the sense that they were later confirmed by others : It only means that this particular item was well reported in that study . In addition to explanations and examples , we included boxes with supplementary information . These are intended for readers who want to refresh their memories about some theoretical points or be quickly informed about technical background details . A full underst and ing of these points may require study ing the textbooks or method ological papers that are cited . STROBE recommendations do not specifically address topics , such as genetic linkage studies , infectious disease modeling , or case reports and case series ( 11 , 12 ) . As many of the key elements in STROBE apply to these design s , authors who report such studies may nevertheless find our recommendations useful . For authors of observational studies that specifically address diagnostic tests , tumor markers , and genetic associations , STARD ( 13 ) , REMARK ( 14 ) , and STREGA ( 15 ) recommendations may be particularly useful . The Items in the STROBE Checklist We now discuss and explain the 22 items in the STROBE checklist ( Appendix Table ) and give published examples for each item . Some examples have been edited by removing citations or spelling out abbreviations . Eighteen items apply to all 3 study design s , whereas 4 are design -specific . Starred items ( for example , item 8) indicate that the information should be given separately for cases and controls in casecontrol studies , or exposed and unexposed groups in cohort and cross-sectional studies . We advise authors to address all items somewhere in their paper , but we do not prescribe a precise location or order . For instance , we discuss the reporting of results under a number of separate items , while recognizing that authors might address several items within a single section of text or in a table . Title and Abstract 1(a ) Indicate the study 's design with a commonly used term in the title or the abstract . Example Leukaemia incidence among workers in the shoe and boot manufacturing industry : a casecontrol study ( 18 ) . Explanation Readers should be able to easily identify the design that was used from the title or abstract . An explicit , commonly used term for the study design also helps ensure correct indexing of articles in electronic data bases ( 19 , 20 ) . 1(b ) Provide in the abstract an informative and balanced summary of what was done and what was found . Example Background : The expected survival of HIV-infected patients is of major public health interest . Objective : To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population . Design : Population -based cohort study . Setting : All HIV-infected persons receiving care in Denmark from 1995 to 2005 . Patients : Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex , date of birth , and municipality of residence . Measurements : The authors computed KaplanMeier life tables with age as the time scale to estimate survival from age 25 years . Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient 's HIV diagnosis until death , emigration , or 1 May 2005 . Results : 3990 HIV-infected patients and 379 872 persons from the general population were included in the study , yielding 22 744 ( median , 5.8 y/person ) and 2 689 287 ( median , 8.4 y/person ) person-years of observation . Three percent of participants were lost to follow-up . From age 25 years , the median survival was 19.9 years ( 95 % CI , 18.5 to 21.3 ) among patients with HIV infection and 51.1 years ( CI , 50.9 to 51.5 ) among the general population . For HIV-infected patients , survival increased to 32.5 years ( CI , 29.4 to 34.7 ) during the 2000 to 2005 period . In the subgroup that excluded persons with known hepatitis C coinfection ( 16 % ) , median survival was 38.9 years ( CI , 35.4 to 40.1 ) during this same period . The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age , whereas the excess mortality rate increased with increasing age . Limitations : The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years . Conclusions : The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era . However , an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population ( 21 ) . Explanation The abstract provides key information that enables readers to underst and a study and decide whether to read the article . Typical components include a statement of the research question , a short description of methods and results , and a conclusion ( 22 ) . Abstract s should summarize key details of studies and should only present information that is provided in the article . We advise presenting key results in a numerical form that includes numbers of participants , estimates of associations , and appropriate measures of variability and uncertainty ( for example , odds ratios with confidence intervals ) . We regard it insufficient to state only that an exposure is or is not significantly associated with an BACKGROUND Conventional wisdom holds that older , busier clinicians who see complex patients are less likely to adopt and use novel electronic health record ( EHR ) functionality . METHODS To compare the characteristics of clinicians who did and did not use novel EHR functionality , we conducted a retrospective analysis of the intervention arm of a r and omized trial of new EHR-based tobacco treatment functionality . RESULTS The novel functionality was used by 103 of 207 ( 50 % ) clinicians . Staff physicians were more likely than trainees to use the functionality ( 64 % vs 37 % ; p<0.001 ) . Clinicians who graduated more than 10 years previously were more likely to use the functionality than those who graduated less than 10 years previously ( 64 % vs 42 % ; p<0.01 ) . Clinicians with higher patient volumes were more likely to use the functionality ( lowest quartile of number of patient visits , 25 % ; 2nd quartile , 38 % ; 3rd quartile , 65 % ; highest quartile , 71 % ; p<0.001 ) . Clinicians who saw patients with more documented problems were more likely to use the functionality ( lowest tertile of documented patient problems , 38 % ; 2nd tertile , 58 % ; highest tertile , 54 % ; p=0.04 ) . In multivariable modeling , independent predictors of use were the number of patient visits ( OR 1.2 per 100 additional patients ; 95 % CI 1.1 to 1.4 ) and number of documented problems ( OR 2.9 per average additional problem ; 95 % CI 1.4 to 6.1 ) . CONCLUSIONS Contrary to conventional wisdom , clinical ly busier physicians seeing patients with more documented problems were more likely to use novel EHR functionality |
2,361 | 20,633,738 | RESULTS The PHQ-9 and its abbreviated eight-item ( PHQ-8 ) and two-item ( PHQ-2 ) versions have good sensitivity and specificity for detecting depressive disorders .
Likewise , the GAD-7 and its abbreviated two-item ( GAD-2 ) version have good operating characteristics for detecting generalized anxiety , panic , social anxiety and post-traumatic stress disorder .
The optimal cutpoint is > or = 10 on the parent scales ( PHQ-9 and GAD-7 ) and > or = 3 on the ultra-brief versions ( PHQ-2 and GAD-2 ) .
The PHQ-15 is equal or superior to other brief measures for assessing somatic symptoms and screening for somatoform disorders .
Cutpoints of 5 , 10 and 15 represent mild , moderate and severe symptom levels on all three scales .
Sensitivity to change is well-established for the PHQ-9 and emerging albeit not yet definitive for the GAD-7 and PHQ-15 .
CONCLUSIONS The PHQ-9 , GAD-7 and PHQ-15 are brief well-vali date d measures for detecting and monitoring depression , anxiety and somatization | BACKGROUND Depression , anxiety and somatization are the most common mental disorders in primary care as well as medical specialty population s ; each is present in at least 5 - 10 % of patients and frequently comorbid with one another .
An efficient means for measuring and monitoring all three conditions would be desirable . | Abstract OBJECTIVE : There is a well-documented gap between diabetes care guidelines and the services received by patients in almost all health care setting s. This project reports initial results from a computer-assisted , patient-centered intervention to improve the level of recommended services received by patients from a wide variety of primary care providers . DESIGN AND SETTING S : Eight hundred eighty-six patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program . Physicians were stratified and r and omized to intervention or control conditions and evaluated on 2 primary outcomes : number of recommended laboratory screenings and recommended patient-centered care activities completed . Secondary outcomes were evaluated using the Problem Areas in Diabetes scale and the Patient Health Question naire (PHQ)-9 depression scale , and the RE- AIM framework was used to evaluate potential for dissemination . RESULTS : The program was well-implemented and significantly improved both number of recommended laboratory assays ( 3.4 vs 3.1 ; P<.001 ) and patient-centered aspects of diabetes care patients received ( 3.6 vs 3.2 ; P<.001 ) compared to those in r and omized control practice s. Activities that were increased most were foot exams ( follow-up rates of 80 % vs 52 % ; P<.003 ) and nutrition counseling ( 76 % vs 52 % ; P<.001 ) . CONCLUSIONS : Patients are very willing to participate in a brief computer-assisted intervention that is effective in enhancing quality of diabetes care . Staff in primary care offices can consistently deliver an intervention of this nature , but most physicians were unwilling to participate in this translation research study Background Evidence -based practice s design ed for large urban clinics are not necessarily portable into smaller isolated clinics . Implementing practice -based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists . Objective The purpose of the Telemedicine Enhanced Antidepressant Management ( TEAM ) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists . Design Matched sites were r and omized to the intervention or usual care . Participants Small VA Community-based outpatient clinics with no on-site psychiatrists , but access to telepsychiatrists . In 2003–2004 , 395 primary care patients with PHQ9 depression severity scores ≥12 were enrolled , and followed for 12 months . Patients with serious mental illness and current substance dependence were excluded . Measures Medication adherence , treatment response , remission , health status , health-related quality of life , and treatment satisfaction . Results The sample comprised mostly elderly , white , males with substantial physical and behavioral health comorbidity . At baseline , subjects had moderate depression severity ( Hopkins Symptom Checklist , SCL-20 = 1.8 ) , 3.7 prior depression episodes , and 67 % had received prior depression treatment . Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 ( odds ratio [ OR ] = 2.1 , p = .04 ) and 12 months ( OR = 2.7 , p = .01 ) . Intervention patients were more likely to respond by 6 months ( OR = 2.0 , p = .02 ) , and remit by 12 months ( OR = 2.4 , p = .02 ) . Intervention patients reported larger gains in mental health status and health-related quality of life , and reported higher satisfaction . Conclusions Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies BACKGROUND The eight-item Patient Health Question naire depression scale ( PHQ-8 ) is established as a valid diagnostic and severity measure for depressive disorders in large clinical studies . Our objectives were to assess the PHQ-8 as a depression measure in a large , epidemiological population -based study , and to determine the comparability of depression as defined by the PHQ-8 diagnostic algorithm vs. a PHQ-8 cutpoint > or = 10 . METHODS R and om-digit-dialed telephone survey of 198,678 participants in the 2006 Behavioral Risk Factor Surveillance Survey ( BRFSS ) , a population -based survey in the United States . Current depression as defined by either the DSM-IV based diagnostic algorithm ( i.e. , major depressive or other depressive disorder ) of the PHQ-8 or a PHQ-8 score > or = 10 ; respondent sociodemographic characteristics ; number of days of impairment in the past 30 days in multiple domains of health-related quality of life ( HRQoL ) . RESULTS The prevalence of current depression was similar whether defined by the diagnostic algorithm or a PHQ-8 score > or = 10 ( 9.1 % vs. 8.6 % ) . Depressed patients had substantially more days of impairment across multiple domains of HRQoL , and the impairment was nearly identical in depressed groups defined by either method . Of the 17,040 respondents with a PHQ-8 score > or = 10 , major depressive disorder was present in 49.7 % , other depressive disorder in 23.9 % , depressed mood or anhedonia in another 22.8 % , and no evidence of depressive disorder or depressive symptoms in only 3.5 % . LIMITATIONS The PHQ-8 diagnostic algorithm rather than an independent structured psychiatric interview was used as the criterion st and ard . CONCLUSIONS The PHQ-8 is a useful depression measure for population -based studies , and either its diagnostic algorithm or a cutpoint > or = 10 can be used for defining current depression CONTEXT Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease , but the mechanisms responsible for this association are unknown . OBJECTIVE To determine why depressive symptoms are associated with an increased risk of cardiovascular events . DESIGN AND PARTICIPANTS The Heart and Soul Study is a prospect i ve cohort study of 1017 out patients with stable coronary heart disease followed up for a mean ( SD ) of 4.8 ( 1.4 ) years . SETTING Participants were recruited between September 11 , 2000 , and December 20 , 2002 , from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12 , 2008 . MAIN OUTCOME MEASURES Baseline depressive symptoms were assessed using the Patient Health Question naire ( PHQ ) . We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events ( heart failure , myocardial infa rct ion , stroke , transient ischemic attack , or death ) was explained by baseline disease severity and potential biological or behavioral mediators . RESULTS A total of 341 cardiovascular events occurred during 4876 person-years of follow-up . The age-adjusted annual rate of cardiovascular events was 10.0 % among the 199 participants with depressive symptoms ( PHQ score > or = 10 ) and 6.7 % among the 818 participants without depressive symptoms ( hazard ratio [ HR ] , 1.50 ; 95 % confidence interval , [ CI ] , 1.16 - 1.95 ; P = .002 ) . After adjustment for comorbid conditions and disease severity , depressive symptoms were associated with a 31 % higher rate of cardiovascular events ( HR , 1.31 ; 95 % CI , 1.00 - 1.71 ; P = .04 ) . Additional adjustment for potential biological mediators attenuated this association ( HR , 1.24 ; 95 % CI , 0.94 - 1.63 ; P = .12 ) . After further adjustment for potential behavioral mediators , including physical inactivity , there was no significant association ( HR , 1.05 ; 95 % CI , 0.79 - 1.40 ; P = .75 ) . CONCLUSION In this sample of out patients with coronary heart disease , the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors , particularly physical inactivity CONTEXT Chronic pain is common in primary care patients and is associated with distress , disability , and increased health care use . OBJECTIVE To assess whether a collaborative intervention can improve chronic pain-related outcomes , including comorbid depression severity , in a Department of Veterans Affairs primary care setting . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized controlled trial of a collaborative care assistance with pain treatment intervention vs treatment as usual at 5 primary care clinics of 1 Department of Veterans Affairs Medical Center . Forty-two primary care clinicians were r and omized to the assistance with pain treatment intervention group or the treatment as usual group . The 401 patients had musculoskeletal pain diagnoses , moderate or greater pain intensity , and disability lasting 12 weeks or longer and were assigned to the same treatment groups as their clinicians . Recruitment occurred from January 2006 to January 2007 and follow-up concluded in January 2008 . INTERVENTION Assistance with pain treatment included a 2-session clinician education program , patient assessment , education and activation , symptom monitoring , feedback and recommendations to clinicians , and facilitation of specialty care . MAIN OUTCOME MEASURES Changes over 12 months in pain-related disability ( Rol and -Morris Disability Question naire , range of 0 - 24 ) , pain intensity ( Chronic Pain Grade [ CPG ] Pain Intensity subscale , range of 0 - 100 ) , and depression ( Patient Health Question naire 9 [ PHQ-9 ] , range of 0 - 27 ) , measured as beta coefficients ( difference in slopes in points per month ) . RESULTS Intervention patients had a mean ( SD ) of 10.6 ( 4.5 ) contacts with the assistance with pain treatment team . Compared with the patients receiving treatment as usual , intervention patients showed greater improvements in pain-related disability ( Rol and -Morris Disability Question naire beta , -0.101 [ 95 % confidence interval { CI } , -0.163 to -0.040 ] ; P = .004 and CPG Pain Intensity subscale beta , -0.270 [ 95 % CI , -0.480 to -0.061 ] ; P = .01 ) . Among patients with baseline depression ( PHQ-9 score > or = 10 ) , there was greater improvement in depression severity in patients receiving the intervention compared with patients receiving treatment as usual ( PHQ-9 beta , -0.177 [ 95 % CI , -0.295 to -0.060 ] ; P = .003 ) . The differences in scores between baseline and 12 months for the assistance with pain treatment intervention group and the treatment as usual group , respectively , were -1.4 vs -0.2 for the Rol and -Morris Disability Question naire , -4.7 vs -0.6 for the CPG Pain Intensity subscale , and -3.7 vs -1.2 for PHQ-9 . CONCLUSION The assistance with pain treatment collaborative intervention result ed in modest but statistically significant improvement in a variety of outcome measures . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00129480 OBJECTIVE To evaluate the psychometric properties of a single-item depression screen against vali date d scoring algorithms for the Patient Health Question naire ( PHQ ) and the utility of these algorithms in screening for depression and suicidality in a Department of Veterans Affairs ( VA ) primary care setting . STUDY DESIGN Recruitment phase of a r and omized trial . METHODS A total of 1211 Portl and VA patients with upcoming primary care clinic appointments were administered by telephone a single item assessing depressed mood over the past year and the PHQ . The PHQ-9 ( 9 items ) encompasses DSM-IV criteria for major depression , the PHQ-8 ( 8 items ) excludes the thoughts of death or suicide item , and the PHQ-2 ( 2 items ) assesses depressed mood and anhedonia . Patients whose responses suggested potential suicidality were administered 2 additional items assessing suicidal ideation . Patients receiving mental health specialty care were excluded . RESULTS Using the PHQ-9 algorithm for major depression as the reference st and ard , the VA single-item screen was specific ( 88 % ) but less sensitive ( 78 % ) . A PHQ-2 score of > or =3 demonstrated similar specificity ( 91 % ) with high sensitivity ( 97 % ) . For case finding , the PHQ-8 was similar to the PHQ-9 . Approximately 20 % of patients screened positive for moderate depression , 7 % reported thoughts of death or suicide , 2 % reported thoughts of harming themselves , and 1 % had specific plans . CONCLUSIONS The PHQ-2 offers brevity and better psychometric properties for depression screening than the single-item screen . The PHQ-9 item assessing thoughts of death or suicide does not improve depression case finding ; however , one third of patients endorsing this item reported recent active suicidal ideation PURPOSE Patients seeking care for medically unexplained physical symptoms pose a major challenge at primary care sites , and there are very few well-accepted and properly evaluated interventions to manage such patients . METHODS We tested the effectiveness of a cognitive behavior therapy (CBT)-type intervention delivered in primary care for patients with medically unexplained physical symptoms . Patients were r and omly assigned to receive either the intervention plus a consultation letter or usual clinical care plus a consultation letter . Physical and psychiatric symptoms were assessed at baseline , at the end of treatment , and at a 6-month follow-up . All treatments and assessment s took place at the same primary care clinic where patients sought care . RESULTS A significantly greater proportion of patients in the intervention group had physical symptoms rated by clinicians as “ very much improved ” or “ much improved ” compared with those in the usual care group ( 60 % vs 25.8 % ; odds ratio = 4.1 ; 95 % confidence interval , 1.9–8.8 ; P<.001 ) . The intervention ’s effect on unexplained physical symptoms was greatest at treatment completion , led to relief of symptoms in more than one-half of the patients , and persisted months after the intervention , although its effectiveness gradually diminished . The intervention also led to significant improvements in patient-reported levels of physical symptoms , patient-rated severity of physical symptoms , and clinician-rated depression , but these effects were no longer noticeable at follow-up . CONCLUSIONS This time-limited , CBT-type intervention significantly ameliorated unexplained physical complaints of patients seen in primary care and offers an alternative for managing these common and problematic complaints in primary care setting CONTEXT Most older adults with dementia will be cared for by primary care physicians , but the primary care practice environment presents important challenges to providing quality care . OBJECTIVE To test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were r and omized by physician to receive collaborative care management ( n = 84 ) or augmented usual care ( n = 69 ) at primary care practice s within 2 US university-affiliated health care systems from January 2002 through August 2004 . Eligible patients ( identified via screening or medical record ) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver . INTERVENTION Intervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient 's family caregiver and integrated within primary care . The team used st and ard protocol s to initiate treatment and identify , monitor , and treat behavioral and psychological symptoms of dementia , stressing nonpharmacological management . MAIN OUTCOME MEASURES Neuropsychiatric Inventory ( NPI ) administered at baseline and at 6 , 12 , and 18 months . Secondary outcomes included the Cornell Scale for Depression in Dementia ( CSDD ) , cognition , activities of daily living , re source use , and caregiver 's depression severity . RESULTS Initiated by caregivers ' reports , 89 % of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocol s. Intervention patients were more likely to receive cholinesterase inhibitors ( 79.8 % vs 55.1 % ; P = .002 ) and antidepressants ( 45.2 % vs 27.5 % ; P = .03 ) . Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months ( mean difference , -5.6 ; P = .01 ) and at 18 months ( mean difference , -5.4 ; P = .01 ) . Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months ; at 18 months , caregivers showed improvement in depression as measured by the Patient Health Question naire-9 . No group differences were found on the CSDD , cognition , activities of daily living , or on rates of hospitalization , nursing home placement , or death . CONCLUSIONS Collaborative care for the treatment of Alzheimer disease result ed in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers . These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00246896 Background and Purpose — Poststroke depression is a prevalent and disabling disorder , yet evidence regarding the effectiveness of treating poststroke depression is inconclusive . Our objective was to determine the effectiveness of the Activate-Initiate-Monitor care management program for the treatment of poststroke depression . Methods — We conducted a prospect i ve , r and omized , outcome -blinded trial in 188 ischemic stroke survivors identified at the time of admission to one of 4 Indianapolis hospitals . Depression screening and enrollment occurred between 1 and 2 months poststroke . The Activate-Initiate-Monitor intervention was a care management program that included Activation of the patient to recognize depression symptoms and accept treatment , Initiation of an antidepressant medication , and Monitoring and adjusting treatment . Usual care subjects received nondepression-related education and were prescribed antidepressants at the discretion of their provider . The primary outcome measure was depression response , defined as a Hamilton Depression Inventory score < 8 ( remission ) or a decrease from baseline of at least 50 % at 12 weeks . Results — Intervention and usual care groups did not differ on any key baseline measures . Both depression response ( 51 % versus 30 % , P=0.005 ) and remission ( 39 % versus 23 % , P=0.01 ) were more likely in the Activate-Initiate-Monitor intervention than in the usual care group . This difference in depression scores was present by 6 weeks and persisted through the 12-week assessment . Serious adverse events did not differ between the 2 groups . Conclusion — The Activate-Initiate-Monitor care management model is significantly more effective than usual care in improving depression outcomes in patients with poststroke depression OBJECTIVE To examine the change in women ’s self-reported physical symptoms over 2 time points in relation to intimate partner violence ( IPV ) exposure . DESIGN Prospect i ve interview study of 267 women recruited from 8 health care setting s and surrounding communities in Metropolitan Boston . METHODS We created sums of somatic symptoms at 2 separate time points ( a mean of 9.5 months apart ) using items from a modified PHQ-15 . A measure of symptom change was computed to measure the net change in symptoms over time . A negative score indicated reduction in total symptoms , or improvement . Exposure to IPV was measured at both time points . RESULTS Women who reported ongoing IPV across both time points experienced an increase in their overall physical symptoms compared to women with past abuse ( p = .0054 ) and no abuse ( p = .0006 ) . In multivariate regression analysis , ongoing IPV at both time points was a statistically significant predictor of symptom change . This relationship persisted even after controlling for age , race , education , depression , self-report of co-morbid illness , and history of child abuse and prior sexual assault ( p = .0076 ) . CONCLUSIONS Women exposed to ongoing IPV report increased physical symptoms over time . Clinicians should consider the possibility of IPV in patients who remain persistently symptomatic over time in addition to employing more traditional means of detecting IPV Context Most successful disease management interventions for depression care have required intensive involvement of care managers or mental health specialists . Contribution The authors r and omly assigned 41 primary care physicians from 5 clinics to receive either depression decision support or usual care . Depression decision support was provided by a team that included a psychiatrist and a nurse care manager and involved an initial telephone contact , patient education , monthly record review , and sending a progress report to primary care physicians every 3 months . Depression severity improved equally in both groups over 12 months , despite evidence that intervention clinicians delivered more depression-related services . Implication s Decision support improved processes of depression care but not outcomes . The Editors Depression is a common problem worldwide . According to projections from the World Health Organization ( WHO ) , depression will be the second leading cause of disability in the developed world by 2020 ( 1 ) . One in 10 primary care patients meets criteria for major depression ( 2 ) , yet underrecognition and undertreatment are common ( 3 , 4 ) . Untreated depression is associated with increased deaths , adverse medical outcomes , deficits in function and well-being , and increased use of health services ( 3 , 59 ) . Multifaceted , collaborative interventions have been shown to improve depression-related outcomes in primary care ( 1022 ) . These interventions include decision support for clinicians , self-management support for patients , clinical information systems modifications , and care management . Care management typically consists of patient education and activation , symptom and treatment adherence monitoring , and self-management reinforcement ( 23 ) . Most collaborative depression interventions have relied on intensive involvement of care managers and specialists , usually shifting responsibility and workload toward mental health or research teams . Clinical systems may not be capable of sustaining this level of intensity . We therefore developed a multifaceted depression decision support intervention , which was design ed to optimize primary care clinicians ' abilities to treat depression without adding substantial new re sources . We aim ed to determine the effect of depression decision support on clinical outcomes and processes of care among patients with depression in a Veterans Affairs ( VA ) primary care setting . Methods Design Overview Our clinician-level , cluster r and omized , controlled trial studied depression decision support versus usual care . We r and omly assigned clinicians to either group and nested patients within clinician group assignment . We recruited participants between July 2002 and October 2003 from 5 primary care clinics of a VA medical center and followed patients for 12 months . The local institutional review board approved the study , and all patients and clinicians gave written informed consent . Setting Approximately 25000 veterans were treated during the study period in the 5 primary care clinics ( 3 urban and 2 rural clinics ) . Mental health clinicians are available on site in all clinics to provide consultation and brief treatment . A separate , more traditional mental health clinic serves approximately 8000 patients with chronic mental illnesses . Participants Full- and part-time staff physicians , fellows , physician assistants , and nurse practitioners were eligible to participate , and 41 ( 95 % ) of 43 eligible clinicians agreed to participate . To decrease variability in baseline depression-related knowledge and skills , we invited all clinicians to participate in the MacArthur Foundation depression education program ( 2427 ) before r and omization . In two 4-hour sessions , the program addresses communication skills and knowledge related to recognizing and managing depression . All patients of participating clinicians were eligible for the study . Research assistants review ed medical records of patients with upcoming primary care appointments ( within 4 to 6 weeks ) . They excluded patients who had received treatment from mental health specialists within the previous 6 months ; who had received a diagnosis of psychotic disorder , dementia , or bipolar disorder ; or who were considered to be terminally ill . They mailed study introduction letters to nonexcluded patients . The letters informed the patients that the research team would call them within 2 weeks unless they declined screening by notifying the study office . Telephone screening measures included the Patient Health Question naire ( PHQ-9 ) ( 28 ) and the Short Blessed Test screening for dementia ( 29 ) . We invited patients with PHQ-9 scores of 10 to 25 ( moderate to severe depression ) ( 30 ) to attend in-person enrollment interviews . We referred patients with PHQ-9 scores greater than 25 ( very severe depression ) or active dangerous ideation for urgent care , and we excluded them from participation . Enrollment interviews were scheduled within 2 weeks of primary care visits and usually took place the same day . The primary inclusion criterion was a repeated PHQ-9 score of 10 to 25 or a Hopkins Symptom Checklist-20 ( SCL-20 ) ( 31 ) score of 1.0 or greater at the enrollment interview . Of the 5434 patients who were mailed study introduction letters , 3500 ( 64 % ) were reached by telephone and were offered screening ( Figure 1 ) , and 3103 ( 89 % ) of those patients completed telephone screening . Of these patients , 560 ( 18 % ) had PHQ-9 scores between 10 and 25 and were eligible for in-person enrollment interviews . Of the 402 patients who completed the enrollment interviews , 375 had repeated PHQ-9 scores between 10 and 25 or SCL-20 scores of 1.0 or greater and were enrolled in the study . Figure 1 . Study flow chart . PHQ-9 = Patient Health Question naire . R and omization After clinicians participated in the MacArthur Foundation depression education program , we r and omly assigned clinicians to receive depression decision support or to usual care . Patients were nested within clinician assignment group . A stratified technique used a r and om-number generator to produce equivalent distributions across clinician type ( physician vs. physician 's assistant or nurse practitioner ) and clinic site . Clinicians in one clinic with substantial variation in caseload size were ranked by caseload and underwent block r and omization . Intervention The depression decision support team consisted of 1 psychiatrist who was assigned up to 4 hours per week and 1 nurse care manager who was assigned up to 8 hours per week . Within 1 to 2 weeks after enrollment , the depression decision support care manager attempted to call each intervention patient to provide education , explore barriers , emphasize adherence to treatment , and encourage communication with clinicians about depression ( Table 1 ) . Supplemental educational material s were mailed to all intervention patients . During the telephone call , patients were invited to attend a 2-hour group depression education program led by the care manager or a depression education class offered by the mental health team in 1 of the urban clinics . Aside from this single early telephone contact , only rare additional contact between the depression decision support care manager and patients was expected . Table 1 . Summary of Depression Decision Support Intervention and Usual Care Components The depression decision support team met weekly and review ed PHQ-9 scores ( collected by the research team at baseline and at 1 , 3 , 6 , 9 , and 12 months ) and medication and appointment data from the medical records . The team review ed each intervention patient record at least monthly . Using a data base , the depression decision support care manager compiled symptom severity and adherence data , posttraumatic stress disorder and alcohol screening results ( obtained from routine clinic screening ) , and treatment recommendations into a treatment progress report . The report was mailed to each intervention clinician for all of their enrolled patients quarterly . If primary care clinicians did not respond to initial PHQ-9 scores greater than 15 or when patients ' depression did not adequately improve ( PHQ-9 score>10 at 3 months or PHQ-9 score>5 at 6 , 9 , or 12 months ) , the depression decision support team review ed records again and then contacted clinicians or their nurses to discuss treatment strategies or to offer consultation . When the depression decision support team and primary care clinician agreed that psychiatric consultation might be helpful , the psychiatrist arranged a visit . When ongoing mental health specialty care was indicated , the depression decision support team facilitated a referral . Usual Care Clinicians received notifications when their patients enrolled in the study and were provided baseline PHQ-9 scores ( Table 1 ) . Usual care clinicians had access to all initial and follow-up PHQ-9 scores ( available in the medical record ) , but usual care clinicians did not receive notifications , reminders , or recommendations about scores from the depression decision support team . Usual care clinicians and their patients also had access to mental health services , including on-site mental health teams . Outcomes and Measurements Blinded research assistants collected baseline patient data in person and PHQ-9 scores ( at 1 , 3 , 6 , 9 , and 12 months ) and outcome data ( at 6 and 12 months ) by telephone . When patients could not be reached by telephone , research assistants mailed question naires to them . Baseline measures included demographic information , Medical Outcomes Study 36-item Short Form for Veterans ( SF-36V ) scores for health-related quality of life ( 32 ) , SCL-20 score for depression severity ( 31 ) , Alcohol Use Disorders Identification Test score ( 33 , 34 ) , PHQ scores for anxiety and panic disorders ( 35 ) , Posttraumatic Stress Disorder Checklist score ( 36 ) , Medical Outcomes Study pain effects score ( 37 ) , and the dysthymia stem from the WHO Composite International Diagnostic Interview ( 38 ) . The PHQ-9 from the enrollment interview was used to BACKGROUND Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer , but evidence to guide its management is scarce . We aim ed to assess the efficacy and cost of a nurse-delivered complex intervention that was design ed to treat major depressive disorder in patients who have cancer . METHODS We did a r and omised trial in a regional cancer centre in Scotl and , UK . 200 out patients who had cancer with a prognosis of greater than 6 months and major depressive disorder ( identified by screening ) were eligible and agreed to take part . Their mean age was 56.6 ( SD 11.9 ) years , and 141 ( 71 % ) were women . We r and omly assigned 99 of these participants to usual care , and 101 to usual care plus the intervention , with minimisation for sex , age , diagnosis , and extent of disease . The intervention was delivered by a cancer nurse at the centre over an average of seven sessions . The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale ( range 0 to 4 ) at 3 months after r and omisation . Analysis was by intention to treat . This trial is registered as IS RCT N84767225 . FINDINGS Primary outcome data were missing for four patients . For 196 patients for whom we had data at 3 months , the adjusted difference in mean Symptom Checklist-20 depression score , between those who received the intervention and those who did not , was 0.34 ( 95 % CI 0.13 - 0.55 ) . This treatment effect was sustained at 6 and 12 months . The intervention also improved anxiety and fatigue but not pain or physical functioning . It cost an additional pound sterling 5278 ( US$ 10 556 ) per quality -adjusted life-year gained . INTERPRETATION The intervention-Depression Care for People with Cancer-offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible , acceptable , and potentially cost effective CONTEXT Pain and depression are the most common physical and psychological symptoms in primary care , respectively . Moreover , they co-occur 30 % to 50 % of the time and have adverse effects on quality of life , disability , and health care costs . OBJECTIVE To determine if a combined pharmacological and behavioral intervention improves both depression and pain in primary care patients with musculoskeletal pain and comorbid depression . DESIGN , SETTING , AND PATIENTS R and omized controlled trial ( Stepped Care for Affective Disorders and Musculoskeletal Pain [ SCAMP ] ) conducted at 6 community-based clinics and 5 Veterans Affairs general medicine clinics in Indianapolis , Indiana . Recruitment occurred from January 2005 to June 2007 and follow-up concluded in June 2008 . The 250 patients had low back , hip , or knee pain for 3 months or longer and at least moderate depression severity ( Patient Health Question naire 9 score > or = 10 ) . INTERVENTION Patients were r and omly assigned to the intervention ( n = 123 ) or to usual care ( n = 127 ) . The intervention consisted of 12 weeks of optimized antidepressant therapy ( step 1 ) followed by 6 sessions of a pain self-management program over 12 weeks ( step 2 ) , and a continuation phase of therapy for 6 months ( step 3 ) . MAIN OUTCOME MEASURES Depression ( 20-item Hopkins Symptom Checklist ) , pain severity and interference ( Brief Pain Inventory ) , and global improvement in pain at 12 months . RESULTS At 12 months , 46 of the 123 intervention patients ( 37.4 % ) had a 50 % or greater reduction in depression severity from baseline compared with 21 of 127 usual care patients ( 16.5 % ) ( relative risk [ RR ] , 2.3 ; 95 % confidence interval [ CI ] , 1.5 - 3.2 ) , corresponding to a much lower number of patients with major depression ( 50 [ 40.7 % ] vs 87 [ 68.5 % ] , respectively ; RR , 0.6 [ 95 % CI , 0.4 - 0.8 ] ) . Also , a clinical ly significant ( > or = 30 % ) reduction in pain was much more likely in intervention patients ( 51 intervention patients [ 41.5 % ] vs 22 usual care patients [ 17.3 % ] ; RR , 2.4 [ 95 % CI , 1.6 - 3.2 ] ) , as was global improvement in pain ( 58 [ 47.2 % ] vs 16 [ 12.6 % ] , respectively ; RR , 3.7 [ 95 % CI , 2.3 - 6.1 ] ) . More intervention patients also experienced benefits in terms of the primary outcome , which was a combined improvement in both depression and pain ( 32 intervention patients [ 26.0 % ] vs 10 usual care patients [ 7.9 % ] ; RR , 3.3 [ 95 % CI , 1.8 - 5.4 ] ) . CONCLUSION Optimized antidepressant therapy followed by a pain self-management program result ed in substantial improvement in depression as well as moderate reductions in pain severity and disability . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118430 CONTEXT Few depressed older adults receive effective treatment in primary care setting s. OBJECTIVE To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) collaborative care management program for late-life depression . DESIGN R and omized controlled trial with recruitment from July 1999 to August 2001 . SETTING Eighteen primary care clinics from 8 health care organizations in 5 states . PARTICIPANTS A total of 1801 patients aged 60 years or older with major depression ( 17 % ) , dysthymic disorder ( 30 % ) , or both ( 53 % ) . INTERVENTION Patients were r and omly assigned to the IMPACT intervention ( n = 906 ) or to usual care ( n = 895 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education , care management , and support of antidepressant management by the patient 's primary care physician or a brief psychotherapy for depression , Problem Solving Treatment in Primary Care . MAIN OUTCOME MEASURES Assessment s at baseline and at 3 , 6 , and 12 months for depression , depression treatments , satisfaction with care , functional impairment , and quality of life . RESULTS At 12 months , 45 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline compared with 19 % of usual care participants ( odds ratio [ OR ] , 3.45 ; 95 % confidence interval [ CI ] , 2.71 - 4.38 ; P<.001 ) . Intervention patients also experienced greater rates of depression treatment ( OR , 2.98 ; 95 % CI , 2.34 - 3.79 ; P<.001 ) , more satisfaction with depression care ( OR , 3.38 ; 95 % CI , 2.66 - 4.30 ; P<.001 ) , lower depression severity ( range , 0 - 4 ; between-group difference , -0.4 ; 95 % CI , -0.46 to -0.33 ; P<.001 ) , less functional impairment ( range , 0 - 10 ; between-group difference , -0.91 ; 95 % CI , -1.19 to -0.64 ; P<.001 ) , and greater quality of life ( range , 0 - 10 ; between-group difference , 0.56 ; 95 % CI , 0.32 - 0.79 ; P<.001 ) than participants assigned to the usual care group . CONCLUSION The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practice Background Whether the acute outcomes of major depressive disorder ( MDD ) treated in primary ( PC ) or specialty care ( SC ) setting s are different is unknown . Objective To compare the treatment and outcomes for depressed out patients treated in primary versus specialty setting s with citalopram in the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) study ( www.star-d.org ) , a broadly inclusive effectiveness trial . Design Open clinical trial with citalopram for up to 14 weeks at 18 primary and 23 specialty sites . Participants received measurement-based care with 5 recommended treatment visits , manualized pharmacotherapy , ongoing support and guidance by a clinical research coordinator , the use of structured evaluation of depressive symptoms and side effects at each visit , and a central ized treatment monitoring and feedback system . Participants A total of 2,876 previously established out patients in primary ( n = 1091 ) or specialty ( n = 1785 ) with nonpsychotic depression who had at least 1 post-baseline measure . Measurements and Main Results Remission ( Hamilton Depression Rating Scale for Depression [ Hamilton ] or 16-item Quick Inventory of Depressive Symptomatology-Self-Rated [ QIDS-SR16 ] ) ; response ( QIDS-SR16 ) ; time to first remission ( QIDS-SR16 ) . Remission rates by Hamilton ( 26.6 % PC vs 28.0 % SC , p = .40 ) and by QIDS-SR16 ( 32.5 % PC vs 33.1 % SC , p = .78 ) and response rates by QIDS-SR16 ( 45.7 % PC vs 47.6 % SC , p = .33 ) were not different . For those who reached remission or response at exit , the time to remission ( 6.2 weeks PC vs 6.9 weeks SC , p = .12 ) and to response ( 5.5 weeks PC vs 5.4 weeks SC , p = .97 ) did not differ by setting . Conclusions Identical remission and response rates can be achieved in primary and specialty setting s when identical care is provided OBJECTIVE In response to health concerns of military members about deployment and other service-related exposures , the Department of Defense ( DoD ) initiated the largest prospect i ve study ever undertaken in the U.S. military . STUDY DESIGN AND SETTING The Millennium Cohort uses a phased enrollment strategy to eventually include more than 100,000 U.S. service members who will be followed up through the year 2022 , even after leaving military service . Subjects will be linked to DoD and Veterans Affairs data bases and surveyed every 3 years to obtain objective and self-reported data on exposures and health outcomes . RESULTS The first enrollment phase was completed in July 2003 and result ed in 77,047 consenting participants , well representative of both active-duty and Reserve/Guard forces . This report documents the baseline characteristics of these Cohort members , describes traditional , postal , and Web-based enrollment methods ; and describes the unique challenges of enrolling , retaining , and following such a large Cohort . CONCLUSION The Millennium Cohort was successfully launched and is becoming especially relevant , given current deployment and exposure concerns . The Cohort is representative of the U.S. military and promises to provide new insight into the long-term effects of military occupations on health for years to come OBJECTIVE This article describes the r and omized clinical trial methodology for a population -based study of oncology patients receiving cancer care in a public sector medical center . The primary goal is to test the effectiveness of socioculturally tailored collaborative care intervention in improving depression and quality of life outcomes among low-income ethnic minority patients with major depression and cancer . METHODS The Patient Health Question naire ( PHQ-9 ) depression scale was used to identify patients meeting criteria for major depression ( one cardinal depression symptom plus a PHQ-9 score of > or = 10 ) . Study -eligible patients were > /=90 days from cancer diagnosis who were receiving acute cancer treatment or follow-up care in oncology clinics . Patients with advanced disease limiting life expectancy to < 6 months , acutely suicidal or on antipsychotic medication were excluded . Allowing for attrition due to death or loss to follow-up , the study was powered at the 80 % level to detect a 20 % difference between study arms in the proportion of patients with > /=50 % reduction in PHQ-9 symptoms at 12 months . RESULTS Of 2330 patients screened , 23.2 % met criteria . An 82.4 % enrollment rate result ed in 446 primarily women being recruited and r and omized to intervention or usual care . CONCLUSION The study applies methods used in primary care depression trials with adaptations for oncology care clinics and for low-income minority patients In a pilot study , 55 low-income Latina patients with breast or cervical cancer and comorbid depression were r and omly assigned to receive collaborative care as part of the Multifaceted Oncology Depression Program or usual care . Relative to patients in the usual care condition , patients receiving collaborative care were more likely to show > or=50 % improvement in depressive symptoms as measured by the Personal Health Question naire ( OR=4.51 , 95 % CI=1.07 - 18.93 ) . Patients in the collaborative care program were also more likely to show improvement in emotional well-being ( increase of 2.15 ) as measured by the Functional Assessment of Cancer Therapy Scale than were those receiving usual care ( decrease of 0.50 ) ( group difference=2.65 , 95 % CI : 0.18 - 5.12 ) . Despite health system , provider , and patient barriers to care , these initial results suggest that patients in public sector oncology clinics can benefit from onsite depression treatment BACKGROUND Most diagnostic interviews depend on recall of past symptoms and may be vulnerable to recall bias . The objective of this study was to describe the epidemiology of major depression using an approach that is less reliant on recall using an assessment scale , the 9-item Brief Patient Health Question naire ( PHQ-9 ) . The pattern observed is relevant both to underst and ing major depression epidemiology and to assessing a possible role for the PHQ-9 as a screening instrument . METHOD R and om digit dialing was used to select a sample of 3304 community residents . Each respondent was assessed with a baseline interview followed by a series of 6 subsequent follow-up interviews 2 weeks apart . RESULTS Prevalence was between 2.5 % and 3.3 % during each interview , consistent with prior reports . The incidence of new episodes was surprisingly high , and many of the episodes were brief . Similarly , high rates of recovery ( according to PHQ-9 scoring ) were seen early in follow-up but declined subsequently . Episodes of major depression detected by the PHQ-9 tended to be preceded and followed by elevated levels of depressive symptoms . CONCLUSIONS The long-st and ing episodes of major depression typical of clinical practice appear to represent a minority of episodes occurring in the community . These results suggest that , in general population screening applications , the PHQ-9 will identify many respondents having brief and perhaps self-limited episodes . Although some episodes are characterized by large increases in symptoms , many respondents appear to move above and below the diagnostic threshold as a result of small changes in their symptom levels . Efforts to develop more effective approaches to screening may benefit from severity-based decision rules and serial measurement strategies OBJECTIVE To determine the validity of a two- question case-finding instrument for depression as compared with six previously vali date d instruments . DESIGN The test characteristics of a two- question case-finding instrument that asks about depressed mood and anhedonia were compared with six common case-finding instruments , using the Quick Diagnostic Interview Schedule as a criterion st and ard for the diagnosis of major depression . SETTING Urgent care clinic at the San Francisco Department of Veterans Affairs Medical Center . PARTICIPANTS Five hundred thirty-six consecutive adult patients without mania or schizophrenia . MEASUREMENTS AND MAIN RESULTS Measurements were two questions from the Primary Care Evaluation of Mental Disorders patient question naire , both the long and short forms of the Center for Epidemiologic Studies Depression Scale , both the long and short forms of the Book Depression Inventory , the Symptom-Driven Diagnostic System for Primary Care , the Medical Outcomes Study depression measure , and the Quick Diagnostic Interview Schedule . The prevalence of depression , as determined by the st and ardized interview , was 18 % ( 97 of 536 ) . Overall , the case-finding instruments had sensitivities of 89 % to 96 % and specificities of 51 % to 72 % for diagnosing major depression . A positive response to the two-item instrument had a sensitivity of 96 % ( 95 % confidence interval [ CI ] , 90 - 99 % ) and a specificity of 57 % ( 95 % CI 53 - 62 % ) . Areas under the receiver operating characteristic curves were similar for all of the instruments , with a range of 0.82 to 0.89 . CONCLUSIONS The two- question case-finding instrument is a useful measure for detecting depression in primary care . It has similar test characteristics to other case-finding instruments and is less time-consuming BACKGROUND Screening of patients for common mental disorders ( CMDs ) is needed in primary -care management programmes . This study aim ed to compare the screening properties of five widely used question naires . METHOD Adult attenders in five primary -care setting s in India were recruited through systematic sampling . Four question naires were administered , in pairs , in r and om order to participants : the General Health Question naire ( GHQ , 12 items ) ; the Primary Health Question naire ( PHQ , nine items ) ; the Kessler Psychological Distress Scale ( K10 , 10 items ) , and from which we could extract the score of the shorter 6-item K6 ; and the Self-Reporting Question naire ( SRQ , 20 items ) . All participants were interviewed with a structured lay diagnostic interview , the Revised Clinical Interview Schedule ( CIS-R ) . RESULTS Complete data were available for 598 participants ( participation rate 99.3 % ) . All five question naires showed moderate to high discriminating ability ; the GHQ and SRQ showed the best results . All five showed moderate to high degrees of correlation with one another , the poorest being between the two shortest question naires , K6 and PHQ . All five had relatively good internal consistency . However , the positive predictive value ( PPV ) of the question naires compared with the diagnostic interview ranged from 51 % to 77 % at the optimal cut-off scores . CONCLUSIONS There is little difference in the ability of these question naires to identify cases accurately , but none showed high PPVs without a considerable compromise on sensitivity . Hence , the choice of an optimum cut-off score that yields the best balance between sensitivity and PPV may need to be tailored to individual setting s , with a higher cut-off being recommended in re source -limited primary -care setting Objectives : The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions , singly and together . Methods : A r and om sample of Kaiser Permanente patients who visited a primary care clinic was mailed a question naire assessing major depressive disorder ( MDD ) , chronic pain , pain-related disability , somatic symptom severity , panic disorder , other anxiety , probable alcohol abuse , and health-related quality of life ( HRQL ) . Instruments included the Patient Health Question naire , SF-8 , and Grade d Chronic Pain Question naire . A total of 5808 patients responded ( 54 % of those eligible to participate ) . Results : Among those with MDD , a significantly higher proportion reported chronic ( i.e. , nondisabling or disabling ) pain than those without MDD ( 66 % versus 43 % , respectively ) . Disabling chronic pain was present in 41 % of those with MDD versus 10 % of those without MDD . Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL , greater somatic symptom severity , and higher prevalence of panic disorder than other respondents . The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level . Compared with participants without MDD , the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level . Conclusions : Chronic pain is common among those with MDD . Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone . MDD = major depressive disorder ; HRQL = health-related quality of life ; HMO = health maintenance organization ; PHQ = Patient Health Question naire ; GCPS = Grade d Chronic Pain Scale ; CP = chronic pain ; DCP = disabling chronic pain ; GAD = generalized anxiety disorder ; SCID = Structured Clinical Interview for DSM-III-R ; PRIME-MD = Primary Care Evaluation of Mental Disorders ; CI = confidence interval ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders , Third Edition Revised Background Somatoform disorders are an important factor in functional disability and role impairment , though their independent contribution to disability has been unclear because of prevalent medical and psychiatric comorbidity . Objectives To assess the extent of the overlap of somatization with other psychiatric disorders and medical problems , to compare the functional disability and role impairment of somatizing and non-somatizing patients , and to determine the independent contribution of somatization to functional disability and role impairment . Design Patients were surveyed with self-report question naires assessing somatization , psychiatric disorder , and role impairment . Medical morbidity was indexed with a computerized medical record audit . Participants Consecutive adults making scheduled visits to their primary care physicians at two hospital-affiliated primary care practice s on r and omly chosen days . Measurements Intermediate activities of daily living , social activities , and occupational disability . Results Patients with somatization , as well as those with serious medical and psychiatric illnesses , had significantly more impairment of activities of daily life and social activities . When these predictors were considered simultaneously in a multivariable regression , the association with somatization remained highly significant and was comparable to or greater than many major medical conditions . Conclusions Patients with somatization had substantially greater functional disability and role impairment than non-somatizing patients . The degree of disability was equal to or greater than that associated with many major , chronic medical disorders . Adjusting the results for psychiatric and medical co-morbidity had little effect on these findings R and omized controlled trials have demonstrated the efficacy and cost-effectiveness of using treatment models for major depression in primary care setting s. Nonetheless , translating these models into enduring changes in routine primary care has proved difficult . Various health system and organizational barriers prevent the integration of these models into primary care setting s. This article discusses barriers to introducing and sustaining evidence -based depression management services in community-based primary care practice s and suggests organizational and financial solutions based on the Robert Wood Johnson Foundation Depression in Primary Care Program . It focuses on strategies to improve depression care in medical setting s based on adaptations of the chronic care model and discusses the challenges of implementing evidence -based depression care given the structural , financial , and cultural separation between mental health and general medical care Background : Re-Engineering Systems for Primary Care Treatment of Depression ( RESPECT-D ) sought to improve patient outcomes by disseminating the 3-component model of depression management . The purpose of this study was to determine whether an integrated model of depression management continued to be used by primary care clinicians after the end of a r and omized controlled trial ( RCT ) . Methods : A descriptive evaluation was conducted at 2 time points . First , during a 12-month period after the end of the RESPECT-D RCT when referrals to care management were determined for each of the 5 participating health care organizations . Second , 3 years after the RCT ended , when clinicians were surveyed about use of the 3-component model . Results : Three organizations continued to support the model with minimal modification . One made a major modification to it and one did not continue to support it . In the 12 months after the RCT , 1039 care management referrals were made . Seventy-one percent of RCT clinicians ( n = 92 ) completed the follow-up survey . Of these , 87 % reported using the Patient Health Question naire-9 ; 58.9 % reported availability of care management and 45.1 % reported availability of informal psychiatry consultation . Conclusion : Practical clinical interventions can be sustained in primary care practice after the completion of an RCT . Additional re sources may be needed to sustain and spread the program A test-retest reliability study of the Structured Clinical Interview for DSM-III-R was conducted on 592 subjects in four patient and two nonpatient sites in this country as well as one patient site in Germany . For most of the major categories , kappa s for current and lifetime diagnoses in the patient sample s were above .60 , with an overall weighted kappa of .61 for current and .68 for lifetime diagnoses . For the non patients , however , agreement was considerably lower , with a mean kappa of .37 for current and .51 for lifetime diagnoses . These values for the patient and nonpatient sample s are roughly comparable to those obtained with other structured diagnostic instruments . Sources of diagnostic disagreement , such as inadequate training of interviewers , information variance , and low base rates for many disorders , are discussed BACKGROUND Two instruments commonly used in primary care research to measure depressive severity are the Patient Health Question naire-9 ( PHQ-9 ) and the Hopkins Symptom Checklist-20 ( HSCL-20 ) . However , there is little information regarding the relationship between clinical information derived from these scales . The present study investigates the psychometric properties of the PHQ-9 and HSCL-20 , determines the degree of instrument concordance , and describes the factor structure of the HSCL-20 . METHODS A secondary data analysis from a r and omized controlled trial was performed . A total of 405 primary care patients with major depressive disorder and /or dysthymia were administered the PHQ-9 and the HSCL-20 when recruited for the study . RESULTS Good internal consistency reliability estimates were obtained for both scales ( PHQ-9 alpha=0.803 ; HSCL-20 alpha=0.837 ) . All PHQ-9 inter-item and corrected item-total correlations showed that no item detracted from overall scale functioning . HSCL-20 items assessing overeating , poor appetite , and sexual interest were poorly correlated with other items and with the total scale score . A positive , moderate strength relationship was found between the instruments ( r=0.54 , p<0.0001 ) . Exploratory factor analysis of the HSCL-20 yielded a six-factor structure , which accounted for almost 63 % of the variance in total score . The largest contribution to common variance in the scale was provided by an " anxiety and self-reproach " factor . CONCLUSIONS PHQ-9 and HSCL-20 total scores were moderately correlated . Although the HSCL-20 is utilized as a measure of depression severity , it may lack sufficient specificity to be an accurate reflection of depression status per se Preliminary data suggest that hypericum extract LI160 is effective in atypical depression . Reported is the outcome of an 8-week double-blind , placebo-controlled , r and omized trial of 600 mg LI160 vs. placebo in patients with vegetative features of atypical depression , i.e. hyperphagia or hypersomnia . One-hundred ( 100 ) patients with mild and 100 patients with moderate severity of a major depression according to ICD-10 were r and omized . Patients needed to meet a score of 2 in at least one of the items 22 - 26 of the Hamilton-Depression-Rating-Scale ( HAM-D ) 28-item version and episode duration of at least 3 months . The primary outcome variable was the relative change of the HAM-D(17 ) from Baseline . Secondary outcome variables were the depression sub-score of the Patient Health Question naire ( PHQ-9 ) , the Clinical Global Impression ( CGI ) , a patient 's satisfaction scale , the Hamilton-Anxiety-Scale ( HAM-A ) and the sum score of atypical vegetative symptoms of the HAM-D(28 ) . The percentage reduction of the HAM-D(17 ) for LI160 compared to placebo approached statistical significance ( p=0.051 ) in the Full Analysis Set (FAS)- population . Using the conventional criterion of the absolute reduction of the HAM-D(17 ) significance was achieved ( p<0.05 ) . No significant benefit could be observed for the sum score of the atypical vegetative items of the HAM-D(28 ; ) however , the sum score of the hypersomnia items ( items 22 - 24 ) showed a significant superiority for LI160 . The HAM-A , PHQ-9 , and CGI-I scales demonstrated superiority of LI160 ( p<0.01 ) . Confining the analysis to moderately depressed patients , a highly significant benefit for the primary outcome variable was revealed . The study supports the beneficial effect of LI160 in depression with atypical features and the validity of the definition of atypical depression on the basis of reversed vegetative signs . Further , it identifies the PHQ-9 as a useful outcome variable in this population Background : Although effective treatment of depressed patients requires regular follow-up contacts and symptom monitoring , an efficient method for assessing treatment outcome is lacking . We investigated responsiveness to treatment , reproducibility , and minimal clinical ly important difference of the Patient Health Question naire-9 ( PHQ-9 ) , a st and ard instrument for diagnosing depression in primary care . Methods : This study included 434 intervention subjects from the IMPACT study , a multisite treatment trial of late-life depression ( 63 % female , mean age 71 years ) . Changes in PHQ-9 scores over the course of time were evaluated with respect to change scores of the SCL-20 depression scale as well as 2 independent structured diagnostic interviews for depression during a 6-month period . Test-retest reliability and minimal clinical ly important difference were assessed in 2 subgroups of patients who completed the PHQ-9 twice exactly 7 days apart . Results : The PHQ-9 responsiveness as measured by effect size was significantly greater than the SCL-20 at 3 months ( −1.3 versus −0.9 ) and equivalent at 6 months ( −1.3 versus −1.2 ) . With respect to structured diagnostic interviews , both the PHQ-9 and the SCL-20 change scores accurately discriminated patients with persistent major depression , partial remission , and full remission . Test-retest reliability of the PHQ-9 was excellent , and its minimal clinical ly important difference for individual change , estimated as 2 st and ard errors of measurement , was 5 points on the 0 to 27 point PHQ-9 scale . Conclusions : Well-vali date d as a diagnostic measure , the PHQ-9 has now proven to be a responsive and reliable measure of depression treatment outcomes . Its responsiveness to treatment coupled with its brevity makes the PHQ-9 an attractive tool for gauging response to treatment in individual patient care as well as in clinical research CONTEXT Selective serotonin reuptake inhibitors ( SSRIs ) are the most commonly prescribed class of antidepressant , yet it is not known whether one SSRI is more effective than another . OBJECTIVE To compare the effectiveness of 3 SSRIs ( paroxetine , fluoxetine , and sertraline ) in depressed primary care patients . DESIGN Open-label , r and omized , intention-to-treat trial , with patient enrollment occurring in April-November 1999 . SETTING Thirty-seven clinics in 2 US primary care research networks . PATIENTS A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 189 ) , fluoxetine ( n = 193 ) , or sertraline ( n = 191 ) for 9 months . Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI . MAIN OUTCOME MEASURES The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) Mental Component Summary score ( range , 0 - 100 ) , compared across treatment groups at 1 , 3 , 6 , and 9 months . Secondary outcomes included other depression and psychological measures , multiple measures of social and work functioning , and other domains of health-related quality of life , such as physical functioning , concentration and memory , vitality , bodily pain , sleep , and sexual functioning . RESULTS Follow-up interviews were successfully completed in 94 % of patients at 1 month , 87 % at 3 months , 84 % at 6 months , and 79 % at 9 months . Responses to the 3 SSRIs were comparable on all measures and at all time points . The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group , + 15.1 in the fluoxetine group , and + 17.4 in the sertraline group . The drugs were also associated with similar incidences of adverse effects and discontinuation rates . CONCLUSIONS The SSRI antidepressants paroxetine , fluoxetine , and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial CONTEXT Somatoform disorders are an important determinant of medical care utilization , but their independent effect on utilization is difficult to determine because somatizing patients frequently have psychiatric and medical comorbidity . OBJECTIVES To assess the extent of the overlap of somatization with other psychiatric disorders ; to compare the medical utilization of somatizing and nonsomatizing patients ; and to determine the independent contribution of somatization alone to utilization . DESIGN Patients were surveyed with self-report question naires assessing somatization and psychiatric disorder . Medical care utilization was obtained from automated encounter data for the year preceding the index visit . Medical morbidity was indexed with a computerized medical record audit . SETTING Two hospital-affiliated primary care practice s. PARTICIPANTS Consecutive adults making scheduled visits to their primary care physicians on r and omly chosen days . In all , 2668 question naires were distributed , and 1914 ( 71.7 % ) were returned . Of these , 1546 ( 80.8 % ) contained complete data and met eligibility criteria . MAIN OUTCOME MEASURES Medical care utilization and costs within our hospital system in the preceding 12 months . RESULTS Two hundred ninety-nine patients ( 20.5 % ) received a provisional diagnosis of somatization ; 42.3 % of these patients had no comorbid depressive or anxiety disorder . Somatizing patients , when compared with nonsomatizing patients , had more primary care visits ( mean [ SE ] , 4.90 [ 0.32 ] vs 3.43 [ 0.11 ] ; P<.001 ) ; more specialty visits ( mean [ SE ] , 8.13 [ 0.55 ] vs 4.90 [ 0.21 ] ; P<.001 ) ; more emergency department visits ( mean [ SE ] , 1.29 [ 0.15 ] vs 0.52 [ 0.036 ] ; P<.001 ) ; more hospital admissions ( mean [ SE ] , 0.32 [ 0.051 ] vs 0.13 [ 0.014 ] ; P<.001 ) ; higher inpatient costs ( mean [ SE ] , USD 3146 [ USD 380 ] vs USD 991 [ USD 193 ] ; P<.001 ) ; and higher outpatient costs ( mean [ SE ] , USD 3208 [ USD 180 ] vs USD 1771 [ USD 91 ] ; P<.001 ) . When these results were adjusted for the presence of comorbid anxiety and depressive disorders , major medical morbidity , and sociodemographic characteristics , patients with somatoform disorder still had more primary care visits ( P = .04 ) , more specialist visits ( P = .002 ) , more emergency department visits ( P<.001 ) , more hospital admissions ( P<.001 ) , more ambulatory procedures ( P<.001 ) , higher inpatient costs ( P<.001 ) , and higher outpatient costs ( P<.001 ) . When these findings are extrapolated to the national level , an estimated USD 256 billion a year in medical care costs are attributable to the incremental effect of somatization alone . CONCLUSIONS Patients with somatization had approximately twice the outpatient and inpatient medical care utilization and twice the annual medical care costs of nonsomatizing patients . Adjusting the findings for the presence of psychiatric and medical comorbidity had relatively little effect on this association OBJECTIVE Depression and pain are common comorbid conditions that have reciprocal adverse effects on disability and treatment outcomes . The objective of this article is to describe a study that tests the effectiveness of a stepped-care approach using a combined medication-behavioral intervention . METHOD Stepped Care for Affective Disorders and Musculoskeletal Pain ( SCAMP ) is an NIMH-sponsored r and omized clinical trial nested within a prospect i ve cohort study . A total of 250 patients with clinical ly significant depression ( PHQ-9 scores > or = 10 ) and musculoskeletal pain of the lower back or legs ( hip or knee ) and 250 nondepressed patients with similar pain are enrolled , with baseline and serial follow-up assessment s to be conducted over 12 months . The depressed patients are r and omized to either a stepped-care intervention group or a usual-care control group . Stepped-care patients receive 12 weeks of optimized antidepressant management ( Step 1 ) followed by six sessions of a pain self-management ( PSM ) program over the next 12 weeks ( Step 2 ) , all delivered by a nurse care manager who is supervised by a physician specialist . Approximately two thirds of the care manager contacts are by telephone . RESULTS The target sample of 500 subjects has been successfully enrolled , and r and omization of the depressed patients has result ed in balanced groups of patients with moderately severe pain and depression . Mean SCL-20 depression severity in the clinical trial group is 1.9 , with most meeting DSM-IV criteria for major depression ( 76.3 % ) and the rest having dysthymia only ( 18.4 % ) or minor depression ( 5.3 % ) . Pain is about equally distributed between lower back ( 53 % ) and hip or knee ( 47 % ) . A rational algorithmic approach to antidepressant selection and dosing , as well as an overview of the PSM program , is provided . CONCLUSIONS When completed , SCAMP will test whether optimized antidepressant management improves outcomes in patients with comorbid depression and pain and whether PSM produces additional benefits . The findings will be important for both primary care and mental health clinicians confronted by the prevalent depression-pain dyad PURPOSE To determine the effectiveness of the Alleviating Depression Among Patients With Cancer ( ADAPt-C ) collaborative care management for major depression or dysthymia . PATIENTS AND METHODS Study patients included 472 low-income , predominantly female Hispanic patients with cancer age > or= 18 years with major depression ( 49 % ) , dysthymia ( 5 % ) , or both ( 46 % ) . Patients were r and omly assigned to intervention ( n = 242 ) or enhanced usual care ( EUC ; n = 230 ) . Intervention patients had access for up to 12 months to a depression clinical specialist ( supervised by a psychiatrist ) who offered education , structured psychotherapy , and maintenance/relapse prevention support . The psychiatrist prescribed antidepressant medications for patients preferring or assessed to require medication . RESULTS At 12 months , 63 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline as assessed by the Patient Health Question naire-9 ( PHQ-9 ) depression scale compared with 50 % of EUC patients ( odds ratio [ OR ] = 1.98 ; 95 % CI , 1.16 to 3.38 ; P = .01 ) . Improvement was also found for 5-point decrease in PHQ-9 score among 72.2 % of intervention patients compared with 59.7 % of EUC patients ( OR = 1.99 ; 95 % CI , 1.14 to 3.50 ; P = .02 ) . Intervention patients also experienced greater rates of depression treatment ( 72.3 % v 10.4 % of EUC patients ; P < .0001 ) and significantly better quality -of-life outcomes , including social/family ( adjusted mean difference between groups , 2.7 ; 95 % CI , 1.22 to 4.17 ; P < .001 ) , emotional ( adjusted mean difference , 1.29 ; 95 % CI , 0.26 to 2.22 ; P = .01 ) , functional ( adjusted mean difference , 1.34 ; 95 % CI , 0.08 to 2.59 ; P = .04 ) , and physical well-being ( adjusted mean difference , 2.79 ; 95 % CI , 0.49 to 5.1 ; P = .02 ) . CONCLUSION ADAPt-C collaborative care is feasible and results in significant reduction in depressive symptoms , improvement in quality of life , and lower pain levels compared with EUC for patients with depressive disorders in a low-income , predominantly Hispanic population in public sector oncology clinics Context Anxiety and depression are both common in primary care patients , but much less attention has been paid to anxiety . Contribution The authors administered a 7-item anxiety scale ( Generalized Anxiety Disorder [GAD]-7 ) to 965 primary care patients , who also had a structured interview , to detect an anxiety disorder . Of these patients , 19.5 % had at least 1 anxiety disorder . Patients with anxiety had worse functional status , more disability days , and more physician visits , but 41 % were not being treated for any anxiety disorder . The GAD-7 had high sensitivity and good specificity for detecting a generalized anxiety disorder , panic disorder , social anxiety disorder , and posttraumatic stress disorder . Implication s Anxiety disorders are common , underrecognized , and undertreated , but they are easy to detect with a brief question naire . The Editors Anxiety and depression are the 2 most common mental health problems seen in the general medical setting ( 15 ) . Although increasing attention has been paid to anxiety , it still lags far behind depression in terms of research as well as clinical and public health efforts in screening , diagnosis , and treating affected individuals . This is unfortunate given the prevalence of anxiety and its substantial impact on patient functioning , work productivity , and health care costs ( 614 ) . More than 30 million Americans have a lifetime history of anxiety ( 15 ) , and anxiety disorders cost an estimated $ 42 billion dollars per year in the United States alone , counting direct and indirect costs ( 16 ) . The 4 most common anxiety disorders ( excluding simple phobias that seldom present clinical ly ) are generalized anxiety disorder , panic disorder , social anxiety disorder , and posttraumatic stress disorder ( PTSD ) ( 1723 ) . However , despite the substantial disability associated with each anxiety disorder and the availability of effective treatments , only a minority of patients ( 15 % to 36 % ) with anxiety are recognized in primary care ( 24 , 25 ) . In our paper , we analyze results from a large primary carebased anxiety study ( 26 ) to answer several questions . First , what is the prevalence of these 4 anxiety disorders , both individually and concurrent with one another ? Second , how do these disorders compare in functional impairment , health care use , and comorbid depressive and somatic symptom burden ? Third , how effective is a brief anxiety measure in screening for each disorder ? Compared with previous research , our study is particularly well-positioned to ascertain commonalities among anxiety diagnoses that are traditionally considered to be discrete and to determine whether a single measure can be used as a first step , common metric . This is especially salient for the busy , complex primary care setting , in which simplifying initial recognition of mental disorders may in fact make wider efforts at recognition more feasible . Methods Patient Sample The Patient Health Question naire ( PHQ ) anxiety study ( 26 ) was conducted to develop a short measure to assess generalized anxiety disorder . Patients were enrolled from a research network of 15 primary care sites ( 13 family practice and 2 internal medicine sites ) located in 12 states and administered central ly by Clinvest , Inc. , Springfield , Missouri , from November 2004 to June 2005 . The Generalized Anxiety Disorder (GAD)-7 scale was developed and vali date d in 2149 patients . In the original study , 2982 persons were invited to participate ; of these , 2740 ( 92 % ) completed the 4-page question naire and had no or minimal missing data ( 26 ) . To minimize sampling bias , consecutive patients were approached at each site in clinic sessions until the target quota for that week was achieved . Of the 2740 participants , the first 2149 were used for development and validation of the GAD-7 scale , whereas the last 591 were used to determine the testretest reliability of the scale . Of the 2149 patients in the validation group , 1654 agreed to a telephone interview , of whom 965 were r and omly selected to undergo this interview within 1 week of their clinic visit by 1 of 2 mental health professionals : a clinical psychologist ( with a PhD ) or a senior psychiatric social worker . Contact information was sent by fax to each interviewer , who shuffled the fax sheets received each day and then drew from the stack several participants to interview that day . The 965 interviewed patients comprise the study population for this paper , and compared with the 1184 participants who did not undergo a mental health professional interview , these were more often women ( 69 % vs. 63 % ; P= 0.003 ) and had slightly higher GAD-7 anxiety scores ( 5.7 vs. 5.1 ; P= 0.010 ) but were similar in age , race , and education . Of note , we only used data from the 1184 participants not undergoing a mental health professional interview to derive the GAD-7 ( 26 ) . The study was approved by the Sterling Institutional Review Board . Study Question naire Before seeing their physicians , patients completed a 4-page question naire that included the GAD-7 ( Appendix Figure ) . This scale was shown to have good internal and testretest reliability , as well as convergent , construct , criterion , procedural , and factorial validity for the diagnosis of generalized anxiety disorder ( 26 ) . Scores on the GAD-7 range from 0 to 21 ; scores of 5 , 10 , and 15 represent mild , moderate , and severe anxiety symptoms , respectively . The first 2 items of the GAD-7 represent core anxiety symptoms , and scores on this GAD-2 subscale range from 0 to 6 . Appendix Figure . The Generalized Anxiety Disorder (GAD)-7 scale . The first 2 items constitute the GAD-2 subscale . GAD-7 2006 Pfizer Inc. All rights reserved . Used with permission . The study question naire also included questions about age , sex , education , race or ethnicity , and marital status ; the Medical Outcomes Study Short Form-20 ( SF-20 ) , which measures functional status in 6 domains ( 27 ) ; the 10-item anxiety subscale from the Hopkins Symptom Checklist ( 28 ) ; the PHQ-8 depression scale ( 29 ) ; a 3-item version of the Social Phobia Inventory ( Mini-SPIN ) ( 30 ) ; the 5-item PHQ panic module ( 25 ) ; and the PHQ-15 somatic symptom scale ( 31 ) . Also , single-item global assessment s of anxiety , depression , and pain based on a scale of 0 ( none ) to 10 ( as bad as you can imagine ) were included . Finally , patients reported the number of physician visits and disability days during the previous 3 months . Structured Psychiatric Interview The 2 mental health professionals , while blinded to the results of the self-report research question naire , conducted structured psychiatric interviews by telephone to establish independent criteria -based diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) ( 32 ) . The interview consisted of the generalized anxiety disorder , social anxiety disorder , and PTSD sections of the Structured Clinical Interview for DSM-IV ( SCID ) ( 33 ) . Reinterview by telephone was used because of its feasibility in our multisite study and its demonstrated comparability with face-to-face research interviews ( 3436 ) . The 2 mental health professionals based diagnoses of generalized anxiety disorder and PTSD on the SCID interview . For generalized anxiety disorder , some questions were slightly modified to better assess each DSM-IV criterion . They based a diagnosis of social anxiety disorder on whether the patient met SCID diagnostic criteria and had a Mini-SPIN score of 8 or greater , because this improves the accuracy of social anxiety disorder diagnoses ( 37 ) . They based a diagnosis of panic disorder on answering yes to all 5 questions on the PHQ panic module , a threshold that reflects DSM-IV criteria and has been vali date d in both clinical ( 25 ) and population -based ( 38 ) sample s. Statistical Analysis We estimated sample size with respect to sensitivity of the GAD-7 scale for diagnosing the target disease ( generalized anxiety disorder ) . We needed 60 participants with generalized anxiety disorder to ensure that the total width of the 95 % CI around a sensitivity proportion of 0.80 was no greater than 0.20 . Given that the estimated prevalence of generalized anxiety disorder in the primary care population was 6 % ( 18 ) , we needed a total of 1000 unselected primary care patients to have approximately 60 patients with generalized anxiety disorder . We determined the prevalence of each of the 4 anxiety disorders and compared them in patient demographic characteristics , functional status , psychiatric comorbidity , disability days , and physician visits . Consistent with previous work ( 1 , 26 , 29 , 39 ) , we replaced missing values in a scale with the mean value of the remaining items if 25 % or fewer items were missing . If more than 25 % of items were missing , the sum score was not computed and was counted as missing . The amount of missing data for any individual variable or scale score was very low ( < 1 % ) . The 15 sites did not differ in missing data . In addition to descriptive statistics , we used analysis of covariance to examine associations among each anxiety disorder and the 6 SF-20 functional status scales , self-reported disability days , and physician visitscontrolling for demographic variables ( sex , age , race , and educational level ) and study site . We ran similar models to examine the effect of the number of anxiety disorders . In all models , patients with no anxiety disorder were the reference group . We adjusted pairwise statistical comparisons by using the Bonferroni correction . Because some dependent variables displayed a skewed ( but unimodal ) distribution , we also reran the models using the rank transformation of the dependent variables . We examined the operating characteristics ( sensitivity , specificity , and positive likelihood ratio ) for a range of cutoff scores of the GAD-7 and GAD-2 for each anxiety disorder . We conducted receiver-operating characteristic curve analyses to determine the area under the curve ( AUC ) for each anxiety disorder . We calculated AUCs and performed statistical comparisons ( GAD-7 vs. OBJECTIVE The objective of this study was to assess whether individually tailored psychotherapy for patients with functional neurological symptoms is associated with improvements in patient-centered measures of emotional well-being , quality of life , as well as somatic symptoms and whether this treatment modality is likely to be cost-effective . METHODS We conducted an uncontrolled prospect i ve pilot study of consecutive patients with functional symptoms referred from neurology outpatient clinics to a single psychotherapist using vali date d question naires [ Clinical Outcomes in Routine Evaluation Outcome Measure ( CORE-OM ) , Short Function (SF)-36 Health Survey , and Patient Health Question naire (PHQ)-15 ] . Patients had a median of 6 treatment sessions ( range=1 - 24 ) . Ninety-one patients completed question naires at referral , 63 did at the end of treatment , and 34 did at follow-up after 6 months . Significant improvements were seen on all measures and were maintained at follow-up ( CORE-OM , P=.003 ; SF-36 , P<.001 ; PHQ-15 , P=.001 ) . Significance was not lost in an intention-to-treat analysis . Of all the patients , 49.2 % improved by at least 1 S.D. in at least one of the measures . The number of patients needed to be treated to see an improvement of at least 1 S.D. in one of the three outcome measures was 2 ; that in two measures , 3.9 ; and that in all measures , 7 . The mean cost of the intervention was pound231 ; the cost per quality -adjusted life year was estimated as pound5,328 . RESULTS Psychotherapy was associated with significant improvements in patient-centered measures , which seemed to be achieved at a comparatively low cost . CONCLUSIONS The results indicate that psychotherapy may be a cost-effective intervention for patients presenting with functional neurological symptoms . The findings warrant further assessment of this treatment with a r and omized and controlled trial OBJECTIVE Pain and depression are two of the most prevalent and treatable cancer-related symptoms , each present in at least 20 - 30 % of oncology patients . Both symptoms are frequently either unrecognized or undertreated , however . This article describes a telecare management intervention delivered by a nurse-psychiatrist team that is design ed to improve recognition and treatment of pain and depression . The enrolled sample is also described . METHODS The Indiana Cancer Pain and Depression study is a National Cancer Institute-sponsored r and omized clinical trial . Four hundred five patients with cancer-related pain and /or clinical ly significant depression from 16 urban or rural oncology practice s throughout Indiana have been enrolled and r and omized to either the intervention group or to a usual-care control group . Intervention patients receive central ized telecare management coupled with automated home-based symptom monitoring . Outcomes will be assessed at 1 , 3 , 6 and 12 months by research assistants blinded to treatment arms . RESULTS Of 4465 patients screened , 2185 ( 49 % ) endorsed symptoms of pain or depression . Of screen-positive patients , about one-third were ineligible ( most commonly due to pain or depression not meeting severity thresholds or to pain that is not related to cancer ) . Of the 405 patients enrolled , 32 % have depression only , 24 % have pain only and 44 % have both depression and pain . At baseline , participants reported an average of 16.8 days out of the past 4 weeks during which they were confined to bed or had to reduce their usual activities by > or = 50 % due to pain or depression . Also , 176 ( 44 % ) reported being unable to work due to health reasons . CONCLUSIONS When completed , the Indiana Cancer Pain and Depression trial will test whether central ized telecare management coupled with automated home-based symptom monitoring improves outcomes in cancer patients with depression and /or pain . Findings will be important for both oncologists and mental health clinicians confronted with oncology patients ' depression or pain OBJECTIVE To examine how the type and number of physical symptoms reported by primary care patients are related to psychiatric disorders and functional impairment . DESIGN Outpatient mental health survey . SETTING Four primary care clinics . PATIENTS One thous and adult clinic patients , of whom 631 were selected r and omly or consecutively and 369 by convenience . MAIN OUTCOME MEASURES Psychiatric disorders as determined by the Primary Care Evaluation of Mental Disorders procedure ; the presence or absence of 15 common physical symptoms and whether symptoms were somatoform ( ie , lacked an adequate physical explanation ) ; and functional status as determined by the Medical Outcomes Study Short-form General Health Survey . RESULTS Each of the 15 common symptoms was frequently somatoform ( range , 16 % to 33 % ) . The presence of any physical symptom increased the likelihood of a diagnosis of a mood or anxiety disorder by at least twofold to three-fold , and somatoform symptoms had a particularly strong association with psychiatric disorders . The likelihood of a psychiatric disorder increased dramatically with increasing numbers of physical symptoms . The prevalence of a mood disorder in patients with 0 to 1 , 2 to 3 , 4 to 5 , 6 to 8 , and 9 or more symptoms was 2 % , 12 % , 23 % , 44 % , and 60 % , respectively , and the prevalence of an anxiety disorder was 1 % , 7 % , 13 % , 30 % , and 48 % , respectively . Finally , each physical symptom was associated with significant functional impairment ; indeed , the number of physical symptoms was a powerful correlate of functional status . CONCLUSIONS The number of physical symptoms is highly predictive for psychiatric disorders and functional impairment . Multiple or unexplained symptoms may signify a potentially treatable mood or anxiety disorder Background : Somatizing patients have maladaptive and increased rates of medical care utilization . If there were a way of routinely identifying such patients , one that did not require intensive , case-by-case review , they could be targeted for specific interventions to improve their use of medical care . Objective : We sought to identify patterns of medical care utilization that would distinguish somatizing and nonsomatizing medical out patients with acceptable sensitivity and specificity . Design : Subjects completed question naires assessing somatization and sociodemographic characteristics . Their medical care utilization was obtained for the 12 months preceding the index visit . We then used multivariable logistic regression and recursive partitioning to identify patients with a provisional diagnosis of somatoform disorder . These exploratory models used various patterns of medical care utilization and sociodemographic characteristics as the independent variables . Subjects : We studied consecutive adults attending 2 primary care practice s on r and omly chosen days . Measures : The provisional diagnosis of a somatoform disorder was assessed with a 15-item self-report question naire . The number of primary care visits , specialty visits , mental health visits , emergency visits , and inpatient and outpatient costs were obtained for the 12 months preceding the index visit from our hospital 's automated medical records , which also provided a rating of aggregate medical morbidity . Self-reported utilization outside our hospital system was obtained from a sub sample of patients . Results : Complete data were obtained on 1440 patients . Somatizing patients had more specialty care than primary care visits , higher outpatient than inpatient costs , and more emergency visits than nonsomatizing patients . A regression model containing 7 measures of utilization and 4 sociodemographic characteristics distinguished somatizing and nonsomatizing patients with a c-statistic = 0.73 . Recursive partitioning identified 10 terminal nodes with a very high specificity ( 99 % ) but a very low sensitivity ( 15 % ) . Conclusions : We identified 7 discrete patterns of medical care utilization that distinguished somatizing and nonsomatizing patients . However , they did so with only modest specificity and sensitivity . This algorithm might be used effectively as the first step in a 2-step screening procedure whose second step would entail more intensive screening or individual , case-by-case review to identify somatizing patients in primary care practice OBJECTIVE The main objectives of this study were to explore the preliminary outcomes and assess the feasibility and acceptability of a collaborative care intervention design ed to improve treatment and outcomes of depression among youth seen in primary care setting s. METHODS We conducted a pilot intervention study at three clinics in a university affiliated primary care clinic network . The intervention model was design ed to support the provision of depression treatment by primary care providers using methods adapted from the IMPACT study developed for the improvement of depression among older adults . Specific components include the provision of regular case management by a nurse depression care manager ( DCM ) , enhanced patient and parent education about depression and its treatment , encouragement of patient self-management with a choice of starting medications or therapy or both , and oversight of the DCM by a mental health specialist . Study participants were assessed regularly by the DCM for 6 months and completed written self-report assessment s at baseline , 3 , and 6 months after starting the intervention . RESULTS 40 youth ( 12 - 18 years ) with major and minor depression enrolled in the intervention . Study participants were predominantly female ( 90 % ) . The baseline Patient Health Question naire ( PHQ-9 ) score was 14.2 ( SD=4.5 ) . Patients were similarly divided among initiating medications ( n=12 ) , therapy ( n=15 ) , or combination therapy ( n=8 ) . Five patients withdrew prior to initiating treatment . The mean number of in person and telephone contacts with the DCM was 9 ( range=5 to 17 ) . Eighty-seven percent of youth completed the 6-month intervention . At 6 month follow-up , 74 % of youth had a 50 % or more reduction in depressive symptoms as measured by the PHQ-9 . Parents , youth and physicians indicated high levels of satisfaction with the intervention on written surveys and in qualitative exit interviews . CONCLUSION The collaborative care model is feasible and highly acceptable to adolescents and parents as demonstrated both by self-report and by engagement in the intervention . It is also associated with improved depressive outcomes at similar levels to adult interventions . Future studies should evaluate these models in a r and omized controlled trial OBJECTIVE This study evaluates the two-item Patient Health Question naire ( PHQ-2 ) as a measure for diagnosing and monitoring depression . METHODS We assessed construct validity in a cross-sectional sample of 1619 medical out patients ( mean age 43+/-14 years , 64 % female ) by comparing the PHQ-2 to four longer self-report question naires . Criterion validity was established in a sub sample of 520 participants with reference to the Structured Clinical Interview for DSM-IV ( SCID ) . Sensitivity to change was investigated in a prospect i ve study of 167 patients who completed the SCID both at baseline and the 1-year follow-up . RESULTS With reference to the SCID , the PHQ-2 had a sensitivity of 87 % and a specificity of 78 % for major depressive disorder and a sensitivity of 79 % and a specificity of 86 % for any depressive disorder . Its diagnostic performance was comparable with that of longer depression scales . PHQ-2 change scores accurately reflected improved , unchanged , and deteriorated depression outcomes . CONCLUSION The PHQ-2 performed favorably with respect to a st and ard diagnostic interview , as well as established depression scales and proved sensitive to change . Thus , the PHQ-2 appears promising as a brief multi purpose measure for detecting depression , grading its severity , and monitoring outcomes over time OBJECTIVE This study examined the unadjusted and adjusted prevalence estimates of depression and anxiety at the state level and examined the odds ratios of depression and anxiety for selected risk behaviors , obesity , and chronic diseases . METHODS The 2006 Behavioral Risk Factor Surveillance Survey , a r and om-digit-dialed telephone survey , collected depression and anxiety data from 217,379 participants in 38 states , the District of Columbia , Puerto Rico , and the U.S. Virgin Isl and s. Current depressive symptoms were assessed with the st and ardized and vali date d eight-item Patient Health Question naire , and lifetime diagnosis of depression and anxiety was assessed by two additional questions ( one question for each diagnosis ) . RESULTS The overall prevalence of current depressive symptoms was 8.7 % ( range by state and territory , 5.3%-13.7 % ) ; of a lifetime diagnosis of depression , 15.7 % ( range , 6.8%-21.3 % ) ; and of a lifetime diagnosis of anxiety , 11.3 % ( range , 5.4%-17.2 % ) . After sociodemographic characteristics , adverse health behaviors , and chronic illnesses were adjusted for , cardiovascular disease , diabetes , asthma , smoking , and obesity were all significantly associated with current depressive symptoms , a lifetime diagnosis of anxiety , and a lifetime diagnosis of depression . Physically inactive adults were significantly more likely than those who were physically active to have current depressive symptoms or a lifetime diagnosis of depression , whereas those who drank heavily were significantly more likely than those who did not to have current depressive symptoms or a lifetime diagnosis of anxiety . CONCLUSIONS Depression and anxiety were strongly associated with common chronic medical disorders and adverse health behaviors . Examination of mental health should therefore be an integral component of overall health care Objective To test the validity and reliability of the Patient Health Question naire-9 ( PHQ-9 ) for diagnosing major depressive disorder ( MDD ) among persons with traumatic brain injury ( TBI ) . Design Prospect i ve cohort study . Setting Level I trauma center . Participants 135 adults within 1 year of complicated mild , moderate , or severe TBI . Main Outcome Measures PHQ-9 Depression Scale , Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( SCID ) . Results Using a screening criterion of at least 5 PHQ-9 symptoms present at least several days over the last 2 weeks ( with one being depressed mood or anhedonia ) maximizes sensitivity ( 0.93 ) and specificity ( 0.89 ) while providing a positive predictive value of 0.63 and a negative predictive value of 0.99 when compared to SCID diagnosis of MDD . Pearson 's correlation between the PHQ-9 scores and other depression measures was 0.90 with the Hopkins Symptom Checklist depression subscale and 0.78 with the Hamilton Rating Scale for Depression . Test-retest reliability of the PHQ-9 was r = 0.76 and κ = 0.46 when using the optimal screening method . Conclusions The PHQ-9 is a valid and reliable screening tool for detecting MDD in persons with TBI Almost 20 years ago , Barsky ( 1 ) wrote of hidden reasons why patients seek medical care , and he suggested that patient dissatisfaction should trigger exploration for unmet expectations . Subsequent research has shown that patient expectations , distinct from requests ( 2 ) , are ubiquitous . Broad categories include expectations of information , support , and medical diagnosis or treatment ( 3 , 4 ) . Unfortunately , physicians often undervalue or do not recognize patient expectations ( 5 - 7 ) , and expectations are therefore often unmet ( 8 - 14 ) . Unmet expectations have been associated with decreased patient satisfaction ( 8 , 15 - 21 ) , no adherence ( 15 , 22 - 24 ) , and possibly worse health-related outcomes ( 18 , 25 ) . Our goal was to determine the frequency of symptom-related patient concerns and expectations and to assess the relationship between expectations and patient-centered outcomes . Methods Adults presenting to the general medicine walk-in clinic at Walter Reed Army Medical Center , Washington , D.C. , with a chief complaint of a physical symptom were eligible to participate . The demographic characteristics , medical and psychiatric comorbid conditions , and satisfaction with care of patients seen in a military general medicine clinic are similar to those seen in civilian setting s ( 26 , 27 ) . These protocol s were approved by our institutional human use committee . Previsit Patient Question naire Immediately before seeing a physician , all patients completed a question naire on their presenting symptom ( What problem brings you to the clinic today ? ) , symptom severity ( ranked from 0 to 10 on a visual analogue scale ) , symptom duration ( in days ) , previous visits for the symptom ( yes or no ) , worry about serious illness ( yes or no ) , stress in the previous week ( yes or no ) , and presence of common symptom-related expectations . The expectations included expectations of a diagnosis ( an explanation of the symptom 's cause ) , prognostic information ( an estimate of how long the symptom was likely to last ) , a prescription , a diagnostic test , a referral to another clinic , or another physician action ( 8 , 13 ) . In addition , all patients completed the Medical Outcomes Study Short Form-6 , a six-item scale that measures functional status in six domains : general health , role function , physical function , social function , emotional health , and physical pain ( 28 ) . Patients were also evaluated for depressive and anxiety disorders by using the Primary Care Evaluation of Mental Disorders ( PRIME-MD ) ( 29 ) . Postvisit Patient Question naire Immediately after the visit , patients completed the Medical Outcomes Study nine-item satisfaction survey ( 30 ) , which asks about overall satisfaction and eight domains of satisfaction . Additional questions assessed residual worry about serious illness and unmet expectations with respect to a diagnosis , prognostic information , a prescription , a diagnostic test , or a referral . Patients were invited to list any other unmet expectations . Two-Week Patient Question naire Two weeks after the visit , patients were mailed a question naire that assessed symptom outcome and severity , residual worry about serious illness , unmet expectations , functional status ( Medical Outcomes Study Short Form-6 ) , and a single question on satisfaction : Overall , how do you feel about the care you received for this problem from your doctor ? Patients were also asked whether they had had or had anticipated having another physician visit for the original symptom and whether the symptom had lasted longer than expected . Physician Variables After each visit , physicians completed the 10-item Difficult Doctor Patient Relationship Question naire ( 31 ) to assess clinician-perceived difficulty of the encounter . This question naire was previously shown to be reliable , with scores greater than 30 points ( on a scale of 10 to 60 points ) indicating a difficult encounter ( 32 ) . Physicians also indicated whether the symptom had led them to order a prescription , diagnostic test , or referral and whether they had told the patient what the problem was and how long it would probably last . Statistical Analysis Our primary analysis assessed the presence of unmet expectations immediately after the visit and 2 weeks after the visit in relation to other variables , using the chi-square test or the Student t-test . The McNemar test was used to compare the proportion of patients who had an unmet expectation immediately after the visit with the proportion of patients who had an unmet expectation at 2 weeks . To assess functional status , overall scores were created by summing scores for each of the individual domains . Logistic regression techniques were used to determine independent correlates of unmet expectations and satisfaction . Unmet expectations were dichotomized into any unmet expectation or no unmet expectation ; overall satisfaction was dichotomized into fully satisfied or less than fully satisfied . Overall satisfaction was used at both time points for two reasons . First , each of the eight domains of satisfaction of the Medical Outcomes Study survey correlated strongly with overall satisfaction ( r > 0.85 ) . Second , we thought that at 2 weeks , patients would recall overall satisfaction more accurately than they would recall specific aspects of the encounter . Data were collected as part of two clinical trials in which previsit information on patients ' symptom-related expectations and mental disorders was given to clinicians . Both trials were done in the same clinic , had the same inclusion criteria ( walk-in patients presenting with a physical symptom ) , and included the same survey instruments . The first study , a prepost trial involving 500 patients , was conducted from November 1994 to January 1996 ( 33 ) . During the intervention period , physicians were given previsit information about their patients ' worry over serious illness , expectations of care , and mental disorders . The second study , a r and omized trial involving 250 patients , was done from August to September 1998 . Patients were r and omly assigned to one of three groups . One group 's clinicians were given no information , the second group 's clinicians were given previsit information about worry over serious illness and expectations , and the third group 's clinicians received information about mental disorders . The two cohorts were similar in terms of patient sex , race , educational status , worry over serious illness , symptom duration , symptom type or severity , number of previsit expectations , functional status , recent stress , prevalence of mental disorders , satisfaction , and 2-week improvement rates . Patients in the first cohort were slightly older than those in the second ( 55 years vs. 51 years ; P=0.007 ) . Because the two cohorts were similar in most variables and visited the same clinic , they were combined into one group for purpose s of our analysis . Although no differences were seen in any outcome measured in the second trial , the prepost trial modestly reduced unmet expectations and patient difficulty ( 33 ) . We explored for potential confounding of our outcomes by this intervention ; because we found none , we report all data unadjusted . All analyses were done by using Stata 6.0 ( Stata Corp. , College Station , Texas ) . Results Baseline Data Table 1 presents the baseline characteristics of the study sample . The 750 participating patients averaged 55 years of age ; 52 % were women , 49 % were white , and 46 % were African American . Most patients ( 93 % ) were seeing the examining physician for the first time . Thirty percent of patients had a depressive or anxiety disorder . Patients presented with numerous problems , which we collapsed into 15 broad categories . One hundred forty-three patients ( 19 % ) answered the question What problem brings you to the clinic ? by stating that they had more than one physical symptom , 97 ( 13 % ) noted two symptoms , 14 ( 2 % ) had three symptoms , and 3 ( 0.4 % ) listed four symptoms . The most common type of symptom was pain ( 53 % ) , and the second most common was symptoms suggestive of an upper respiratory tract infection ( congestion or cough ) , present in 21 % . In addition to listing their presenting symptoms , patients were asked whether they had been often bothered by 15 common symptoms on the PRIME-MD . Patients had had a mean ( SD ) of 4 2.8 of these symptoms during the past month ( median , 4 ; range , 0 to 14 ) . The median duration of the presenting physical symptom was 14 days ( range , 12 hours to 13 years ) . Sixty-three percent of patients were worried that their symptom might represent a serious illness . Table 1 . Characteristics of the Study Sample Nearly all patients ( 98 % ) reported at least one previsit expectation ( Table 2 ) . Eighty-one percent hoped for a diagnosis ( an explanation of the symptom 's cause ) , and 63 % desired prognostic information ( an estimate of how long the symptom would last ) . Sixty-six percent hoped for a prescription , 54 % a diagnostic test , 45 % a subspecialty referral , and 7 % an excuse from work . The 250 patients in the r and omized trial were also asked about expectations for counseling or referral for specific issues , but these expectations were held by only small proportions of patients . The specific issues included tobacco use ( 0.43 % ) , nutrition ( 1.7 % ) , alcohol use ( 0.43 % ) , obesity ( 1.7 % ) , exercise ( 1.3 % ) , cancer screening ( 0.9 % ) , cholesterol levels ( 1.3 % ) , sexual function ( 0.43 % ) , stress management ( 2.2 % ) , and domestic violence ( 0 % ) . Table 2 . Prevalence of Symptom-Related Expectations Most patients had more than one expectation for the visit , and the mean number of expectations was 3 1.3 ( Figure ) . Patients who desired a diagnosis were more likely to want prognostic information ( relative risk [ RR ] , 1.6 [ 95 % CI , 1.5 to 1.8 ] ) , but neither of these expectations clustered with desires for a prescription , test , or referral . In addition , no evidence was seen of clustering of desires for prescriptions , referrals , or diagnostic testing . Neither the type nor the number of previsit expectations was associated with demographic characteristics ; This is the first study that investigates the responsiveness of the Patient Health Question naire-9 ( PHQ-9 ) , a st and ard 9-item self-report depression scale , to antidepressant medication . Authors analyzed data from 1,788 depressed out patients ( 66.8 % women ; mean age , 50.3 years ) , participating in a prospect i ve , open-label , non-interventional , observational study of sertraline . On the 0 - 27-point PHQ-9 scale , the total sample gained 10.3 points at 12 weeks , corresponding to a st and ardized effect size of -1.85 . With reference to two independent criterion st and ards , the PHQ-9 change scores were considerably greater in therapy responders than in nonresponders . The PHQ-9 was equally responsive in men and women . Therefore , the PHQ-9 qualifies as a practical tool for gauging response to pharmacological treatment in depressed patients OBJECTIVE Only half of patients with depressive disorder are diagnosed by their family physicians . Screening in high-risk groups might reduce this hidden morbidity . This study aims to determine the accuracy of the Patient Health Question naire-9 ( PHQ-9 ) in ( a ) screening for depressive disorder , ( b ) diagnosing depressive disorder and ( c ) measuring the severity of depressive disorder in groups that are at high risk for depressive disorder . METHOD We compared the performance of the PHQ-9 as a screening instrument and as a diagnostic instrument to that of the Structured Clinical Interview for DSM-IV Axis I Disorders ( SCID-I ) interview , which we used as reference st and ard . Three high-risk groups of patients were selected : ( a ) frequent attenders , ( b ) patients with mental health problems and ( c ) patients with unexplained complaints . Patients completed the PHQ-9 . Next , patients who were at risk for depression ( based on PHQ scores ) and a r and om sample of 20 % of patients who were not at risk were selected for a second PHQ-9 and the reference st and ard ( SCID-I ) . We assessed the adequacy of the PHQ-9 as a tool for severity measurement by comparing PHQ-9 scores with scores on the 17-item Hamilton Depression Rating Scale ( HDRS-17 ) in patients diagnosed with a depressive disorder . RESULTS Among 440 patients , both PHQ-9 and SCID-I were analyzed . The test characteristics for screening were sensitivity=0.93 and specificity=0.85 ; those for diagnosing were sensitivity=0.68 and specificity=0.95 . The positive likelihood ratio for diagnosing was 14.2 . The HDRS-17 was administered in 49 patients with depressive disorder . The Pearson correlation coefficient of the PHQ-9 to the HDRS-17 was r=.52 ( P<.01 ) . CONCLUSION The PHQ-9 performs well as a screening instrument , but in diagnosing depressive disorder , a formal diagnostic process following the PHQ-9 remains imperative . The PHQ-9 does not seem adequate for measuring severity |
2,362 | 29,208,190 | Exposure to information on improving injecting techniques did not encourage riskier injecting practice s or injecting frequency , and benefits were reported among attendees .
The intervention has the potential to positively influence BBV prevention .
FUTURE WORK The intervention did not meet the complex needs of some PWID , more tailoring may be needed to reach PWID who are more frequent injectors , who are homeless and female .
LIMITATIONS Intervention delivery proved more feasible in London than other locations .
Non-attendance at the York trial site substantially influenced the results . | BACKGROUND Opioid substitution therapy and needle exchanges have reduced blood-borne viruses ( BBVs ) among people who inject drugs ( PWID ) .
Some PWID continue to share injecting equipment .
OBJECTIVES To develop an evidence -based psychosocial intervention to reduce BBV risk behaviours and increase transmission knowledge among PWID , and conduct a feasibility trial among PWID comparing the intervention with a control . | Contingency management ( CM ) rapidly reduces cocaine use , but its effects subside after treatment . Cognitive-behavioral therapy ( CBT ) produces reductions months after treatment . Combined , the 2 might be complementary . One hundred ninety-three cocaine-using methadone-maintained out patients were r and omly assigned to 12 weeks of group therapy ( CBT or a control condition ) and voucher availability ( CM contingent on cocaine-negative urine or noncontingent ) . Follow-ups occurred 3 , 6 , and 12 months posttreatment . Primary outcome was cocaine-negative urine ( urinalysis 3 times/week during treatment and once at each follow-up ) . During treatment , initial effects of CM were dampened by CBT . Posttreatment , there were signs of additive benefits , significant in 3- versus 12-month contrasts . Former CBT participants were also more likely to acknowledge cocaine use and its effects and to report employment BACKGROUND Injection drug use directly or indirectly accounts for nearly half the annual human immunodeficiency virus ( HIV ) infections in the United States . Prospect i ve studies that investigate both sexual and parenteral HIV risks among injection drug users ( IDUs ) are needed . We studied factors for HIV seroconversion among male and female IDUs in Baltimore , Md. METHODS The HIV-negative IDUs ( 1447 male and 427 female ) were recruited into a prospect i ve study from 1988 to 1989 or in 1994 . Participants underwent semiannual HIV tests and surveys through December 1998 . Poisson regression was used to identify risk factors for HIV seroconversion , stratified by sex . Behaviors were treated as time-dependent covariates that varied at each semiannual period . RESULTS Subjects were primarily African American ( 91 % ) , and median age at enrollment was 35 years . Incidence of HIV was 3.14 per 100 person years ( 95 % confidence interval , 2.78 - 3.53 ) and did not significantly differ by sex . Younger age independently predicted HIV seroconversion for both men and women . Among men , factors that independently predicted HIV seroconversion were the following : less than a high school education , recent needle sharing with multiple partners , daily injection , and shooting-gallery attendance . The incidence of HIV was double for men recently engaging in homosexual activity and cocaine injection . Among women , the incidence of HIV was more than double for those recently reporting sexually transmitted diseases . CONCLUSIONS The incidence of HIV remained high among IDUs in Baltimore over the past decade . Risk factors for HIV seroconversion differed markedly by sex . Predominant risks among men included needle sharing and homosexual activity ; among women , factors consistent with high-risk heterosexual activity were more significant than drug-related risks . Human immunodeficiency virus interventions aim ed at IDUs should be sex-specific and incorporate sexual risks A r and omized trial was conducted to test the effectiveness of couple-based HIV counseling and testing ( CB-HIV-CT ) and women-only relationship-focused HIV counseling and testing ( WRF-HIV-CT ) in reducing HIV risk compared to the National Institute on Drug Abuse HIV-CT st and ard intervention . Substance using HIV-negative women and their primary heterosexual partner ( N = 330 couples ) were r and omized to 1 of the 3 interventions . Follow-up assessment s measuring HIV risk behaviors and other relevant variables were conducted at 3- and 9-months postintervention . Repeated measures generalized linear mixed model analysis was used to assess treatment effects . A significant reduction in HIV risk was observed over the 9-month assessment in the CB-HIV-CT group compared to that of the control group ( b = −0.51 , t[527 ] = −3.20 , P = 0.002 ) and compared to that of the WRF-HIV-CT group ( b = −0.34 , t[527 ] = −2.07 , P = 0.04 ) , but no significant difference was observed between WRF-HIV-CT and controls ( b = −0.17 , t[527 ] = −1.09 , P = 0.28 ) . A brief couple-based HIV counseling and testing intervention design ed to address both drug-related and sexual risk behaviors among substance using women and their primary male partners was shown to be more effective at reducing overall HIV risk compared to a st and ard HIV-CT intervention in an urban setting Background : There is a lack of effective behavioral interventions for HIV-positive injection drug users ( IDUs ) . We sought to evaluate the efficacy of an intervention to reduce sexual and injection transmission risk behaviors and to increase utilization of medical care and adherence to HIV medications among this population . Methods : HIV-positive IDUs ( n = 966 ) recruited in 4 US cities were r and omly assigned to a 10-session peer mentoring intervention or to an 8-session video discussion intervention ( control condition ) . Participants completed audio computer-assisted self-interviews and had their blood drawn to measure CD4 cell count and viral load at baseline and at 3-month ( no blood ) , 6-month , and 12-month follow-ups . Results : Overall retention rates for r and omized participants were 87 % , 83 % , and 85 % at 3 , 6 , and 12 months , respectively . Participants in both conditions reported significant reductions from baseline in injection and sexual transmission risk behaviors , but there were no significant differences between conditions . Participants in both conditions reported no change in medical care and adherence , and there were no significant differences between conditions . Conclusions : Both interventions led to decreases in risk behaviors but no changes in medical outcomes . The characteristics of the trial that may have contributed to these results are examined , and directions for future research are identified OBJECTIVES We evaluated the efficacy of a peer-mentoring behavioral intervention design ed to reduce risky distributive injection practice s ( e.g. , syringe lending , unsafe drug preparation ) among injection drug users with hepatitis C virus ( HCV ) infection . METHODS A r and omized trial with a time-equivalent attention-control group was conducted among 418 HCV-positive injection drug users aged 18 to 35 years in 3 US cities . Participants reported their injection-related behaviors at baseline and at 3- and 6-month follow-ups . RESULTS Compared with the control group , intervention-group participants were less likely to report distributive risk behaviors at 3 months ( odds ratio [OR]=0.46 ; 95 % confidence interval [CI]=0.27 , 0.79 ) and 6 months ( OR=0.51 ; 95 % CI=0.31 , 0.83 ) , a 26 % relative risk reduction , but were no more likely to cite their HCV-positive status as a reason for refraining from syringe lending . Effects were strongest among intervention-group participants who had known their HCV-positive status for at least 6 months . Peer mentoring and self-efficacy were significantly increased among intervention-group participants , and intervention effects were mediated through improved self-efficacy . CONCLUSIONS This behavioral intervention reduced unsafe injection practice s that may propagate HCV among injection drug users Background We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs ( FSW-IDUs ) in Tijuana and Ciudad Juarez , Mexico during 2008–2010 , when harm reduction coverage was exp and ing rapidly in Tijuana , but less so in Juarez . Methods FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a r and omized factorial trial comparing four brief , single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use , and an injection risk intervention to reduce sharing of needles/injection paraphernalia . Women underwent quarterly interviews and testing for HIV , syphilis , gonorrhea , Chlamydia and Trichomonas , blinding interviewers and assessors to assignment . Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency . Findings Of 584 initially HIV-negative FSW-IDUs , retention was ≥90 % . After 12 months , HIV/STI incidence decreased > 50 % in the interactive vs. didactic sex intervention ( Tijuana : AdjRR:0.38,95 % CI:0.16–0.89 ; Juarez : AdjRR:0.44,95 % CI:0.19–0.99 ) . In Juarez , women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85 % vs. 71 % , respectively ( p = 0.04 ) ; in Tijuana , receptive needle sharing declined by 95 % , but was similar in active versus didactic groups . Tijuana women reported significant increases in access to syringes and condoms , but Juarez women did not . Interpretation After 12 months in both cities , the interactive sexual risk intervention significantly reduced HIV/STI incidence . Exp and ing free access to sterile syringes coupled with brief , didactic education on safer injection was necessary and sufficient for achieving robust , sustained injection risk reductions in Tijuana . In the absence of exp and ing syringe access in Juarez , the injection risk intervention achieved significant , albeit more modest reductions , suggesting that community-level interventions incorporating harm reduction are more powerful than individual-level interventions . Trial Registration clinical trials.gov Active injection drug users ( IDUs ) who are also hazardous alcohol users are at particularly high risk for HIV transmission due to sharing of injection equipment . We recruited AUDIT-positive injectors from the Providence , RI needle exchange program for a r and omized clinical trial testing the effect of a brief motivational intervention ( MI ) on frequency of injection-related HIV risk behavior ( IRRB ) . HIV drug risk behavior was measured as the number of days on which subjects reported sharing works using the 30-day Timeline Followback Method . Overall , 109 subjects reported a mean reduction of IRRB days of 9.1 days from baseline to 6-month follow-up ( p < .001 ) . When compared to controls , there was a trend in reduction of IRRB days to zero at follow-up for MI subject ( OR = 2.1 ; 95 % CI = 0.9 - 4.5 ) , and strongly significant reductions in IRRB days across a range of alternative improvement thresholds . Results from this study demonstrate that MI reduces drug-related HIV risk behaviors among active IDUs . As a brief intervention , MI may be a useful adjunct to existing services intended to reduce harm AIM Contingency management ( CM ) is efficacious in reducing drug use . This study examined whether CM also reduces human immunodeficiency virus ( HIV ) risk behaviors and if these effects are mediated by longest duration of abstinence achieved during treatment . DESIGN Data were analyzed from a subset of participants in a combined data set of three published r and omized controlled trials of CM treatments . SETTING A community-based methadone maintenance clinic . PARTICIPANTS One-hundred and sixty-five cocaine-abusing methadone maintenance patients . INTERVENTION Participants received either st and ard methadone treatment or st and ard methadone treatment with CM for 3 months . MEASUREMENTS The HIV Risk Behavior Scale ( HRBS ) was administered prior to r and omization to a study condition and 3 months after the study treatments ended . The primary objective indicator of drug use was longest duration of cocaine and opioid abstinence achieved during treatment . FINDINGS Relative to those assigned to st and ard care , participants receiving CM significantly decreased overall HIV risk behaviors and injection drug use risk behaviors . CM participants also achieved longer duration s of consecutive cocaine and opioid abstinence during treatment . Duration of abstinence achieved mediated the relationship between treatment condition and HRBS difference scores . CONCLUSIONS These results suggest that CM treatment reduces HIV drug use risk behaviors in cocaine-abusing methadone maintenance patients The authors conducted a preliminary study of the 4-session Holistic Health for HIV ( 3H+ ) , which was adapted from a 12-session evidence -based risk reduction and antiretroviral adherence intervention . Improvements were found in the behavioral skills required to properly adhere to HIV medication regimens . Enhancements were found in all measured aspects of sex-risk reduction outcomes , including HIV knowledge , motivation to reduce sex-risk behavior , behavioral skills related to engaging in reduced sexual risk , and reduced risk behavior . Improvements in drug use outcomes included enhancements in risk reduction skills as well as reduced heroin and cocaine use . Intervention effects also showed durability from post-intervention to the follow-up assessment point . Females responded particularly well in terms of improvements in risk reduction skills and risk behavior . This study suggests that an evidence -based behavioral intervention may be successfully adapted for use in community-based clinical setting s where HIV-infected drug users can be more efficiently reached Injection drug use is a leading transmission route of HIV and STDs , and disease prevention among drug users is an important public health concern . This study assesses cost-effectiveness of behavioral interventions for reducing HIV and STDs infections among injection drug-using women . Cost-effectiveness analysis was conducted from societal and provider perspectives for r and omized trial data and Bernoullian model estimates of infections averted for three increasingly intensive interventions : ( 1 ) NIDA ’s st and ard intervention ( SI ) ; ( 2 ) SI plus a well woman exam ( WWE ) ; and ( 3 ) SI , WWE , plus four educational sessions ( 4ES ) . Trial results indicate that 4ES was cost-effective relative to WWE , which was dominated by SI , for most diseases . Model estimates , however , suggest that WWE was cost-effective relative to SI and dominated 4ES for all diseases . Trial and model results agree that WWE is cost-effective relative to SI per hepatitis C infection averted ( $ 109 308 for in trial , $ 6 016 in model ) and per gonorrhea infection averted ( $ 9 461 in trial , $ 14 044 in model ) . In sensitivity analysis , trial results are sensitive to 5 % change in WWE effectiveness relative to SI for hepatitis C and HIV . In the model , WWE remained cost-effective or cost-saving relative to SI for HIV prevention across a range of assumptions . WWE is cost-effective relative to SI for preventing hepatitis C and gonorrhea . WWE may have similar effects as the costlier 4ES BACKGROUND This study estimates the past year prevalence of and factors associated with sex trading ( offering sex for money , drugs or something else ) among 1796 men and women presenting to 342 drug misuse treatment agencies in Engl and , and identifies service development and delivery implication s. METHODS Secondary analysis of baseline data from a prospect i ve cohort was conducted . Short Form-12 measured mental and physical wellbeing , psychiatric diagnoses were self-reported and the circumstances , motivation and readiness tool assessed readiness for/pressure to enter treatment . Logistic regression models determined associations with sex trading separately by sex . Inverse probability population weights were calculated , utilising demographics from the National Drug Treatment Monitoring System and agency specific data collection windows . RESULTS The estimated prevalence rate of sex trading in the past 12 months was 5.1 % ( 15.0 % for women and 2.1 % for men ) . For women , adjusted models identified crack use ( aOR 1.83 , 95 % CI 1.22 - 2.74 , p=0.004 ) , previous treatment ( aOR 3.00 , 95 % CI 1.31 - 6.86 , p=0.010 ) and greater readiness for treatment ( aOR 1.12 , 95 % CI 1.01 - 1.24 , p=0.027 ) as independently associated with sex trading . For men , lower mental wellbeing ( aOR 0.97 , 95 % CI 0.94 - 0.99 , p=0.030 ) was independently associated and marginal effects were identified for syringe sharing ( aOR 2.89 , 95 % CI 0.94 - 8.86 , p=0.064 ) and unprotected sex ( aOR 2.23 , 95 % CI 0.95 - 5.26 , p=0.065 ) . CONCLUSIONS Sex trading among drug misusers is associated with additional health risks and specific treatment needs . Given the scale of the problem it is important that treatment providers have the competencies to adequately address the issue and provide accessible and appropriate services Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES We compared the effects of 2 interventions on alcohol use , use of a new syringe at last injection , and condom use at last sexual encounter in a community sample of injection drug users . METHODS Between 2003 and 2006 , 851 out-of-treatment injection drug users were recruited in Raleigh , NC , and Durham , NC , through street outreach and were r and omly assigned to either a 6-session educational intervention or a 6-session motivational intervention . Intervention effects were examined at 6 and 12 months after enrollment . RESULTS In multiple logistic regression analyses adjusted for baseline alcohol use and HCV status , participants assigned to the motivational intervention were significantly less likely than were participants in the educational intervention to be drinking at the 6-month follow-up ( odds ratio = 0.67 ; 95 % confidence interval = 0.46 , 0.97 ) . There were no significant between-group differences in use of a new syringe at last injection or condom use at last sexual encounter at either follow-up . CONCLUSIONS Reducing alcohol use among persons with HCV may slow disease progression and provide important health benefits . Additional strategies are needed for slowing HCV disease progression until more effective HCV treatments are available This study r and omized 90 HIV-seropositive , methadone-maintained injection drug users ( IDUs ) to an HIV Harm Reduction Program ( HHRP+ ) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project . The treatment phase lasted 6 months , with follow-ups at 6 and 9 months after treatment entry . Patients in both treatments showed reductions in risk behaviors . However , patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment ; at follow-up , they had lower addiction severity scores and were less likely to have engaged in high risk behavior . Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors AIMS Social norms are a key source of influence on health behaviors . This study examined changes in social norms and relationships between HIV injection risk behaviors and social norms among injection drug users ( IDUs ) involved in an experimental intervention . DESIGN R and omized clinical trial . SETTING An HIV Prevention Trials Network study , Philadelphia , USA . PARTICIPANTS IDUs , called indexes , and their social network members , who were drug or sex partners , were recruited for an HIV prevention intervention and followed for up to 30 months ( n = 652 ) . Indexes were r and omized into a peer education intervention or control condition . MEASUREMENTS Outcomes of injection-related HIV risk behaviors ( sharing needles , sharing cookers , sharing cotton , front-/back-loading ) were measured every 6 months and the social norms of these four risk behaviors were assessed every 12 months . FINDINGS There was a statistically significant intervention effect on all four social norms of injection behaviors , with participants in the intervention reporting less risky social norms compared with controls ( changes in mean score : needles , -0.24 , P = 0.007 ; cookers , -0.33 , P = .004 ; cottons , -0.28 , P = .0165 ; front-/back-loading , -0.23 , P = .002 ) . There was also a statistically significant bidirectional association with social norms predicting injection risk behaviors at the next assessment and risk behaviors predicting social norms at the subsequent visit . CONCLUSIONS Through social network interventions it is feasible to change both injection risk behaviors and associated social norms . However , it is critical that social network interventions focus on publically highlighting behavior changes , as changing social norms without awareness of behaviors change may lead to relapse of risk behaviors CONTEXT Despite evidence that methadone maintenance treatment ( MMT ) is effective for opioid dependence , it remains a controversial therapy because of its indefinite provision of a dependence-producing medication . OBJECTIVE To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment , psychosocially enriched 180-day methadone-assisted detoxification . DESIGN R and omized controlled trial conducted from May 1995 to April 1999 . SETTING Research clinic in an established drug treatment service . PATIENTS Of 858 volunteers screened , 179 adults with diagnosed opioid dependence were r and omized into the study ; 154 completed 12 weeks of follow-up . INTERVENTIONS Patients were r and omized to MMT ( n = 91 ) , which required 2 hours of psychosocial therapy per week during the first 6 months ; or detoxification ( n = 88 ) , which required 3 hours of psychosocial therapy per week , 14 education sessions , and 1 hour of cocaine group therapy , if appropriate , for 6 months , and 6 months of ( nonmethadone ) aftercare services . MAIN OUTCOME MEASURES Treatment retention , heroin and cocaine abstinence ( by self-report and monthly urinalysis ) , human immunodeficiency virus ( HIV ) risk behaviors ( Risk of AIDS Behavior scale score ) , and function in 5 problem areas : employment , family , psychiatric , legal , and alcohol use ( Addiction Severity Index ) , compared by intervention group . RESULTS Methadone maintenance therapy result ed in greater treatment retention ( median , 438.5 vs 174.0 days ) and lower heroin use rates than did detoxification . Cocaine use was more closely related to study dropout in detoxification than in MMT . Methadone maintenance therapy result ed in a lower rate of drug-related ( mean [ SD ] at 12 months , 2.17 [ 3.88 ] vs 3.73 [ 6.86 ] ) but not sex-related HIV risk behaviors and in a lower severity score for legal status ( mean [ SD ] at 12 months , 0.05 [ 0.13 ] vs 0.13 [ 0.19 ] ) . There were no differences between groups in employment or family functioning or alcohol use . In both groups , monthly heroin use rates were 50 % or greater , but days of use per month dropped markedly from baseline . CONCLUSIONS Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors . Illicit opioid use continued in both groups , but frequency was reduced . Results do not provide support for diverting re sources from MMT into long-term detoxification Aim To develop and evaluate the comparative effectiveness of behavioural interventions of enhanced prevention counselling ( EPC ) and simple educational counselling ( SEC ) in reducing hepatitis C viral ( HCV ) infection in sero-negative injecting drug users ( IDU ) . Design R and omised controlled trial ( RCT ) of EPC intervention in comparison with simple educational counselling ( SEC ) . Setting SpecialisedDrug services in London and Surrey , United Kingdom . Participants and Measurements Ninety five IDUs were recruited and r and omised to receive EPC ( n = 43 ) or SEC ( n = 52 ) . Subjects were assessed at baseline using the Addiction Severity Index ( ASI ) , the Injecting Risk Question naire ( IRQ ) , and Drug Injecting Confidence Question naire ( DICQ ) . The primary outcome was measured by the rate of sero-conversion at 6 months and 12 months from baseline and by the ASI , IRQ and DICQ at 6 months from baseline . Hepatitis C testing was undertaken by the innovative test of the dried blood spot ( DBS ) test which increased the rate of testing by 4 fold compared to routine blood testing . Findings SeventyEighty two subjects ( 82 % ) out of the 95 recruited were followed up at 6 months and 62 ( 65 % ) were followed up at 12 months . On the primary outcome measure of the rate of seroconversion , 8 out of 62 patients followed-up at twelve months seroconverted , three in the EPC group and five in the SEC group , indicating incidence rates of 9.1 per 100 person years for the EPC group , 17.2 per 100 person years for the SEC group , and 12.9 per 100 person years for the cohort as a whole . Analysis of the secondary outcome measures on alcohol use , risk behaviour , psychological measures , quality of life , showed no significant differences between the EPC and the SEC groups . However , there were significant changes on a number of measures from baseline values indicating positive change for both groups . Conclusion We were not able to prove the efficacy of EPC in comparison with SEC in the prevention of hepatitis C in IDUs . This was related to low recruitment and retention rates of the participants . Moreover there was a low adherence rate to EPC . The study provided the benefits of developing and introducing behavioural interventions of the EPC and SEC and the DBS screening for Hepatitis C. Moreover the main lessons learnt were that piloting of a new intervention is a crucial first step before conducting pragmatic RCTs of psychological interventions in the field of addiction ; that an infrastructure and culture for psychosocial interventions is needed to enable applied research in the service environment , and research funding is needed for enabling the recruitment of dedicated trained therapists for the delivery of these interventions To help reduce the elevated risk of acquiring HIV for African-American and Latina women drug users in primary heterosexual relationships , we developed a brief couple-based HIV counseling and testing prevention intervention . The intervention was based on an integrated HIV risk behavior theory that incorporated elements of social exchange theory , the theory of gender and power , the stages-of-change model , and the information-motivation-behavior skills model . In this article , we describe the development , content , and format of the couple-based HIV testing and counseling intervention , and its delivery to 110 couples ( 220 individuals ) in a r and omized effectiveness trial , the Harlem River Couples Project , conducted in New York City from 2005 to 2007 . Components of the couple-based intervention included a personalized dyadic action plan based on the couple ’s risk profile and interactive exercises design ed to help build interpersonal communication skills , and facilitated discussion of social norms regarding gender roles . The couple-based HIV testing and counseling intervention significantly reduced women ’s overall HIV risk compared to a st and ard-of-care individual HIV testing and counseling intervention . Experiences and perceptions of the intervention were positive among both clients and interventionists . The study was the first to demonstrate the effectiveness and feasibility of delivering a brief couple-based HIV counseling and testing intervention to reduce risk among drug-using heterosexual couples in high HIV prevalent urban communities in the USA . The intervention can be exp and ed to include new HIV prevention strategies , such as pre-exposure prophylaxis . Further research is needed to evaluate cost-effectiveness and implementation of the intervention in clinical setting BACKGROUND Poor adherence to treatment diminishes its individual and public health benefit . Financial incentives , provided on the condition of treatment attendance , could address this problem . Injecting drug users are a high-risk group for hepatitis B virus ( HBV ) infection and transmission , but adherence to vaccination programmes is poor . We aim ed to assess whether contingency management delivered in routine clinical practice increased the completion of HBV vaccination in individuals receiving opioid substitution therapy . METHODS In our cluster r and omised controlled trial , we enrolled participants at 12 National Health Service drug treatment services in the UK that provided opioid substitution therapy and nurse-led HBV vaccination with a super-accelerated schedule ( vaccination days 0 , 7 , and 21 ) . Clusters were r and omly allocated 1:1:1 to provide vaccination without incentive ( treatment as usual ) , with fixed value contingency management ( three £ 10 vouchers ) , or escalating value contingency management ( £ 5 , £ 10 , and £ 15 vouchers ) . Both contingency management schedules rewarded on-time attendance at appointments . The primary outcome was completion of clinical ly appropriate HBV vaccination within 28 days . We also did sensitivity analyses that examined vaccination completion with full adherence to appointment times and within a 3 month window . The trial is registered with Current Controlled Trials , number IS RCT N72794493 . FINDINGS Between March 16 , 2011 , and April 26 , 2012 , we enrolled 210 eligible participants . Compared with six ( 9 % ) of 67 participants treated as usual , 35 ( 45 % ) of 78 participants in the fixed value contingency management group met the primary outcome measure ( odds ratio 12·1 , 95 % CI 3·7 - 39·9 ; p<0·0001 ) , as did 32 ( 49 % ) of 65 participants in the escalating value contingency management group ( 14·0 , 4·2 - 46·2 ; p<0·0001 ) . These differences remained significant with sensitivity analyses . INTERPRETATION Modest financial incentives delivered in routine clinical practice significantly improve adherence to , and completion of , HBV vaccination programmes in patients receiving opioid substitution therapy . Achievement of this improvement in routine clinical practice should now prompt actual implementation . Drug treatment providers should employ contingency management to promote adherence to vaccination programmes . The effectiveness of routine use of contingency management to achieve long-term behaviour change remains unknown . FUNDING National Institute for Health Research ( RP-PG-0707 - 10149 ) OBJECTIVES Public health initiatives have lowered human immunodeficiency virus ( HIV ) transmission risk associated with injection drug use in the United States , making sexual risk behaviors a greater source of transmission . Strategies are therefore needed to reduce these risk behaviors among all emergency department ( ED ) patients who use drugs , regardless of route of administration . Although recent articles have focused on the opportunity for early HIV detection and treatment through an array of ED screening and testing strategies , the effect of voluntary HIV testing and brief counseling ( VT/C ) on the sexual behaviors of out-of-treatment drug users over time has not yet been reported . METHODS From November 2004 to May 2008 , the study screened 46,208 urban ED patients aged 18 to 54 years ; 2,148 ( 4.6 % ) reported cocaine or heroin use within 30 days , 1,538 met eligibility criteria ( Drug Abuse Severity Test [ DAST ] scores ≥3 and were either English- or Spanish-speaking ) , and 1,030 were enrolled . These data were obtained in the course of a r and omized , controlled trial ( Project SAFE ) of a brief motivational intervention focused on reducing risky sexual behaviors . Although the intervention itself did not demonstrate any differential effect on the number or percentage of unprotected sexual acts , both control and intervention group participants received baseline VT/C and referral for drug treatment as part of the study protocol . This study is a report of a secondary analysis of cohort data to describe changes in sexual behaviors over time among drug users after the VT/C and referral . RESULTS The mean ( ±SD ) age of enrollees was 35.8 ( ±8.4 ) years ; 67 % were male , 39 % were non-Hispanic black or African American , 41 % were white non-Hispanic , and 19 % were Hispanic . Half injected drugs , and 53 % met criteria for posttraumatic stress disorder ( PTSD ) . At baseline testing , 8.8 % were HIV-positive on enzyme-linked immunosorbent assay . Follow-ups were conducted at 6 and 12 months , with an attrition rate of 22 % . Known HIV-positive patients accounted for 84 of 1,030 cases ( 8.1 % ) , and 13 new cases were discovered : 7 of 946 at were discovered at the baseline contact ( 0.74 % ) , 2 of 655 were discovered at 6 months ( 0.3 % ) , and 4 of 706 ( 0.57 % ) were discovered at the 12-month contact . Twelve of the 13 returned for confirmatory testing and were actively enrolled in our infectious disease clinic . For all partners , there was a reduction in the percentage of unprotected sex acts over time ( p < 0.0001 ) , with decreases at 6 months versus baseline ( odds ratio [ OR ] = 0.70 , 95 % confidence interval [ CI ] = 0.60 to 0.83 ) , sustained at 12 months versus baseline ( OR = 0.69 , 95 % CI = 0.58 to 0.82 ) . For the outcome of percentage of sex acts while high , there was also a significant reduction over time ( p < 0.0001 ) , with a drop-off at 6 months versus baseline ( OR = 0.31 , 95 % CI = 0.25 to 0.37 ) that was sustained at 12 months ( OR vs. baseline 0.25 , 95 % CI = 0.20 to 0.30 ) . In an adjusted model , male sex , older age , and HIV positivity predicted significant declines over time in the likelihood of unprotected sexual acts . Older age and higher baseline drug severity predicted significant decreases over time in the likelihood of sex acts while high . CONCLUSIONS Voluntary testing and counseling for HIV or sexually transmitted infections , accompanied by referral to drug treatment , for this population of ED cocaine and heroin users was associated with reduction in unprotected sex acts and fewer sex acts while high There is a need for brief HIV prevention interventions that can be disseminated and implemented widely . This article reports the results of a small r and omized field experiment that compared the relative effects of a brief two-session counselor-delivered computer-tailored intervention and a control condition . The intervention is design ed for use with African-American , non-Hispanic white and Hispanic males and females who may be at risk of HIV through unprotected sex , selling sex , male to male sex , injecting drug use or use of stimulants . Participants ( n = 120 ) were recruited using a quota sampling approach and r and omized using block r and omization , which result ed in ten male and ten female participants of each racial/ethnic group ( i.e. African-American , non-Hispanic white and Hispanic ) being assigned to either the intervention or a control arm . In logistic regression analyses using a generalized estimating equations approach , at 3-month followup , participants in the intervention arm were more likely than participants in the control arm to report condom use at last sex ( Odds ratio [ OR ] = 4.75 ; 95 % Confidence interval [ CI ] = 1.70–13.26 ; p = 0.003 ) . The findings suggest that a brief tailored intervention may increase condom use . Larger studies with longer followups are needed to determine if these results can be replicated Intravenous drug use is a major vector of HIV transmission . We assessed whether contingency management ( CM ) , in which participants earn reinforcers for drug abstinence , reduces HIV risk behaviors in methadone-maintained opiate- and cocaine-using out patients . Participants ( n=116 ) were r and omly assigned to prize-based CM or to receipt of prize draws noncontingently on a schedule yoked to the CM group . Both groups received methadone and individual counseling throughout treatment . The HIV-Risk Taking Behaviour Scale was administered in written question naire form at 2-week intervals ( HRBS ; [ Darke , S. , Hall , W. , Heather , N. , Ward , J. , & Wodak , A. ( 1991 ) . The reliability and validity of a scale to measure HIV risk-taking behaviour among intravenous drug users . AIDS , 5 , 181 - 185 ] ) . A mediation analysis was conducted to determine whether abstinence from opiates and cocaine mediated the effect of CM on HRBS scores . Changes in HRBS scores over time differed significantly by treatment ( F(9,334)=2.4 , p<0.05 ) , with HRBS scores decreasing over time in the CM group to a greater extent than in the noncontingent control group . Participants in the CM group had significantly lower rates of simultaneous cocaine/opiate-positive urine specimens than those in the noncontingent control group during CM treatment ( F(1,111)=6.8 , p=0.01 ) . The relationship between treatment condition and HRBS scores was mediated by abstinence . CM targeted toward cocaine and heroin use produces significant reductions in injection-related drug-taking behaviors associated with heightened risk for getting or transmitting HIV Introduction Injecting drug use is a primary driver of HIV epidemics in many countries . People who inject drugs ( PWID ) and are HIV infected are often doubly stigmatized and many encounter difficulties reducing risk behaviors . Prevention interventions for HIV-infected PWID that provide enhanced support at the individual , family , and community level to facilitate risk-reduction are needed . Methods 455 HIV-infected PWID and 355 of their HIV negative injecting network members living in 32 sub-districts in Thai Nguyen Province were enrolled . We conducted a two-stage r and omization : First , sub-districts were r and omized to either a community video screening and house-to-house visits or st and ard of care educational pamphlets . Second , within each sub-district , participants were r and omized to receive either enhanced individual level post-test counseling and group support sessions or st and ard of care HIV testing and counseling . This result ed in four arms : 1 ) st and ard of care ; 2 ) community level intervention ; 3 ) individual level intervention ; and 4 ) community plus individual intervention . Follow-up was conducted at 6 , 12 , 18 , and 24 months . Primary outcomes were self-reported HIV injecting and sexual risk behaviors . Secondary outcomes included HIV incidence among HIV negative network members . Results Fewer participants reported sharing injecting equipment and unprotected sex from baseline to 24 months in all arms ( 77 % to 4 % and 24 % to 5 % respectively ) . There were no significant differences at the 24-month visit among the 4 arms ( Wald = 3.40 ( 3 df ) ; p = 0.33 ; Wald = 6.73 ( 3 df ) ; p = 0.08 ) . There were a total of 4 HIV seroconversions over 24 months with no significant difference between intervention and control arms . Discussion Underst and ing the mechanisms through which all arms , particularly the control arm , demonstrated both low risk behaviors and low HIV incidence has important implication s for policy and prevention programming . Trial Registration Clinical Trials.gov Pilot studies play an important role in health research , but they can be misused , mistreated and misrepresented . In this paper we focus on pilot studies that are used specifically to plan a r and omized controlled trial ( RCT ) . Citing examples from the literature , we provide a method ological framework in which to work , and discuss reasons why a pilot study might be undertaken . A well-conducted pilot study , giving a clear list of aims and objectives within a formal framework will encourage method ological rigour , ensure that the work is scientifically valid and publishable , and will lead to higher quality RCTs . It will also safeguard against pilot studies being conducted simply because of small numbers of available patients We analyzed data from a large r and omized HIV/HCV prevention intervention trial with young injection drug users ( IDUs ) conducted in five U.S. cities . The trial compared a peer education intervention ( PEI ) with a time-matched , attention control group . Applying categorical latent variable analysis ( mixture modeling ) to baseline injection risk behavior data , we identified four distinct classes of injection-related HIV/HCV risk : low risk , non-syringe equipment-sharing , moderate-risk syringe-sharing , and high-risk syringe-sharing . The trial participation rate did not vary across classes . We conducted a latent transition analysis using trial baseline and 6-month follow-up data , to test the effect of the intervention on transitions to the low-risk class at follow-up . Adjusting for gender , age , and race/ethnicity , a significant intervention effect was found only for the high-risk class . Young IDU who exhibited high-risk behavior at baseline were 90 % more likely to be in the low-risk class at follow-up after the PEI intervention , compared to the control group Background With HIV prevalence estimated at 20 % among female injecting drug users ( IDUs ) in St. Petersburg , Russia , there is a critical need to address the HIV risks of this at-risk population . This study characterized HIV risks associated with injecting drug use and sex behaviors and assessed the initial feasibility and efficacy of an adapted Woman-Focused intervention , the Women 's CoOp , relative to a Nutrition control to reduce HIV risk behaviors among female IDUs in an inpatient detoxification drug treatment setting . Method Women ( N = 100 ) were r and omized into one of two one-hour long intervention conditions -- the Woman-Focused intervention ( n = 51 ) or a time and attention-matched Nutrition control condition ( n = 49 ) . Results The results showed that 57 % of the participants had been told that they were HIV-positive . At 3-month follow-up , both groups showed reduced levels of injecting frequency . However , participants in the Woman-Focused intervention reported , on average , a lower frequency of partner impairment at last sex act and a lower average number of unprotected vaginal sex acts with their main sex partner than the Nutrition condition . Conclusion The findings suggest that improvements in sexual risk reduction are possible for these at-risk women and that more comprehensive treatment is needed to address HIV and drug risks in this vulnerable population The efficacy of Safety Counts , a CDC-diffused intervention , was reanalyzed . In a quasi experimental , cross-over design , injection drug users ( IDU ) and crack users in two neighborhoods were assigned by neighborhood to receive individual Voluntary HIV Counseling and Testing or Safety Counts and 78 % were reassessed at 5–9 months . Drug users in the Safety Counts program reported significantly greater reductions in risky sex , crack and hard drug use , and risky drug injection . The more sessions of Safety Counts attended , the greater were the reductions in risky acts . Different analytic decisions result in very different findings for the same intervention . Safety Counts is an effective intervention for IDU and crack users . Analytic decision of intervention outcomes is highly related to evaluations of an intervention ’s efficacy We analyzed data from a large r and omized HIV/HCV prevention intervention trial with young injection drug users ( IDUs ) . Using categorical latent variable analysis , we identified distinct classes of sexual behavior for men and women . We conducted a latent transition analysis to test the effect of the intervention on transitions from higher to lower risk classes . Men who were in a high-risk class at baseline who received the intervention were 86 % more likely to be in a low-risk class at follow-up compared to those in the control group ( p = 0.025 ) . High-risk intervention participants were significantly more likely to transition to the class characterized by unprotected sex with a main partner only , while low-risk intervention participants were significantly less likely to transition to that class . No intervention effect was detected on the sexual risk behavior of women , or of men who at baseline were having unprotected sex with a main partner only . ResumenAnalizamos los datos de un ensayo grade de intervención aleatorizado de prevención del VIH/VHC con jóvenes usuarios de drogas inyectables ( UDI ) , Utiliz and o el análisis de variable latente categórico , se identificaron distintas clases de comportamiento sexual para hombres y mujeres . Se realizó un análisis de transición latente para probar el efecto de la intervención sobre las transiciones de alto riesgo a las clases de menor riesgo . Los hombres que estaban en una clase de alto riesgo al inicio del estudio que recibieron la intervención eran 86 % más propensos a estar en una clase de bajo riesgo durante el seguimiento en comparación con los del grupo control ( p = 0.025 ) . Participantes en la intervención de alto riesgo tuvieron significativamente más probabilidades de transición a la clase que se caracteriza por relaciones sexuales sin protección con sólo una pareja principal , mientras que los participantes de intervención de bajo riesgo tuvieron significativamente menos probabilidades de transición a esa clase . Ningún efecto de la intervención fue detectado en el comportamiento de riesgo sexual de las mujeres o de los hombres que al inicio del estudio estaban teniendo relaciones sexuales sin protección con una pareja principal solamente OBJECTIVES We examined whether frequent drug use increases the likelihood of subsequent sexual or physical intimate partner violence ( IPV ) and whether IPV increases the likelihood of subsequent frequent drug use . METHODS A r and om sample of 416 women on methadone was assessed at baseline ( wave 1 ) and at 6 months ( wave 2 ) , and 12 months ( wave 3 ) following the initial assessment . Propensity score matching and multiple logistic regression were employed . RESULTS Women who reported frequent crack use at wave 2 were more likely than non-drug using women to report IPV at wave 3 ( odds ratio [OR]=4.4 ; 95 % confidence interval [CI]=2.1 , 9.1 ; P<.01 ) , and frequent marijuana users at wave 2 were more likely than non-drug users to report IPV at wave 3 ( OR=4.5 ; 95 % CI=2.4 , 8.4 ; P<.01 ) . In addition , women who reported IPV at wave 2 were more likely than women who did not report IPV to indicate frequent heroin use at wave 3 ( OR=2.7 ; 95 % CI=1.1 , 6.5 ; P=.04 ) . CONCLUSIONS Our findings suggest that the relationship between frequent drug use and IPV is bidirectional and varies by type of drug OBJECTIVE A previous pilot trial evaluating computer-based training for cognitive-behavioral therapy ( CBT4CBT ) in 77 heterogeneous substance users ( alcohol , marijuana , cocaine , and opioids ) demonstrated preliminary support for its efficacy in the context of a community-based outpatient clinic . The authors conducted a more definitive trial in a larger , more homogeneous sample . METHOD In this r and omized clinical trial , 101 cocaine-dependent individuals maintained on methadone were r and omly assigned to st and ard methadone maintenance or methadone maintenance with weekly access to CBT4CBT , with seven modules delivered within an 8-week trial . RESULTS Treatment retention and data availability were high and comparable across the treatment conditions . Participants assigned to the CBT4CBT condition were significantly more likely to attain 3 or more consecutive weeks of abstinence from cocaine ( 36 % compared with 17 % ; p<0.05 , odds ratio=0.36 ) . The group assigned to CBT4CBT also had better outcomes on most dimensions , including urine specimens negative for all drugs , but these reached statistical significance only for individuals completing the 8-week trial ( N=69 ) . Follow-up data collected 6 months after treatment termination were available for 93 % of the r and omized sample ; these data indicate continued improvement for those assigned to the CBT4CBT group , replicating previous findings regarding its durability . CONCLUSIONS This trial replicates earlier findings indicating that CBT4CBT is an effective adjunct to addiction treatment with durable effects . CBT4CBT is an easily disseminable strategy for broadening the availability of CBT , even in challenging population s such as cocaine-dependent individuals enrolled in methadone maintenance programs This study examined the relationship between sex trading and psychological distress among a nonr and om sample of women recruited from 3 methadone maintenance clinics in New York City . Face-to-face interviews with 280 women ( M age = 40.7 ) revealed that 32 % had traded sex for money or drugs in the previous year . Compared to other participants , these women reported less education and higher rates of incarceration in the past year , sexually transmitted diseases , childhood sexual abuse , partner abuse , and current regular crack/cocaine and alcohol use . Hierarchical multiple regression analysis indicated that sex traders scored 0.41 units higher than non-sex traders on the General Severity Index of the Brief Symptom Inventory after controlling for all relevant covariates . The findings emphasize the need to consider the interrelation of psychological distress , abuse , and addiction in design ing public health interventions addressing methadone maintained women Beginning in the mid-1990s , the widespread use of effective treatments for HIV infection ( highly active antiretroviral therapy [ HAART ] ) led first to dramatic declines in AIDS incidence and deaths and then to changes in the priorities for HIV prevention and treatment . The prospect s for people living with HIV infection changed from expectation of premature death to the likelihood of living a longer healthier life . With widespread availability of HAART , HIV infection is now treated as a chronic disease . With substantially increased survival , the number of people living with HIV in the United States increased to an estimated 1 million in 2003 . In the United States , the increasing numbers of people living with HIV brought new urgency and opportunities to develop secondary HIV prevention initiatives for people living with HIV . In 2003 , the Centers for Disease Control and Prevention ( CDC ) introduced the Advancing HIV Prevention initiative , which included the objective of preventing new infections by working with persons diagnosed with HIV and their partners , Also , in 2003 , the CDC and the Health Re sources and Services Administration ( HRSA ) called for increased HIV prevention efforts in the medical care of persons living with HIV . Even so , the literature of published prevention interventions for people living with HIV is limited . Two meta-analyses of HIV prevention studies among persons living with HIV were published in 2006 . In the 12 studies that met inclusion criteria , Crepaz and colleagues found that there was evidence of significant reductions in unprotected sex and decreased acquisition of sexually transmitted infections . Only 1 of these studies targeted injection drug users ( IDUs ) . Among the 15 studies of interventions to prevent sexual transmission from HIV-positive persons that met inclusion criteria , Johnson and colleagues found that the interventions led to improved use of condoms but not to reducing the number of sex partners . For people living with HIV , utilizing health care well and , when antiretroviral treatment is needed , adhering to medications schedules also are important . Being able to take multiple antiretroviral medications as prescribed and to sustain good adherence for years is essential to avoid developing resistance to 1 or more of the medications and potentially serious complications of HIV infection . For those reasons , the Interventions for Seropositive Injectors— Research and Evaluation ( INSPIRE ) research project was a major step in testing behavioral interventions for people living with HIV . The INSPIRE project was planned in the late 1990s and was in the field from 2001 to 2005 . It was a carefully design ed and well-implemented r and omized controlled trial of a behavioral intervention with 966 HIV-infected IDUs , a group of people living with HIV that is less frequently studied . INSPIRE was jointly funded by the CDC and HRSA to integrate testing of behavioral interventions in 2 high-priority areas , prevention of secondary transmission and improving HIV-related health care . INSPIRE was a theory-based trial of a 10-session peer mentoring intervention , including 7 small group and 2 individual sessions and a community visit to practice This r and omized , controlled trial , conducted among out-of-treatment heroin/cocaine users at an emergency department visit , tests the impact on sexual risk of adding brief motivational intervention ( B-MI ) to point-of-service testing , counseling and drug treatment referral . 1,030 enrollees aged 18–54 received either voluntary counseling/testing ( VC/T ) with drug treatment referral , or VC/T , referral , and B-MI , delivered by an outreach worker . We measured number and proportion of non-protected sex acts ( last 30 days ) at 6 and 12 months ( n = 802 ) . At baseline , 70 % of past-30-days sex acts were non-protected ; 35 % of sex acts occurred while high ; 64 % of sexual acts involved main , 24 % casual and 12 % transactional sex partners ; 1.7 % tested positive for an STI , and 8.8 % for HIV . At six or 12 month follow-up , 20 enrollees tested positive for Chlamydia and /or Gonorrhea , and 6 enrollees HIV sero-converted . Self-reported high-risk behaviors declined in both groups with no significant between-group differences in behaviors or STI/HIV incidence AIM We tested the efficacy of a brief intervention based on motivational interviewing ( MI ) to reduce high-risk injection behaviours over a 6-month period among people who inject drugs ( PWID ) . DESIGN A single-site two-group parallel r and omized controlled trial comparing MI with a brief educational intervention ( EI ) . SETTING A study office located in downtown Montréal , Canada , close to the community-based harm reduction programmes where PWID were recruited . PARTICIPANTS PWID who had shared drug injection equipment or shared drugs by backloading or frontloading in the month prior to recruitment were r and omized to either the MI ( 112 ) or EI ( 109 ) groups . INTERVENTION The MI aim ed to ( 1 ) encourage PWID to voice their desires , needs and reasons to change behaviours ; ( 2 ) boost motivation to change behaviours ; and ( 3 ) when the person was ready , support the plan he or she chose to reduce injection risk behaviours . The EI consisted of an individual session about safe injection behaviours . MEASUREMENTS The primary outcome was defined as having any of these risk behaviours at 6 months : having shared syringes , containers , filters or water to inject drugs in the previous month and backloading/frontloading ; each behaviour was examined separately , as secondary outcomes . FINDINGS The probability of reporting a risk injection behaviour decreased in both the MI and the EI groups . At 6-month follow-up , participants who reported any risk behaviours were 50 % [ odds ratio ( OR ) = 0.50 ; confidence interval ( CI ) = 0.13 - 0.87 ] less likely to be in the MI group than in the EI group as well as those who reported sharing containers ( OR = 0.50 ; CI = 0.09 - 0.90 ) . PWID who reported sharing equipment excluding syringes were 53 % less likely to be in the MI group ( OR = 0.47 ; CI = 0.11 - 0.84 ) . CONCLUSIONS A brief motivational interviewing intervention was more effective than a brief educational intervention in reducing some high risk injecting behaviours up in the subsequent 6 months Methadone maintenance programs ( MMP ) have the potential to play an important role in reducing HIV risk , given the appropriate type and level of ancillary treatments . In this study , we investigated the efficacy of a 12-session harm reduction group intervention for injection drug users , based upon the Information-Motivation-Behavioral skills model of behavior change , that focused on reducing both drug and sex risk . Two hundred and twenty patients entering an MMP were r and omized to receive either st and ard care (SC)-2 hours of counseling per month and a single-session risk reduction intervention-or SC plus the harm reduction group ( HRG ) . Results showed that during treatment , patients receiving HRG were more likely to be abstinent from cocaine and to report fewer unsafe sexual practice s. Post-treatment , HRG patients scored higher on a sexual risk quiz and reported increased self-efficacy in high risk sexual situations . Enhancing methadone maintenance with a weekly harm reduction group treatment was somewhat more expensive but can bring about positive changes in behaviors and attitudes that are associated with the transmission of HIV Cocaine use is associated with injecting and sexual HIV risk behaviors . This study was a r and omized controlled trial of behavioral interventions for cocaine dependence and HIV risk behaviors among dually ( cocaine and heroin ) dependent out patients . Methadone maintenance was augmented with cognitive-behavioral therapy ( CBT ) , contingency management ( CM ) , both ( CBT+CM ) , or neither . The study sample ( n=81 ) was 52 % female , 70 % African American , and 37.9+/-7.0 years old . Proportions reporting HIV risk behaviors at intake were : 96.3 % ( 78/81 ) injection drug use , 56.8 % ( 46/81 ) sharing needles , 30.9 % ( 25/81 ) unprotected sex , 28.4 % ( 23/81 ) trading sex for money or drugs . Proportions who no longer reported behaviors at study exit were : 51.3 % ( 40/78 ) injection drug use , 91.3 % ( 42/46 ) sharing needles , 88 % ( 22/25 ) unprotected sex , 91.3 % ( 21/23 ) trading sex for money or drugs . Participants receiving CBT+CM were more likely to report cessation of unprotected sex relative to control ( OR=5.44 , 95 % CI 1.14 - 26.0 , p=0.034 ) but this effect was no longer significant after adjusting for drug-negative urines . These results suggest broad beneficial effects of methadone maintenance augmented with behavioral interventions for reducing HIV risk behaviors A community-based HIV intervention for African-American women who are active injection drug users ( IDUs ) was evaluated . Seventy-one women ( aged 20–54 years ) were r and omly assigned to one of two enhanced gender- and culturally specific intervention conditions or to the NIDA st and ard condition . Substantial decreases ( p < .001 ) were found in the frequency of drug use and the frequency of drug injection as well as in the sharing of injection works or water and the number of injections . Trading sex for drugs or money , having sex while high , as well as other sexual risk behaviors were also reduced significantly . Furthermore , women in both enhanced intervention conditions were more likely to reduce their drug-using and sexual risk behaviors than were women in the st and ard condition . Results indicate the value of including additional components in interventions design ed to reduce the risk of infection with HIV among women who inject drugs We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users ( IDUs ) and their drug and /or sexual networks . A r and omized controlled trial was conducted in St. Petersburg , Russia among IDU index participants and their risk network participants . Network units were r and omized to the control or experimental intervention . Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members . Analysis includes 76 index and 84 network participants who were HIV uninfected . The main outcome measure was HIV sero-conversion . The incidence rates in the control and experimental groups were 19.57 ( 95 % CI 10.74–35.65 ) and 7.76 ( 95 % CI 3.51–17.19 ) cases per 100 p/y , respectively . The IRR was 0.41 ( 95 % CI 0.15–1.08 ) without a statistically significant difference between the two groups ( log rank test statistic X2 = 2.73 , permutation p value = 0.16 ) . Retention rate was 67 % with a third of the loss due to incarceration or death . The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs BACKGROUND Injection drug users ( IDUs ) who also smoke crack may be at greatest risk for infection with HIV as well as other blood-borne and sexually transmitted infections and in most need of positive behavioral changes . METHODS Three hundred and thirty-three women ( aged 18 - 59 years ) were r and omly assigned to one of two enhanced gender- and culturally specific HIV intervention conditions or to the NIDA st and ard condition . Of primary interest in this study were baseline risk and intervention response rates among three groups of drug users -- IDUs who did not smoke crack , IDUs who did smoke crack , and crack smokers who did not inject . Univariate and multivariate methods were utilized , including generalized estimating equations . RESULTS The intervention produced positive behavioral changes over time , but response rates varied according to drug using group . Overall , women falling into the crack smoking IDU category appeared to be less responsive to the intervention than those in the other drug using groups , and participants in the crack smoking only group were less responsive than those in the IDU only group . CONCLUSIONS Results presented here indicate the continuing need to develop and target effective interventions to particular subgroups of high-risk individuals who may be most resistant to change AIMS To assess the effectiveness of a peer-based , personal risk network-focused HIV prevention intervention to ( i ) train injection drug users ( IDUs ) to reduce injection and sex risk behaviors , ( ii ) conduct outreach to behaviorally risky individuals in their personal social networks [ called risk network members ( RNM ) ] , and ( iii ) reduce RNM HIV risk behaviors . DESIGN R and omized controlled trial with prospect i ve data collection at 6 , 12 and 18 months . Intervention condition consisted of five group sessions , one individual session and one session with Index and the RNM . SETTING This study was conducted in Baltimore , Maryl and from March 2004 to March 2006 . PARTICIPANTS ( i ) Index participants were aged ≥ 18 years and self-reported injection drug use in the prior 6 months and ( ii ) their RNM who were aged ≥ 18 years and drug users or sex partners of Index . MEASUREMENTS Outcomes included : ( i ) injection risk based on sharing needles , cookers and cotton for injection and drug splitting , ( ii ) sex risk based on number of sex partners , condom use and exchanging sex and ( iii ) Index HIV outreach behaviors . FINDINGS A total of 227 Index participants recruited 336 RNM . Retention of Index at 18-month follow-up exceeded 85 % . Findings suggest that the experimental condition was efficacious at 18 months in reducing Index participant injection risk [ odds ratio ( OR ) = 0.38 ; 95 % confidence interval ( CI ) = 0.18 - 0.77 ) , drug-splitting risk ( OR = 0.46 ; 95 % CI = 0.25 - 0.88 ) and sex risk among Index ( OR = 0.53 ; 95 % CI = 0.34 - 0.86 ) . Significant intervention effect on increased condom use among female RNM was observed ( OR = 0.34 ; 95 % CI = 0.18 - 0.62 ) . CONCLUSIONS Training active IDU to promote HIV prevention with behaviorally risky individuals in their networks is feasible , efficacious and sustainable Background Behavioral interventions to address the complex medical and HIV risk reduction needs of HIV-seropositive ( HIV-positive ) injection drug users ( IDUs ) are urgently needed . We describe the development of Interventions for Seropositive Injectors— Research and Evaluation ( INSPIRE ) , a r and omized controlled trial of an integrated intervention for HIV-positive IDUs , and the characteristics of the baseline sample . Methods HIV-positive IDUs were recruited from community setting s in 4 US cities . After completing a baseline assessment , participants who attended the first session were r and omly assigned to ( 1 ) a 10-session peer mentoring intervention design ed to improve utilization of HIV care , to improve adherence to HIV medications , and to reduce sexual and injection risk or ( 2 ) an 8-session videotape control . Periodic follow-up for 12 months is ongoing . Results A total of 1161 HIV-positive IDUs completed the baseline assessment , and 966 ( 83 % ) were r and omized . Retention rates are greater than 80 % for all follow-up periods . Approximately 79 % of baseline participants reported a recent medical visit , 49 % were taking highly active antiretroviral therapy , and 19 % had an undetectable viral load . Use of injection and noninjection substances was prevalent , and sexual and injection risks were each reported by more than 25 % of participants . Conclusion There is a need for an integrated intervention for HIV-positive IDUs , and these data show the acceptability of such an approach Objective : We recently showed efficacy of an intervention to increase condom use among female sex workers ( FSWs ) in Tijuana and Ciudad Juarez , situated on the Mexico-United States border . We determined whether increases in condom use were predicted by social cognitive theory and injection drug user status among women r and omized to this intervention . Methods : Four hundred nine HIV-negative FSWs aged ≥18 years having unprotected sex with clients within the prior 2 months received a brief individual counseling session integrating motivational interviewing and principles of behavior change ( ie , HIV knowledge , self-efficacy for using condoms , and outcome expectancies ) . Results : Increases in self-efficacy scores were associated with increases in percent condom use ( P = 0.008 ) , whereas outcome expectancies were not . Female sex workers who inject drugs ( FSW-IDUs ) increased condom use with clients but not to the same extent as other FSWs ( P = 0.09 ) . Change in HIV knowledge was positively associated with change in percent condom use among FSW-IDUs ( P = 0.03 ) but not noninjection drug users . Conclusions : Increases in self-efficacy significantly predicted increased condom use among FSWs , consistent with social cognitive theory . Increased HIV knowledge was also important among FSW-IDUs , but their changes in condom use were modest . Enhanced interventions for FSW-IDUs are needed , taking into account realities of substance use during sexual transactions that can compromise safer sex negotiation Existing evidence -based HIV risk reduction interventions have not been design ed for implementation within clinical setting s , such as methadone maintenance programs , where many high-risk drug users seek treatment services . We therefore systematic ally developed an adapted , significantly shortened , version of a comprehensive evidence -based intervention called the Community-friendly Health Recovery Program ( CHRP ) which has demonstrated preliminary evidence of efficacy in a feasibility/acceptability study already published . In a r and omized controlled trial reported here , we tested the efficacy of the CHRP intervention among high-risk drug users newly enrolled in drug treatment at an inner-city methadone maintenance program . The CHRP intervention produced improvements in drug risk reduction knowledge as well as demonstrated sex- and drug-risk reduction skills . Support was found for the IMB model of health behavior change . Implication s for future intervention research and practice are considered . ResumenIntervenciones riesgo del VIH existentes reducción del basada en la evidencia no han sido diseñadas para aplicación en context os clínicos , tales como programas de mantenimiento con metadona , donde muchos usuarios de drogas de alto riesgo buscan servicios de tratamiento . Por lo tanto desarrollamos sistemáticamente una versión adaptada , acortada significativamente , de una intervención integral basada en la evidencia llamada la comunidad ambiente salud recuperación programa ( CHRP ) que ha demostrado la evidencia preliminar de eficacia en un estudio de viabilidad/aceptabilidad ya publicado . En un ensayo controlado aleatorio ( ECA ) divulgado aquí , hemos probado la eficacia de la intervención CHRP entre usuarios de drogas de altoriesgo recién matriculados en el tratamiento de drogas en un programa de mantenimiento con metadona del centro de la ciudad . La intervención CHRP produjeron mejorías en el conocimiento de reducción de riesgo de drogas así como había demostrado capacidades de reducción de riesgo de sexo y drogas . Apoyo encontró para el modelo IMB de cambio de comportamiento de salud . Implicaciones para futuras intervenciones investigación y la práctica se consideran Background : Requiring help injecting has been associated with syringe sharing among injection drug users ( IDUs ) . No prospect i ve study has fully examined this risk factor and its relation to rates of HIV infection . We investigated whether requiring help injecting illicit drugs was a predictor of HIV infection among a prospect i ve cohort of IDUs . Methods : The Vancouver Injection Drug User Study is a prospect i ve study of more than 1500 IDUs who have been recruited from the Downtown Eastside of Vancouver since May 1996 . At baseline and semiannually , subjects provided blood sample s and completed an interviewer-administered question naire . The question naire elicits demographic data as well as information about drug use , HIV risk behavior , and drug treatment . HIV incidence rates were calculated using Kaplan-Meier methods , and Cox regression determined independent predictors of seroconversion . Results : A total of 1013 baseline HIV-negative participants were eligible for this study . Within this population , 418 ( 41.3 % ) participants had required help injecting during the last 6 months at baseline . Participants requiring help injecting were more likely to be female ( odds ratio = 2.3 , 95 % confidence interval [ CI ] : 1.8 - 3.0 ; P < 0.001 ) , were slightly younger ( 33.5 vs. 34.9 years of age ; P = 0.014 ) , and had fewer years of experience injecting drugs ( 7 vs. 11 years ; P ≤ 0.001 ) . Among participants who required help injecting at baseline , cumulative HIV incidence at 36 months was 16.1 % compared with 8.8 % among participants who did not require help injecting ( log-rank , P < 0.001 ) . In an adjusted model controlling for potential confounding variables , being aboriginal ( relative hazard [ RH ] = 1.68 , 95 % CI : 1.15 - 2.48 ) , injecting cocaine daily ( RH = 2.71 , 95 % CI : 1.87 - 3.95 ) , and requiring help injecting ( RH = 1.79 , 95 % CI : 1.23 - 2.62 ) remained independent predictors of HIV seroconversion . Conclusions : These data demonstrate the need for interventions to reduce the risk of HIV infection among IDUs who require help injecting We studied the receptivity of a population of HIV-infected patients to the development of a group educational intervention in order to enhance the adherence to therapy . We design ed a group educational activity conducted by family physicians and directed to patients with HIV infection treated with antiretrovirals for at least six months . We conducted a r and omized trial that compared two interventions : an educational intervention plus individual counsel or the last option alone . We studied their clinical situation , adherence to therapy and familial support . We offered 115 patients ( 66.9 % injection drug users ( IDUs ) , 69.6 % males ) the opportunity to be included in our trial , but 73.9 % of them refused . No group with four or more participants was formed . Fifty-nine per cent refused to be included cl aim ing personal reasons and 32.9 % cited trouble in their jobs . There was a non-significant trend to accept in the case of women ( p = 0.19 ) , patients with AIDS ( p = 0.11 ) and non-adherent patients ( p = 0.08 ) . This trend was significant in the group of women with AIDS ( p = 0.01 ) and non-adherent women ( p = 0.05 ) . We concluded that HIV-infected patients , mainly IDUs , are not receptive to group educational programmes . The design of future interventions must take into account the patients ' characteristics AIM To assess the feasibility of a r and omized clinical trial of supervised injectable versus oral methadone maintenance and to assess medium-term treatment outcomes . DESIGN R and omized clinical trial of supervised injectable versus supervised oral methadone maintenance treatment ( MMT ) . Trial participants were dependent illicit opiate injectors allocated at intake to supervised injectable or oral methadone maintenance treatment . SETTING Specialist addictions treatment centre in South London . SUBJECTS Forty dependent illicit opiate injectors seeking methadone maintenance treatment . INTERVENTIONS Daily supervised injectable and oral methadone maintenance , delivered at the treatment centre . MAIN OUTCOME MEASURES Frequency of illicit heroin use and frequency of illicit drug injecting during 30 days before intake to treatment and prior to 6-month follow-up . SECONDARY OUTCOME MEASURES frequency of use of illicit methadone , crack cocaine , benzodiazepines and alcohol , physical and psychological health symptoms and acquisitive crime . RESULTS Injectable and oral MMT were both generally acceptable to the study participants : there was a high level of agreement to enter the r and omized trial , and subsequent retention in treatment was good . The average number of days of illicit heroin use reduced from 22.2 to 7.6 for the injectable MMT group and from 22.4 to 8.7 for the oral MMT group . The average number of days of illicit injecting reduced from 25.7 to 10.8 days for the injectable group and from 20.1 to 11.9 days for the oral group . Patients ' physical and psychological health symptoms and involvement in acquisitive crime also reduced in both groups . Treatment satisfaction ratings at follow-up were higher among patients in the injectable MMT group . The ratio for the actual medication costs between injectable and oral MMT was 6.8:1 , and for the direct operational costs was 4.7:1 . There was some evidence of a differential patient response with greater reductions in heroin use occurring among patients who were daily illicit injectors and had poorer psychological and physical health ( at entry ) who were allocated to injectable MMT . CONCLUSIONS Conduct of the trial has demonstrated that it is feasible to implement supervised injectable methadone maintenance treatment in the context of ( although separate from ) a specialist oral methadone maintenance service . Patients assigned to receive either supervised injectable or oral MMT had broadly equivalent , positive during-treatment outcomes at 6-month follow-up . Future studies should seek to identify patient characteristics which are linked to good outcome in injectable MMT . Practical evidence -based guidance to physicians about determining which patients are more suitable for injectable MMT is urgently needed AIMS Methadone maintenance treatment has been made available in China in response to the rapid spread of human immunodeficiency virus ( HIV ) , but high rates of dropout and relapse are problematic . The aim of this study was to apply and test if a contingency management ( or motivational incentives ) intervention can improve treatment retention and reduce drug use . DESIGN R and om assignment to usual care with ( n = 160 ) or without ( n = 159 ) incentives during a 12-week trial . Incentives participants earned draws for a chance to win prizes on two separate tracks targeting opiate-negative urine sample or consecutive attendance ; the number of draws increased with continuous abstinence or attendance . SETTING Community-based methadone maintenance clinics in Shanghai and Kunming . PARTICIPANTS The sample was 23.8 % female , mean age was 38 , mean years of drug use was 9.4 and 57.8 % had injected drugs in the past 30 days . MEASUREMENTS Treatment retention and negative drug urine . FINDINGS Relative to the treatment-as-usual ( control ) group , better retention was observed among the incentive group in Kunming ( 75 % versus 44 % ) , but no difference was found in Shanghai ( 90 % versus 86 % ) . Su bmi ssion of negative urine sample s was more common among the incentive group than the usual care ( 74 % versus 68 % in Shanghai , 27 % versus 18 % in Kunming ) , as was the longest duration of sustained abstinence ( 7.7 weeks versus 6.5 in Shanghai , 2.5 versus 1.6 in Kunming ) . The average total prize amount was 371 Yuan ( or $ 55 ) per participant ( 527 for Shanghai versus 216 in Kunming ) . CONCLUSIONS Contingency management improves treatment retention and drug abstinence in methadone maintenance treatment clinics in China , although there can be considerable site differences in magnitude of effects Objective . This study was conducted to assess the accuracy of self-reported hepatitis C virus ( HCV ) antibody ( anti-HCV ) serostatus in injection drug users ( IDUs ) , and examine whether self-reported anti-HCV serostatus was associated with recent injection risk behavior . Methods . In five U.S. cities ( Baltimore , Chicago , Los Angeles , New York , and Seattle ) , 3,004 IDUs from 15 to 30 years old were recruited for a baseline interview to determine eligibility for a r and omized controlled trial of a behavioral intervention . HIV and HCV antibody testing were performed , and subject data ( e.g. , demographics , drug and sexual risk behavior , and history of HIV and HCV testing ) were collected via audio computer-administered self-interview . Risk behavior during the previous three months was compared to self-reported anti-HCV serostatus . Results . Anti-HCV prevalence in this sample of young IDUs was 34.1 % . Seventy-two percent of anti-HCV-positive and 46 % of anti-HCV-negative IDUs in this sample were not aware of their HCV serostatus . Drug treatment or needle exchange use was associated with increased awareness of HCV serostatus . Anti-HCV-negative IDUs who knew their serostatus were less likely than those unaware of their status to inject with a syringe used by another IDU or to share cottons to filter drug solutions . Knowledge of one 's positive anti-HCV status was not associated with safer injection practice s. Conclusions . Few anti-HCV-positive IDUs in this study were aware of their serostatus . Exp and ed availability of HCV screening with high quality counseling is clearly needed for this population to promote the health of chronically HCV-infected IDUs and to decrease risk among injectors susceptible to acquiring or transmitting HCV Abstract A number of studies have examined HIV risk behaviors in prisoner population s , but relatively few have examined such behaviors in probationer population s. Since probationers have more opportunities to engage in risk behaviors than do prisoners . the potential importance of HIV interventions with probationers becomes readily apparent . This article examines a sample representative of the supervised probationer population in Delaware . The sample respondents received a baseline interview , then were r and omly selected to receive either an enhanced version of NIDA st and ard HIV Intervention or a Focused Intervention based on a cognitive thought-mapping model . Intervention boosters were offered at two follow-up intervals in the following three months , and respondents were reinterviewed at six months . The data at baseline suggest that probationers in Delaware have levels of injection drug use , other serious drug use , and rates of risky sexual behaviors that approach those observed in prison population s. The interventions ' effectiveness in changing attitudes and behaviors at the six-month interview was then examined . The data support the conclusion that brief interventions can significantly impact both drug use and sexual risk behaviors among probationers . However , there do not appear to be significant improvements for those receiving the more intensive Focused Intervention , as compared to those who receive the enhanced St and ard Intervention . Further work will consider what components in programs and characteristics in clients should be considered in selecting the most appropriate interventions for probationers Hepatitis C virus ( HCV ) is hyperendemic among injection drug users ( IDUs ) . However , few scientifically proven interventions to prevent secondary transmission of HCV from infected IDUs to others exist . This report describes the design , feasibility , and baseline characteristics of participants enrolled in the Study to Reduce Intravenous Exposure ( STRIVE ) . STRIVE was a multisite , r and omized-control trial to test a behavioral intervention developed to reduce distribution of used injection equipment ( needles , cookers , cottons , and rinse water ) and increase health-care utilization among antibody HCV ( anti-HCV ) positive IDUs . STRIVE enrolled anti-HCV positive IDU in Baltimore , New York City , and Seattle ; participants completed behavioral assessment s and venipuncture for HIV , HCV-RNA , and liver function tests ( LFTs ) and were r and omized to attend either a six-session , small-group , peer-mentoring intervention workshop or a time-matched , attention-control condition . Follow-up visits were conducted at 3 and 6 months . At baseline , of the 630 HCV-positive IDUs enrolled ( mean age of 26 years , 60 % white , 76 % male ) , 55 % reported distributive needle sharing , whereas 74 , 69 , and 69 % reported sharing cookers , cottons , and rinse water , respectively . Health-care access was low , with 41 % reporting an emergency room as their main source of medical care . Among those enrolled , 66 % ( 418/630 ) were r and omized : 53 % ( 222/418 ) and 47 % ( 196/418 ) to the intervention and control conditions , respectively . Follow-up rates were 70 and 73 % for the 3- and 6-month visits , respectively . As distributive sharing of used injection equipment was common while reports of receiving HCV care were low , these findings indicate an urgent need for HCV-related interventions with IDUs and demonstrate the acceptability and feasibility to do so AIM To develop and evaluate a brief intervention for reducing risk behaviours associated with HCV transmission in injecting drug users ( IDU ) . DESIGN R and omized controlled trial of an individually tailored brief behavioural intervention ( BBI ) ( experimental ) versus a st and ardized educational intervention ( control ) . SETTING Specialist drug treatment facility in Melbourne , Australia . PARTICIPANTS One hundred and forty-five IDU ( aged 18 or over , injecting at least weekly in the preceding 6 months ) recruited and r and omized to the experimental condition ( n = 73 ) or the control condition ( n = 72 ) . INTERVENTIONS The BBI was based on the Blood-Borne Virus Transmission Risk Assessment Question naire (BBV-TRAQ)-a st and ardized blood-borne virus risk assessment instrument comprising injecting risk , sexual risk and other skin penetration risk subscales . The BBV-TRAQ was used to identify individual HCV risk practice s and to tailor the 30-minute experimental BBI . Control participants received a st and ardized HCV educational session , using current educational material s. MAIN OUTCOME MEASURES BBV-TRAQ subscale and total scores and measures of participant satisfaction . RESULTS One hundred and twenty-four participants ( 86 % ) were followed-up at 4 weeks ( + /-7 days ) . Analyses revealed a significant reduction in HCV risk behaviours for both groups at 1-month follow-up , with participants in the experimental BBI condition reporting higher overall satisfaction with the intervention compared to the control group . CONCLUSIONS Both groups reported significant reductions in risk behaviour , indicating that while BBI methods hold promise for HCV education and prevention , they were not demonstrated to be more effective than the provision of st and ard educational material s. Future research could evaluate the efficacy of the BBV-TRAQ as a risk behaviour intervention and counselling tool in clinical , NSP and peer education setting AIMS This study conducted a secondary analysis to examine injection cessation and decreasing frequency of injection during a multi-site r and omized controlled HIV prevention intervention trial that sought to reduce sexual and injection risk behavior among young injection drug users . DESIGN AND SETTING A six-session , cognitive-behavioral skills-building intervention in which participants were taught peer education skills [ peer education intervention ( PEI ) ] was compared with a time-equivalent attention control . Follow-up interviews were conducted at 3 and 6 months post-baseline . PARTICIPANTS Trial participants were HIV and hepatitis C virus ( HCV ) antibody-negative injection drug users aged 15 - 30 years . Participants who had at least one follow-up interview and reported injecting drugs in the previous 3 months at baseline were eligible for the present analysis ( n = 690 ) . MEASUREMENTS At each interview , data were collected on the number of times participants injected drugs over the previous 3 months . FINDINGS Twenty-seven per cent of participants reported at least one 3-month period of injection cessation . In a multivariate , zero-inflated negative binomial regression adjusting for prior injection frequency , time of follow-up and psychosocial variables , PEI trial arm and smaller session size were associated significantly with injection cessation . Trial arm had no effect on the frequency of injection among those who continued to inject . CONCLUSIONS HIV prevention interventions that encourage injection drug users to take on the role of peer educator may have the additional benefit of increasing the likelihood of injection cessation . Intervention group size is also an important consideration , with smaller groups having higher rates of cessation BACKGROUND To test the initial feasibility of a novel 22-week comprehensive intervention pairing behavioral treatment with naltrexone that aim ed at engaging , retaining , and treating opioid-injecting men in the Republic of Georgia . METHODS Forty opioid-injecting male and their drug-free female partners participated in a two-group r and omized clinical trial at the field site of the Union Alternative Georgia , in Tbilisi , Republic of Georgia . The comprehensive intervention that paired behavioral treatment with naltrexone for the male participants ( n=20 ) included counseling sessions using Motivational Interviewing for both the male participant and the couple , monetary incentives for drug abstinence , and research -supported detoxification followed by naltrexone treatment . Male participants in the usual care condition ( n=20 ) had the opportunity to attend once-a-week individualized education sessions and upon request receive referrals to detoxification programs and aftercare that could or could not have included naltrexone . Outcome measures included entry into inpatient detoxification and naltrexone treatment , urine drug screening , reduction in illicit substance use , use of benzodiazepines , injection of buprenorphine , and needle and syringe sharing . RESULTS The comprehensive intervention condition showed significantly more weekly urine sample s negative for illicit opioids during weeks 1 - 22 ( 7.0 vs. 1.4 ; p<.001 ) and reported significant declines in use of benzodiazepines and injection of buprenorphine ( both ps<.004 ) . CONCLUSIONS The first behavioral treatment r and omized clinical trial in the Republic of Georgia found that the use of tailored behavioral therapy paired with naltrexone is both feasible and efficacious for treating drug use and reducing HIV drug-risk behavior in Georgian men Objective : The objective of this study was to evaluate counseling efficacy among high-risk groups . Study : We conducted a subset analysis of data collected from July 1993 through September 1996 during a r and omized , controlled trial ( Project RESPECT ) . Participants ( n = 4328 ) from 5 public U.S. sexually transmitted disease ( STD ) clinics were assigned to enhanced counseling , brief counseling , or educational messages . For 9 subgroups ( sex , age , city , education , prior HIV test , STD at enrollment , race/ethnicity , injection drug use , exchanging sex for money/drugs ) , we compared STD outcomes for those assigned either type of counseling with STD outcomes for those assigned educational messages . Results : After 12 months , all subgroups assigned counseling ( brief or enhanced ) had fewer STDs than those assigned educational messages . STD incidence was similar for most subgroups assigned enhanced or brief counseling . All subgroups had an appreciable number of STDs prevented per 100 persons counseled , especially adolescents ( 9.4 per 100 ) and persons with STD at enrollment ( 8.4 per 100 ) . Conclusions : HIV/STD prevention counseling ( brief or enhanced counseling ) result ed in fewer STDs than educational messages for all subgroups of STD clinic clients , including high-risk groups such as adolescents and persons with STDs at enrollment This study examined factors associated with methadone maintenance retention , defined as remaining in treatment for a minimum of 90 days , among street recruited injection drug users ( IDUs ) . Targeted sampling methods were used to establish recruitment quotas in Denver census tracks . A total of 577 IDUs were r and omly assigned to either a risk reduction intervention , focusing on safer injection and sex behaviors , or motivational interviewing , addressing more sweeping lifestyle changes including drug treatment . All subjects who wanted treatment were provided transportation , rapid intake and a waiver of the intake fee . In addition , 50 % were r and omly assigned a coupon for 90 days of free treatment . Overall , 33 % entered treatment and of these , 60 % remained for at least 90 days . Factors associated with retention included higher methadone dose , free treatment , greater contacts with the clinic and counselor rating of patient cooperation . Although desire for treatment , or motivation , was associated in univariate analyses with greater retention , there were no differences observed between the motivational interviewing and risk reduction interventions This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors . Participants were r and omized to : ( a ) a two-session , HIV/HCV counseling and education ( C&E ) model added to treatment as usual ( TAU ) , ( b ) a one-session , therapeutic alliance ( TA ) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU , or ( c ) TAU . Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period . C&E participants reported significantly greater rates of attending an HIV testing appointment , but this was not associated with better risk reduction outcomes . Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors . Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months ; interventions added to st and ard treatment offered no improvement in risk behavior outcomes Approximately 36 % of HIV cases are related to substance abuse . Substance abusers , including non-injection drug users , are at a high-risk for contracting HIV due to risky behaviors , including unprotected sex . Due to these behavioral and infection risks , feasible interventions that focus on condom use within this population are imperative . The current study involved the development of brief intervention design ed to increase implementation intentions ( situation-linked action plans ) to use condoms in convicted non-violent drug offenders participating in drug diversion programs in Southern California . Participants ( n = 143 ) were r and omized at the individual level to either waitlist control or experimental conditions . The r and omized waitlist control group received the HIV survey for the pre-test before the intervention , while the experimental group received a neutral , non-HIV-related , survey at pre-test . The experimental group received the HIV survey as the post-test after the intervention ( waitlist control group received the neutral , non-HIV-related , survey ) . One-tailed Mann Whitney U tests were used to compare the waitlist control and experimental groups . The experimental group was more likely to report stronger implementation intentions to use condoms ( p < 0.001 ) . These results indicate in the short term that a brief , easily disseminated HIV intervention can be effective for increasing implementation intentions to use condoms in an extremely high HIV-risk population This study of 577 out-of-treatment drug injectors was design ed to assess predictors of methadone maintenance treatment entry , including offering free treatment coupons . Using targeted sampling methods , participants were recruited through street outreach ; r and omly , they were either assigned a coupon for 90 days of free treatment or required to pay for their treatment . Regardless of assignment , all subjects who desired treatment were provided transportation , rapid intake , and a waiver of the treatment entry fee . Overall , 33 % entered treatment , including 66 % of those who received a free coupon . Other factors associated with treatment entry included desire for treatment , heroin use , prior treatment experience , associating with fewer drug-using friends , and injecting with a previously used unsterile needle/syringe . Injecting cocaine and smoking crack reduced the probability of treatment entry . Findings lend support to street outreach efforts design ed to increase rates of treatment entry among chronic out-of-treatment drug injectors . Additional treatment options are required for those abusing cocaine The aim of this study was to evaluate the efficacy of a theory-based intervention to increase the use of a new syringe for each injection among injection drug users ( IDUs ) . Users of two needle exchange programs ( NEPs ) were involved . At both sites , participants were assigned at r and om to either the experimental or the control group . Once a week for four weeks , users reported to the NEPs where they logged onto a computer and received an audiovisual message . A total of 260 IDUs were recruited . At baseline , 52.3 % of participants reported that they had not always used new syringes in the previous week . The results indicate that it is possible for IDUs to adopt safer injection practice s. One month after the intervention began , participants in the experimental group were using fewer dirty syringes compared to the control group ( RR : 0.47 CI95 % 0.28–0.79 ; P = .004 ) . This short-term effect was no longer present 3 months later BACKGROUND Hepatitis B vaccine provides a model for improving uptake and completion of multidose vaccinations in the drug-using community . METHODS The Drugs , AIDS , STDs , and Hepatitis ( DASH ) project conducted a r and omized controlled trial among not-in-treatment current drug users in 2 urban neighborhoods . Neighborhoods were cluster-r and omized to receive a st and ard behavioral intervention ( which provided information on human immunodeficiency virus [ HIV ] ) or an enhanced behavioral intervention ( design ed to increase acceptance of or adherence to the hepatitis B vaccination protocol ) . Participants within clusters were r and omized to a st and ard vaccination schedule ( vaccines at 0 , 1 , and 6 months ) or an accelerated vaccination schedule ( vaccines at 0 , 1 , and 2 months ) . The outcomes were completion of the 3-dose vaccine and seroprotection against hepatitis B virus ( HBV ) . RESULTS Of participants with negative screening results for HIV and HBV , 77 % accepted hepatitis B vaccination , and 75 % of vaccinees received all 3 doses . Injection drug users ( IDUs ) on the accelerated schedule were significantly more likely to receive 3 doses ( 76 % ) than those on the st and ard schedule ( 66 % ; P = .04 ) , although for drug users as a whole the corresponding adherence rates were 77 % and 73 % , respectively . No difference in adherence was observed between the behavioral intervention groups . Predictors of adherence were older age , African American race , stable housing , and alcohol use . Cumulative HBV seroprotection ( ≥10 mIU/mL ) was gained within 12 months by 65 % of those completing the schedule . Seroprotection at 6 months was greater for those on the accelerated schedule . CONCLUSION The accelerated vaccination schedule improves hepatitis B vaccination adherence among IDUs BACKGROUND The high rates of HIV and Hepatitis C ( HCV ) infection among opioid abusers is a serious public health problem , and efforts to enhance knowledge regarding risks for HIV/hepatitis infection in this population are important . Abuse of prescription opioids ( POs ) , in particular , has increased substantially in the past decade and is associated with increasing rates of injection drug use and HCV infection . METHODS This study describes the effects of a brief HIV/HCV educational intervention delivered in the context of a larger r and omized , double-blind clinical trial evaluating the relative efficacy of 1- , 2- , and 4-week outpatient buprenorphine tapers and subsequent oral naltrexone maintenance for treating PO dependence . HIV- and HCV-related knowledge and risk behaviors were characterized pre- and post-intervention in 54 primary PO abusers . RESULTS The educational intervention was associated with significant improvements in HIV ( p<.001 ) and HCV ( p<.001 ) knowledge . Significant improvements ( p<.001 ) were observed on all three domains of the HIV question naire ( i.e. , general knowledge , sexual risk behaviors , drug risk behaviors ) and on 21 and 11 individual items on the HIV and HCV question naires , respectively . Self-reported likelihood of using a condom also increased significantly ( p<.05 ) from pre- to post-intervention . No additional changes in self-reported risk behaviors were observed . CONCLUSION These results suggest that a brief , easy-to-administer intervention is associated with substantial gains in HIV and HCV knowledge among PO abusers and represents the necessary first step toward the dissemination of a structured prevention HIV and HCV intervention for PO abusers Background . In order to prevent the spread of the hepatitis C virus ( HCV ) amongst Hispanic injection drug users ( IDUs ) , we developed , vali date d , and implemented a multimedia educational intervention program . Methods . A pre-post intervention study design was used to evaluate long-lasting knowledge and behavior changes in a group of 88 low-income Hispanic HIV-infected IDUs . Pre-intervention data was compared with data measured six months after the intervention . Results . A significant increase in the awareness regarding HCV clinical manifestations , HCV risky behaviors , HCV prevention practice s , and HIV/HCV co-infection synergisms was observed in the group six months post-intervention . Conclusion . Our study confirms the long-lasting benefits of multimedia based intervention programs for disseminating HCV prevention strategies in IDUs . Preventive educational approaches that use images , figures , and animations tools can be recommended to target and tailor interventions for vulnerable population BACKGROUND New injection drug users ( IDUs ) are at high risk for blood-borne viral infections . Given U.S. policy to only fund proven-effective HIV prevention interventions , insights into conducting intervention trials among young IDUs are provided here by describing methods and participants ' characteristics in the CIDUS III/DUIT study . METHODS In 2002 - 2004 , 15 - 30-year-old IDUs in Baltimore , Chicago , Los Angeles , New York , and Seattle were recruited through community outreach , advertising and coupon-based participant referrals . Baseline interviews assessed sociodemographics , injection , and sexual behaviors . Antibody tests for HIV and hepatitis A , B , and C viruses ( HAV , HBV , and HCV ) were conducted . IDUs who were HIV and HCV antibody negative at baseline were eligible to participate in a r and omized controlled HIV/HCV prevention trial . Follow-up assessment s were conducted 3 and 6 months post-intervention . Data were analyzed to identify participant differences at baseline by city , trial enrollment , and trial retention . RESULTS Baseline assessment s were completed by 3285 IDUs . Participants were mean age 23.8 years , 69 % male , 64 % White , 17 % Hispanic , and 8 % Black . Seroprevalence of HIV , HCV , HBV , and HAV antibodies were 2.9 , 34.4 , 22.4 , and 19.3 % , respectively . Of the 2062 ( 62.7 % ) baseline participants who were HIV and HCV antibody negative , 859 ( 41.7 % ) were r and omized . At least one follow-up assessment was completed by 712 ( 83 % ) r and omized participants . Context ual factors , primarily homelessness , were associated with lower enrollment and retention . CONCLUSIONS Recruitment and retention of young-adult IDUs for complex intervention trials is complicated , yet feasible . Risk behaviors among participants enrolling in and completing the trial reflected those eligible to enroll Objectives : To evaluate whether a behavioral intervention , which taught peer education skills , could reduce injection and sexual risk behaviors associated with primary HIV and hepatitis C virus infection ( HCV ) among young injection drug users ( IDU ) . Design : We conducted a r and omized controlled trial involving HIV and HCV antibody-negative IDU , aged 15–30 years , recruited in five United States cities . A six-session , small-group , cognitive behavioral , skills-building intervention in which participants were taught peer education skills ( n = 431 ) was compared with a time-equivalent attention control ( n = 423 ) . Baseline visits included interviews for sociodemographic , psychosocial , and behavioral factors during the previous 3 months ; HIV and HCV antibody testing ; and pre/posttest counselling . Procedures were repeated 3 and 6 months postintervention . Results : The intervention produced a 29 % greater decline in overall injection risk 6 months postintervention relative to the control [ proportional odds ratio 0.71 ; 95 % confidence limit ( CL ) 0.52 , 0.97 ] , and a 76 % decrease compared with baseline . Decreases were also observed for sexual risk behaviors , but they did not differ by trial arm . Overall HCV infection incidence ( 18.4/100 person-years ) did not differ significantly across trial arms ( relative risk 1.15 ; 95 % CL 0.72 , 1.82 ) . No HIV seroconversions were observed . Conclusion : Interventions providing information , enhancing risk-reduction skills , and motivating behavior change through peer education training can reduce injection risk behaviors , although risk elimination might be necessary to prevent HCV transmission This study examined the effectiveness of a combined counseling and case management behavioral intervention , using motivational interviewing strategies , in engaging Hispanic injection drug users in treatment and reducing drug use and injection-related HIV risk behaviors . Follow up data are presented on 440 ( 79.0 % ) of 557 r and omized participants , 6 months after the initial interview . Subjects in the experimental arm were significantly less likely to continue drug injection independent of entering drug treatment , and were also more likely to enter drug treatment . Subjects in both arms who entered drug treatment were less likely to continue drug injection . Among subjects who continued drug injection , those in the experimental arm were significantly less likely to share needles . Confirming the outcomes of this study in other Hispanic sites and population s could be a critical step towards reducing factors that contribute to the self-sustaining HIV/AIDS epidemic in Puerto Rico and communities in the U.S. mainl and BACKGROUND Although methadone maintenance is an effective therapy for heroin dependence , some patients continue to use heroin and may benefit from therapeutic modifications . This study evaluated a behavioral intervention , a pharmacological intervention , and a combination of both interventions . METHODS Throughout the study all patients received daily methadone hydrochloride maintenance ( initially 50 mg/d orally ) and weekly counseling . Following baseline treatment patients who continued to use heroin were r and omly assigned to 1 of 4 interventions : ( 1 ) contingent vouchers for opiate-negative urine specimens ( n = 29 patients ) ; ( 2 ) methadone hydrochloride dose increase to 70 mg/d ( n = 31 patients ) ; ( 3 ) combined contingent vouchers and methadone dose increase ( n = 32 patients ) ; and ( 4 ) neither intervention ( comparison st and ard ; n = 28 patients ) . Methadone dose increases were double blind . Vouchers had monetary value and were exchangeable for goods and services . Groups not receiving contingent vouchers received matching vouchers independent of urine test results . Primary outcome measure was opiate-negative urine specimens ( thrice weekly urinalysis ) . RESULTS Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention . Contingent vouchers , with or without a methadone dose increase , increased the duration of sustained abstinence as assessed by urine screenings . Methadone dose increase , with or without contingent vouchers , reduced self-reported frequency of use and self-reported craving . CONCLUSIONS In patients enrolled in a methadone-maintainence program who continued to use heroin , abstinence reinforcement and a methadone dose increase were each effective in reducing use . When combined , they did not dramatically enhance each other 's effects on any 1 outcome measure , but they did seem to have complementary benefits ABSTRACT To test whether a four-session motivational intervention would reduce hepatitis C virus ( HCV ) seroincidence among injection and non-injection drug users compared to an assessment -only condition , we performed a r and omized 24-month clinical trial . At baseline , 277 participants reported using heroin or cocaine at least three times weekly were HCV antibody negative , 65 % were male and 46 % were Caucasian and 39 % reported having injected drugs . Of the 15 ( 5.4 % ) individuals who seroconverted , all reported injecting drugs either at baseline or during follow-up . Seroconversion rates did not differ significantly by treatment assignment ( p = .79 ) . The annual HCV incident rate was 8.20 ( 95 % confidence interval [ CI ] = 4.76–14.13 ) for injectors and 0.74 ( 95 % CI = 0.19–2.98 ) for non-injectors per 100 person-years . Significantly fewer participants in the intervention group initiated injection drug use behaviors ( p = .009 ) . This intervention was no more effective at reducing HCV seroconversion than assessment alone but did decrease injection initiation This paper presents the results of a study evaluating the efficacy of a theory-based cognitive – behavioral intervention to reduce HIV risk among street-based crack and injection drug users not currently in drug treatment in Long Beach , California . A nine-session , 4-month enhanced intervention ( including HIV counseling and testing ) was compared to a two-session st and ard counseling and testing intervention developed by the National Institute on Drug Abuse ( NIDA ) in terms of their efficacy for reducing drug- and sex-related risk behaviors . The theory-based enhanced intervention rarely was found to be different from NIDA 's st and ard counseling and testing intervention in reducing both drug- and sex-related risks , as indicated by cessation and /or reduction of drug use ( measured by urine test and self-report ) , entry into drug treatment , and increased frequency of condom use . One of the few significant effects was that the enhanced intervention significantly increased injecting drug users ' use of their own injection equipment . On the other h and , for both interventions , most risk behaviors were significantly reduced . It is concluded that the theory-based cognitive – behavioral intervention has limited advantage over the st and ard intervention in terms of both magnitude and frequency of HIV risk reduction achieved by high-risk , active drug users This pilot r and omized controlled trial in Kazakhstan aim ed to adapt and test the feasibility of a couple-based HIV/STI risk-reduction intervention ( CHSR ) for couples who are injecting drug users ( IDUs ) . The study examined the preliminary effects of the intervention versus an attentional control wellness promotion ( WP ) condition on HIV risk behavioral outcomes among 40 couples who are IDUs ( n = 80 participants ) . Compared with WP participants , CHSR participants were significantly more likely to increase condom use and decrease unsafe injection acts at the 3-month follow-up . This pilot trial demonstrates the feasibility and preliminary effects of the CHSR in reducing drug-related and sexual HIV risks A network-oriented HIV prevention intervention based on social identity theory and peer outreach was implemented for HIV positive and negative drug users . A community sample of 250 were r and omly assigned to an equal-attention control condition or a multisession , small-group experimental condition , which encouraged peer outreach ; 94 % of participants were African American , and 66 % used cocaine or opiates . At follow-up , 92 % of participants returned , and experimental compared with control group participants were 3 times more likely to report reduction of injection risk behaviors and 4 times more likely to report increased condom use with casual sex partners . Results suggest that psychosocial intervention emphasizing prosocial roles and social identity , and incorporating peer outreach strategies , can reduce HIV risk in low-income , drug-using communities Globally , 30 % of new HIV infections outside sub-Saharan Africa involve injecting drug users ( IDU ) and in many countries , including Vietnam , HIV epidemics are concentrated among IDU . We conducted a r and omized controlled trial in Thai Nguyen , Vietnam , to evaluate whether a peer oriented behavioral intervention could reduce injecting and sexual HIV risk behaviors among IDU and their network members . 419 HIV-negative index IDU aged 18 years or older and 516 injecting and sexual network members were enrolled . Each index participant was r and omly assigned to receive a series of six small group peer educator-training sessions and three booster sessions in addition to HIV testing and counseling ( HTC ) ( intervention ; n = 210 ) or HTC only ( control ; n = 209 ) . Follow-up , including HTC , was conducted at 3 , 6 , 9 and 12 months post-intervention . The proportion of unprotected sex dropped significantly from 49 % to 27 % ( SE ( difference ) = 3 % , p < 0.01 ) between baseline and the 3-month visit among all index-network member pairs . However , at 12 months , post-intervention , intervention participants had a 14 % greater decline in unprotected sex relative to control participants ( Wald test = 10.8 , df = 4 , p = 0.03 ) . This intervention effect is explained by trial participants assigned to the control arm who missed at least one st and ardized HTC session during follow-up and subsequently reported increased unprotected sex . The proportion of observed needle/syringe sharing dropped significantly between baseline and the 3-month visit ( 14 % vs. 3 % , SE ( difference ) = 2 % , p < 0.01 ) and persisted until 12 months , but there was no difference across trial arms ( Wald test = 3.74 , df = 3 , p = 0.44 ) Objective : To determine if , by reducing depressive symptoms , combined psychotherapy and pharmacotherapy reduces HIV drug risk behavior compared to an assessment -only condition for active drug injectors over 9 months . Design : R and omized controlled trial . Setting : Outpatient academic research office . Patients : Active injection drug users with a DSM-IV diagnosis of major depression , dysthymia , substance-induced mood disorder with depressive features persisting for at least 3 months , or major depression plus dysthymia . In addition , participants had a Hamilton Rating Scale for Depression ( MHRSD ) score > 13 . Intervention : Psychotherapy ( 8 sessions of cognitive behavioral therapy ) plus antidepressant pharmacotherapy over 3 months . Main Outcome Measures : HIV Risk Assessment Battery ( RAB ) drug scale scores measured at three , six and nine months , and depression remission ( MHRSD score ≤ 8) . Results : Participants ( n = 109 ) were 64 % male , 82 % Caucasian , with a mean baseline MHRSD score of 20.7 . Depression subtypes included major depression only ( 63 % ) , substance-induced depression ( 17 % ) , and double-depression ( 17 % ) . Overall , study retention at nine months was 89 % . Reported HIV drug risk scores decreased sharply over the first 3 months and continued to decline throughout the follow-up period . Between group differences were not significant in the intention-to-treat analysis . However , highly adherent participants had significantly lower HIV drug risk scores at 3 months ( p < 05 ) , but not 6 and 9 months . Depression remission was significantly associated with lower HIV drug risk scores at follow-ups . Conclusions : Combined psychotherapy and pharmacotherapy did not produce a significant reduction in HIV drug risk beyond that seen in an assessment -only control group . The greatest declines in HIV drug risk were found in participants with high protocol adherence and those with depression remission Background Female sex workers who inject drugs ( FSW-IDUs ) are at risk of acquiring HIV , sexually transmitted infections ( STI ) and blood-borne infections through unprotected sex and sharing injection equipment . We conducted a 2 × 2 factorial r and omized controlled trial to evaluate combination interventions to simultaneously reduce sexual and injection risks among FSW-IDUs in Tijuana and Ciudad Juarez , Mexico . Methods / design FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month were r and omized to one of four conditions based on an a priori r and omization schedule , blinding interviewer/counselors to assignment . Due to the extreme vulnerability of this population , we did not include a control group that would deny some women access to preventive information . All women received similar information regardless of group allocation ; the difference was in the way the information was delivered and the extent to which women had an interactive role . Each condition was a single 60-minute session , including either an interactive or didactic version of an injection risk intervention and sexual risk intervention . Women underwent interviewer-administered surveys and testing for HIV , syphilis , gonorrhea , Chlamydia , and Trichomonas at baseline and quarterly for 12 months . Combined HIV/STI incidence will be the primary outcome . Secondary outcomes are proportionate reductions in sharing of injection equipment and unprotected sex with clients . Discussion Of 1,132 women , 548 ( 48.4 % ) were excluded ( 88.9 % were ineligible ; 11.1 % refused to participate or did not return ) ; 584 eligible women enrolled ( 284 in Tijuana ; 300 in Ciudad Juarez ) . All 584 participants completed the baseline interview , provided biological sample s and were r and omized to one of the four groups . During follow-up , 17 participants ( 2.9 % ) were lost to follow-up , of whom 10 ( 58.8 % ) had died , leaving 567 participants for analysis . This study appears to be the first intervention to attempt to simultaneously reduce injection and sexual risk behaviors among FSW-IDUs . The factorial design will permit analysis to determine whether the combination of the two interactive interventions and /or its respective components are effective in reducing injection and /or sexual risks , which will have direct , tangible policy implication s for Mexico and potentially other re source -poor countries . Trial registration Objective : Dual threats of injection drug use and risky sexual practice s continue to increase transmission of HIV and other sexually transmitted Infections ( STIs ) among drug-using couples in low-income communities in the United States . Two hypotheses were tested : ( 1 ) “ intervention effect”—whether the HIV risk-reduction intervention provided to the couple or individual partners would be more efficacious in decreasing number of unprotected sexual acts and having a lower cumulative incidence of biologically confirmed STIs over the 12-month follow-up period compared with the attention control condition ; and ( 2 ) “ modality effect”—whether the HIV risk-reduction intervention would be more likely to decrease the number of unprotected sexual acts and have a lower cumulative STI incidence when delivered to a couple compared with the same intervention delivered to an individual . Design : Using a r and omized controlled trial , 282 HIV-negative drug-using couples ( 564 individuals ) were r and omly assigned to receive either of the following : ( 1 ) couple-based risk reduction ; ( 2 ) individual-based HIV risk reduction , or ( 3 ) couple-based wellness promotion , which served as an attention control condition . Results : Over 12-month follow-up , there was a 30 % reduction in the incidence rate of unprotected acts of intercourse with the study partners compared with participants in the attention control arm . Moreover , over 12-month follow-up there was a 29 % reduction in the same outcome in the couple arm compared with the individual arm with a 41 % reduction at the 12-month follow-up . Conclusion : A couple-based approach that addresses drug and sexual risks and targets low-income active drug users may help curb the HIV epidemic AIMS This study assessed the effectiveness of HERMITAGE ( HIV 's Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic ) , an adapted secondary HIV prevention intervention , compared with an attention control condition in decreasing sexually transmitted infections ( STIs ) and sex and drug risk behaviors among Russian HIV-infected heavy drinkers . DESIGN We conducted a single-blinded , two-armed , r and omized controlled trial with 12-month follow-up . SETTING The study was conducted in St Petersburg , Russia . Participants were recruited from four HIV and addiction clinical sites . The intervention was conducted at Botkin Infectious Disease Hospital . PARTICIPANTS HIV-infected individuals with past 6-month risky sex and heavy alcohol consumption ( n = 700 ) were r and omized to the HERMITAGE intervention ( n = 350 ) or an attention control condition ( n = 350 ) . INTERVENTION A Healthy Relationships Intervention stressing disclosure of HIV serostatus and condom use , adapted for a Russian clinical setting with two individual sessions and three small group sessions . MEASUREMENTS The primary outcome was incident STI by laboratory test at 12-month follow-up . Secondary outcomes included change in unprotected sex and several alcohol and injection drug use ( IDU ) variables . FINDINGS Participants had the following baseline characteristics : 59.3 % male , mean age 30.1 , 60.4 % past year IDU , 15.4 % prevalent STI and mean CD4 cell count 413.3/μl . Assessment occurred among 75 and 71 % of participants at 6 and 12 months , respectively . STIs occurred in 20 subjects ( 8.1 % ) in the intervention group and 28 subjects ( 12.0 % ) in the control group at 12-month follow-up ; logistic regression analyses found no significant difference between groups ( adjusted odds ratio 0.63 ; 95 % confidence interval = 0.34 - 1.18 ; P = 0.15 ) . Both groups decreased unsafe behaviors , although no significant differences were found between groups . CONCLUSIONS The HERMITAGE HIV risk reduction intervention does not appear to reduce sexually transmitted infections and HIV risk behaviors in Russian HIV-infected heavy drinkers compared with attention controls |
2,363 | 29,944,076 | The major findings of this review can be described as follows : ( a ) HRVBF and psychological stress in peripartum women are related concepts , ( b ) peripartum women who completed HRVBF report a reduction in stress compared with participants who did not receive HRVBF , and ( c ) there is currently no information on the effectiveness of HRVBF on psychological stress in the first and early second trimester of pregnancy .
Overall , this systematic review of the literature provides objective evidence that HRVBF may be a potential beneficial adjuvant treatment for stress management in peripartum women | Peripartum women are exposed to a variety of stressors that have adverse health consequences for the maternal – child dyad ( e.g. , impaired bonding ) .
To combat these adverse health consequences , heart rate variability biofeedback ( HRVBF ) may be implemented by holistic nurses to aid peripartum women experiencing a high level of stress . | BACKGROUND It is unclear from prior reports whether the relationships between self-ratings of anxiety or emotional stress and parasympathetic nervous system components of heart rate variability are independent of personality and cardiorespiratory fitness . We examined those relationships in a clinical setting prior to a st and ardized exercise test . METHODS AND RESULTS Heart rate variability ( HRV ) was measured during 5 min of supine rest among 92 healthy men ( N=52 ) and women ( N=40 ) who had above-average cardiorespiratory fitness as indicated by peak oxygen uptake measured during grade -incremented treadmill exercise . HRV data sets were decomposed into low-frequency ( LF ; 0.05 - 0.15 Hz ) and high-frequency ( HF ; 0.15 - 0.5 Hz ) components using spectral analysis . Self-ratings of trait anxiety and perceived emotional stress during the past week were also assessed . CONCLUSIONS There was an inverse relationship between perceived emotional stress during the past week and the normalized HF component of HRV ( P=0.038 ) . This indicates a lower cardiac vagal component of HRV among men and women who perceived more stress . That relationship was independent of age , gender , trait anxiety , and cardiorespiratory fitness . It was also independent of heart rate ; mean arterial blood pressure ; and respiration rate , factors which can influence HRV and might be elevated among people reporting anxiety and perceived stress . We conclude that vagal modulation of heart period appears to be sensitive to the recent experience of persistent emotional stress , regardless of a person 's level of physical fitness and disposition toward experiencing anxiety In a study of the effectiveness of systematic relaxation training alone or combined with biofeedback in the treatment of hypertension in pregnancy , 60 women were seen weekly for 6 weeks . 18 were given relaxation therapy alone ( group A ) , 18 relaxation plus biofeedback ( group B ) , and there were 24 controls . Whereas two-thirds of the control group had to be admitted to hospital during their pregnancies , less than a third of each experimental group had to be admitted . The experimental groups also had significantly lower systolic and diastolic blood pressure than the control group . There were no significant differences between groups A and B in hospital admission rates or blood-pressure measurements Matched groups of primigravid women received one of three antenatal training programmes : normal antenatal classes , normal classes plus electromyography biofeedback relaxation training , or normal classes plus skin-conductance biofeedback relaxation training . Myographic training was found to be effective within conventional antenatal constraints , whereas skin-conductance training was not . The women reported use of biofeedback training and related skills to be of some benefit during early labour . However , no difference between effectively trained electromyographic , ineffectively trained skin-conductance and control groups was found on labour and delivery performance measures OBJECTIVE Prenatal distress has been linked to pregnancy complications and poor offspring 's health , despite the fact that longitudinal assessment s of various stress dimensions are still lacking . Hence , we aim ed to assess perceived stress over the course of pregnancy . Moreover , we examined whether social support and coping styles are linked to prenatal stress trajectories . METHODS Data from 543 women participating in the PRINCE ( Prenatal Identification of Children Health ) study , a prospect i ve population -based cohort study , was used for the present analyses . Once per trimester the women completed question naires regarding different psychometric measures , including the Perceived Stress Scale ( PSS ) . Linear mixed regression models were used to examine perceived stress development longitudinally and to relate social support and coping styles to stress trajectories during pregnancy . RESULTS A significant decrease of perceived stress was observed over the course of pregnancy . Stratifying the study sample according to parity , women delivering their first child had continuously lower perceived stress scores compared to women having already one or more children , and a significant decrease during pregnancy was exclusively observed in primiparous women . Both , positive coping strategies and higher perceived and received social support were independently associated with lower perceived stress , while evasive coping strategies were associated with higher levels of perceived stress . CONCLUSION Our study reveals stress perception trajectories during pregnancies in primi- and multiparous women . Our findings underscore the need for intervention strategies aim ing to improve social support and positive coping strategies especially in multiparous women in order to reduce the risks for adverse pregnancy outcomes Acute psychosocial stress is typically investigated in laboratory setting s using protocol s with distinctive characteristics . For example , some tasks involve the action of speaking , which seems to alter Heart Rate Variability ( HRV ) through acute changes in respiration patterns . However , it is still unknown which task induces the strongest subjective and autonomic stress response . The present cross-over r and omized trial sought to investigate the differences in perceived stress and in linear and non-linear analyses of HRV between three different verbal ( Speech and Stroop ) and non-verbal ( Montreal Imaging Stress Task ; MIST ) stress tasks , in a sample of 60 healthy adults ( 51.7 % females ; mean age = 25.6 ± 3.83 years ) . Analyses were run controlling for respiration rates . Participants reported similar levels of perceived stress across the three tasks . However , MIST induced a stronger cardiovascular response than Speech and Stroop tasks , even after controlling for respiration rates . Finally , women reported higher levels of perceived stress and lower HRV both at rest and in response to acute psychosocial stressors , compared to men . Taken together , our results suggest the presence of gender-related differences during psychophysiological experiments on stress . They also suggest that verbal activity masked the vagal withdrawal through altered respiration patterns imposed by speaking . Therefore , our findings support the use of highly-st and ardized math task , such as MIST , as a valid and reliable alternative to verbal protocol s during laboratory studies on stress A study of the effects of biofeedback on the pain of childbirth was conducted . Forty primigravidae were r and omly assigned to either an experimental group or a control group . The experimental group was given a series of training sessions in biofeedback and used biofeedback equipment during labor . All subjects were monitored during the labor and delivery period for their reports of pain using a visual analogue scale ( VAS ) and a verbal descriptor scale ( VDS ) . Results showed that women using biofeedback during childbirth reported significantly lower pain : from admission to labor and delivery ( p less than 0.05:VDS ; p less than 0.01:VAS ) , at delivery ( p less than 0.005:VDS ) , and 24-hr postpartum ( p less than 0.01:VDS ) . Also , women in the biofeedback group labored an average of 2 hr less and used 30 % fewer medications . The results of this study suggest that EMG biofeedback may be effective in reducing levels of acute pain experienced by childbearing women The aim of this study was to investigate cardiac functional status in pregnancy using a comprehensive approach taking into account the simultaneous changes in loading and geometry , as well as maternal age and anthropometric indices . This was a prospect i ve cross-sectional study of 559 nulliparous pregnant women assessed at 4 time points during pregnancy and at 1 year postpartum . All women underwent conventional echocardiography and tissue Doppler velocities and strain rate analysis at multiple cardiac sites . Mean arterial pressure and total vascular resistance index significantly decreased ( both P<0.001 ) during the first 2 trimesters of pregnancy and increased thereafter . Stroke volume index and cardiac index showed the opposite trend compared with mean arterial pressure and total vascular resistance index ( both P<0.05 ) . Myocardial and ventricular function were significantly enhanced in the first 2 trimesters but progressively declined thereafter . By the end of pregnancy , significant chamber diastolic dysfunction and impaired myocardial relaxation was evident in 17.9 % and 28.4 % of women , respectively , whereas myocardial contractility was preserved . There was full recovery of cardiac function at 1 year postpartum . Cardiovascular changes during pregnancy are thought to represent a physiological adaptation to volume overload . The findings of a drop in stroke volume index , impaired myocardial relaxation with diastolic dysfunction , and a tendency toward eccentric remodeling in a significant proportion of cases at term are suggestive of cardiovascular maladaptation to the volume-overloaded state in some apparently normal pregnancies . These unexpected cardiovascular findings have important implication s for the management of both normal and pathological pregnancy states 1 . The effect of a variation in inspiration and expiration times on heart rate variability was studied in 12 healthy subjects ( mean age 30±6 years ; five females ) This investigation assessed the efficacy of a biobehavioral intervention in the adjunctive treatment of mild pregnancy-induced hypertension ( PIH ) , a potentially serious complication of pregnancy in which normotensive women develop hypertension , proteinuria , and edema of unknown etiology late in gestation . Forty-five women with symptoms of PIH were r and omly assigned to one of three treatment conditions : bed rest alone ( the most common obstetrical treatment ) , bed rest with individualized compliance enhancement training , or a four-session biobehavioral treatment consisting of bed rest , compliance enhancement training , and individualized thermal biofeedback-assisted relaxation training . Results indicated that while blood pressure for the bed rest and compliance enhancement groups continued to rise and pose an increasing health risk to maternal and fetal well-being , subjects in the biobehavioral group maintained their blood pressure at a significantly lower , and presumably safer , level . The biobehavioral treatment is hypothesized to affect blood pressure levels in subjects with mild PIH through the mediation of the sympathetic nervous system , decreasing peripheral vascular resistance and cardiac output . The results of this investigation suggest that the biobehavioral intervention may be an effective adjunct to bed rest in the treatment of mild PIH remote from term PURPOSE This study was conducted to investigate the effectiveness of pelvic floor muscle exercise using biofeedback and electrical stimulation after normal delivery . METHODS The subjects of this study were 49 ( experimental group : 25 , control group : 24 ) postpartum women who passed 6 weeks after normal delivery without complication of pregnancy , delivery and postpartum . The experimental group was applied to the pelvic muscle enforcement program by biofeedback and electrical stimulation for 30 minutes per session , twice a week for 6 weeks , after then self-exercise of pelvic floor muscle was done 50 - 60 repetition per session , 3 times a day for 6 weeks . Maximum pressure of pelvic floor muscle contraction ( MPPFMC ) , average pressure of pelvic floor muscle contraction ( APPFMC ) , duration time of pelvic floor muscle contraction ( DTPFMC ) and the subjective lower urinary symptoms were measured by digital perineometer and Bristol Female Urinary Symptom Question naire and compared between two groups prior to trial , at the end of treatment and 6 weeks after treatment . RESULTS The results of this study indicated that MPPFMC , APPFMC , DTPFMC were significantly increased and subjective lower urinary symptoms were significantly decreased after treatment in the experimental group than in the control group . CONCLUSIONS This study suggested that the pelvic floor muscle exercise using biofeedback and electrical stimulation might be a safer and more effective program for reinforcing pelvic floor muscle after normal delivery BACKGROUND Several parameters of heart rate variability ( HRV ) have been shown to predict the risk of sudden cardiac death ( SCD ) in cardiac patients . There is consensus that risk prediction is increased when measuring HRV during specific provocations such as orthostatic challenge . For the first time , we provide data on reproducibility of such a test in patients with a history of acute coronary syndrome . METHODS Sixty male patients ( 65 ± 8 years ) with a history of acute coronary syndrome on stable medication were included . HRV was measured in supine ( 5 min ) and st and ing ( 5 min ) position on 2 occasions separated by two weeks . For risk assessment relevant time-domain [ st and ard deviation of all R-R intervals ( SDNN ) and root mean squared st and ard differences between adjacent R-R intervals ( RMSSD ) ] , frequency domain [ low-frequency power ( LF ) , high-frequency power ( HF ) and LF/HF power ratio ] and short-term fractal scaling component ( DF1 ) were computed . Absolute reproducibility was assessed with the st and ard errors of the mean ( SEM ) and 95 % limits of r and om variation , and relative reproducibility by the intraclass correlation coefficient ( ICC ) . RESULTS We found comparable SEMs and ICCs in supine position and after an orthostatic challenge test . All ICCs were good to excellent ( ICCs between 0.636 and 0.869 ) . CONCLUSIONS Reproducibility of HRV parameters during orthostatic challenge is good and comparable with supine position Abstract Objective : We sought to characterise the influence of an antenatal exercise programme on ECG-derived cardiac variables . Methods : Fifity-one healthy pregnant women were recruited and r and omly assigned ( 2 × 2 × 2 design ) to an exercise group or a control group . Exercising groups attended weekly classes from the 20th week of pregnancy onwards . Cardiovascular assessment s ( heart rate variabiliy ( HRV ) , QT , and the QT variability index ( QTVI ) ) were performed at 12–16 , 26–28 , 34–36 weeks and 12 weeks following birth , during supine rest and exercise conditions . Results : Advancing gestation was associated with an increased maternal heart rate ( p = 0.001 ) , shorter QT interval ( p = 0.003 ) , diminished HRV ( p = 0.002 ) and increased QTVI ( p = 0.002 ) . Each of these changes was reversed within 12 weeks postpartum ( p < 0.004 ) . The Exercise group displayed exaggerated changes for all variables ( except QT ) but only during supine rest in the third trimester ( p < 0.029 ) . Conclusion : Advancing gestation is associated with a shift in HRV/QTVI towards values that have been associated with an elevated risk of arrhythmia . A 20-week exercise programme undertaken between mid and late pregnancy exaggerated these changes during rest in the third trimester of pregnancy A sizable body of evidence indicates that prenatal maternal stress ( PNMS ) has an adverse impact on birth outcomes , including birth weight and gestational age at delivery . The authors hypothesized that effects of PNMS are attributable in part to dispositions such as pessimism that lead women to view their lives as stressful and that effects of PNMS and disposition on birth outcome are mediated by prenatal health behaviors . Using structural equations modeling procedures , the authors examined prospect i ve impact of PNMS and dispositional optimism on birth weight and gestational age in a medically high-risk sample ( N = 129 ) , controlling for effects of risk and ethnicity . After its strong inverse association with optimism was accounted for , PNMS had no impact on birth outcomes . Women who were least optimistic delivered infants who weighed significantly less , controlling for gestational age . Optimists were more likely to exercise , and exercise was associated with lower risk of preterm delivery . Results suggest that chronic stress in pregnancy may be a reflection of underlying dispositions that contribute to adverse birth outcomes Preterm birth is a highly prevalent phenomenon that was shown to be associated with mental stress during pregnancy ( Rich-Edwards and Grizzard in Am J Obstet Gynecol 192(5 Suppl):S30–S35 , 2005 ) . We aim ed to assess the effects of heart rate variability (HRV)-biofeedback in patients with preterm labour . Therefore , we conducted a controlled r and omized parallel group study in 48 female patients aged 19–38 years ( median = 29 ) with preterm labour at gestational week 24th–32nd ( median = 29th ) . In this study , one group ( n = 24 ) attended six sessions of HRV-biofeedback over 2 weeks whereas patients of the other group ( n = 24 ) were assigned to control sessions . In the HRV-biofeedback treated group , perception of chronic stress was decreased 4 weeks after completion of training compared to baseline ( p < 0.05 ) but there was no change in the control group . In the HRV-biofeedback group , preterm birth was seen in 3 patients ( 13 % ) whereas in the control group , preterm delivery occurred in 8 patients ( 33 % , p = n.s . ) . There was no difference in birth weight between groups and HRV remained unchanged . In conclusion , our study demonstrates that HRV-biofeedback can reduce chronic stress in patients with preterm labour when administered as an adjunct to routine care . However , it remains unclear whether stress reduction through HRV-biofeedback has a beneficial effect on preterm birth In this study respiratory rates of 3 , 4 , 6 , 8 , 10 , 12 , and 14 breaths per minute were employed to investigate the effects of these rates on heart rate variability ( HRV ) . Data were collected 16 times at each respiratory rate on 3 female volunteers , and 12 times on 2 female volunteers . Although mean heart rates did not differ among these respiratory rates , respiratory-induced trough heart rates at 4 and 6 breaths per minute were significantly lower than those at 14 breaths per minute . Slower respiratory rates usually produced higher amplitudes of HRV than did faster respiratory rates . However , the highest amplitudes were at 4 breaths per minute . HRV amplitude decreased at 3 breaths per minute . The results are interpreted as reflecting the possible effects of the slow rate of acetylcholine metabolism and the effect of negative resonance at 3 cycles per minute Little is known about transient effects of foods and nutrients on reactivity to mental stress . In a r and omized crossover study of healthy adults ( n=20 ) , we measured heart rate variability ( respiratory sinus arrhythmia ) , blood pressure , and other hemodynamic variables after three test meals varying in type and amount of fat . Measurements were collected at rest and during speech and cold pressor tasks . There were significant postmeal changes in resting diastolic blood pressure ( -4 % ) , cardiac output ( + 18 % ) , total peripheral resistance ( -17 % ) , and interleukin-6 ( -27 % ) . Heart rate variability and hemodynamic reactivity to stress was not affected by meal content . We recommend that future studies control for time since last meal and continue to examine effects of meal content on heart rate variability |
2,364 | 28,990,665 | There were no significant differences between TENS and placebo for pain at rest .
There was insufficient high- quality evidence to support or refute the use of TENS for fibromyalgia . | BACKGROUND Fibromyalgia is characterised by persistent , widespread pain ; sleep problems ; and fatigue .
Transcutaneous electrical nerve stimulation ( TENS ) is the delivery of pulsed electrical currents across the intact surface of the skin to stimulate peripheral nerves and is used extensively to manage painful conditions .
TENS is inexpensive , safe , and can be self-administered .
TENS reduces pain during movement in some people so it may be a useful adjunct to assist participation in exercise and activities of daily living .
To date , there has been only one systematic review in 2012 which included TENS , amongst other treatments , for fibromyalgia , and the authors concluded that TENS was not effective .
OBJECTIVES To assess the analgesic efficacy and adverse events of TENS alone or added to usual care ( including exercise ) compared with placebo ( sham ) TENS ; no treatment ; exercise alone ; or other treatment including medication , electroacupuncture , warmth therapy , or hydrotherapy for fibromyalgia in adults . | Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion 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 BACKGROUND Fibromyalgia is a chronic pain syndrome associated with sleep disorders , fatigue and psychological symptoms . Combinations therapies , such as electrotherapy and therapeutic exercises have been used in the clinical practice . AIM To assess the efficacy of high-frequency transcutaneous electrical nerve stimulation ( TENS ) as an adjuvant therapy to aerobic and stretching exercises , for the treatment of fibromyalgia . DESIGN Controlled clinical trial . SETTING Unit of rehabilitation of a public hospital . POPULATION Twenty-eight women aged 52.4±7.5 years , with fibromyalgia . METHODS A visual analogue scale measured pain intensity ; tender points pain threshold , by dolorimetry ; and quality of life , by the Fibromyalgia Impact Question naire . All subjects participated in an eight-week program consisting of aerobic exercises , followed by static stretching of muscle chains . In TENS group , high-frequency ( 150 Hz ) was applied on bilateral tender points of trapezium and supraspinatus . RESULTS TENS group had a greater pain reduction ( mean change score=-2.0±2.9 cm ) compared to Without TENS group ( -0.7±3.7 cm ) . There was a difference between mean change scores of each group for pain threshold ( right trapezium : 0.2±1 kg/cm² in TENS group and -0.2±1.2 kg/cm² in Without TENS group ) . In the evaluation of clinical ly important changes , patients receiving TENS had relevant improvement of pain , work performance , fatigue , stiffness , anxiety and depression compared to those not receiving TENS . CONCLUSION It has suggested that high-frequency TENS as an adjuvant therapy is effective in relieving pain , anxiety , fatigue , stiffness , and in improving ability to work of patients with fibromyalgia . CLINICAL REHABILITATION IMPACT High-frequency TENS may be used as a short-term complementary treatment of fibromyalgia UNLABELLED Transcutaneous electrical nerve stimulation ( TENS ) is an electrophysical modality used for pain management . This study investigated the dose response of different TENS intensities on experimentally induced pressure pain . One hundred and thirty TENS naïve healthy individuals ( 18 - 64 years old ; 65 males , 65 females ) were r and omly allocated to 5 groups ( n = 26 per group ) : Strong Non Painful TENS ; Sensory Threshold TENS ; Below Sensory Threshold TENS ; No Current Placebo TENS ; and Transient Placebo TENS . Active TENS ( 80 Hz ) was applied to the forearm for 30 minutes . Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds ( PPT ) were recorded from 2 points on the h and and forearm before and after TENS to measure hypoalgesia . There were significant differences between groups at both the h and and forearm ( ANOVA ; P = .005 and .002 ) . At 30 minutes , there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to : Below Sensory Threshold TENS , No Current Placebo TENS and Transient Placebo TENS groups ( P < .0001 ) at the forearm ; Transient Placebo TENS and No Current Placebo TENS groups at the h and ( P = .001 ) . There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups . The area under the curve for the changes in PPT significantly correlated with the current amplitude ( r(2 ) = .33 , P = .003 ) . These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes . PERSPECTIVE This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect ; thus , we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief Summary Pain and fatigue during movement , but not at rest , are reduced by a onetime 30‐m treatment with active transcutaneous electrical nerve stimulation ( TENS ) in individuals with fibromyalgia . Abstract Because transcutaneous electrical nerve stimulation ( TENS ) works by reducing central excitability and activating central inhibition pathways , we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition . The current study used a double‐blinded r and omized , placebo‐controlled cross‐over design to test the effects of a single treatment of TENS with people with fibromyalgia . Three treatments were assessed in r and om order : active TENS , placebo TENS and no TENS . The following measures were assessed before and after each TENS treatment : pain and fatigue at rest and in movement ; pressure pain thresholds , 6‐m walk test , range of motion ; 5‐time sit‐to‐st and test , and single‐leg stance . Conditioned pain modulation was completed at the end of testing . There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS . Pressure pain thresholds increased at the site of TENS ( spine ) and outside the site of TENS ( leg ) when compared to placebo TENS or no TENS . During active TENS , conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS . No changes in functional tasks were observed with TENS . Thus , the current study suggests TENS has short‐term efficacy in relieving symptoms of fibromyalgia while the stimulator is active . Future clinical trials should examine the effects of repeated daily delivery of TENS , similar to the way in which TENS is used clinical ly on pain , fatigue , function , and quality of life in individuals with fibromyalgia Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Fibromyalgia is characterized by a range of symptoms that include muscle pain , fatigue and sleep disorders . Transcutaneous electrical nerve stimulation ( TENS ) is an established method for pain relief . The purpose of the study was to evaluate the effectiveness and safety of the use of two simultaneously new TENS devices for fibromyalgia pain . After Ethics approval and informed consent , 39 patients were prospect ively divided into three groups to evaluate TENS device , applied simultaneously in each patient : ( 1 ) at the lower back ( perpendicular to the vertebrae canal , at the level of the 5th lumbar vertebrae ) and ( 2 ) central ly above and below the space between the C7 and T1 spinous processes . The devices were applied for 20 min at 12-h interval during 7 consecutive days . For the placebo group ( PG ) , the devices did not transmitted electrical stimulus . The single-TENS group ( STG ) ( n = 13 ) had one active and one placebo TENS . The DTG applied both active TENS devices at the low back and cervical areas . Diclofenac was used as rescue analgesic . The efficacy measures were pain relief , reduction in use of daily analgesic tablets , quality of sleep and fatigue . The evaluation within groups revealed that patients from DPG refereed no pain relief when compared to their previous VAS pain score ( 8 cm , p > 0.05 ) , while patients from the STG refereed improvement of 2.5 cm in the pain VAS ( previous 8.5 cm compared to 6 cm after treatment ) ( p < 0.05 ) , and the DPG refereed daily maintained reduction of 4 cm in the VAS pain ( previous 8.5–4.3 cm ) ( p < 0.02 ) . Concurrent daily consumption of analgesic tablets was reduced in both STG ( p < 0.05 ) and DTG ( p < 0.02 ) . Comparison among groups revealed that analgesia , as well as quality of sleep and disposition , was DTG > STG > PG ( p < 0.05 ) . Participants subjectively found the active device useful . While the application of a single active TENS improved pain relief in fibromyalgia pain , pain and fatigue were further improved when two active devices were simultaneously applied at the low back and cervical area , with no side effects The aim of this study was to investigate the results of a supervised exercise with transcutaneous electrical nerve stimulation ( TENS ) in an exercise controlled study in women with fibromyalgia . Sixty-six women with fibromyalgia who admitted to the outpatient clinic of our hospital were r and omized into two treatment groups . The patients in both groups participated in a supervised combined exercise program for 12 weeks . The women in first group had additional TENS in the first 3 weeks of the study . All subjects were analyzed at the baseline , at the end of the 3rd and 12th weeks . Outcome measures were tender point count ( TPC ) , myalgic pain score ( MPS ) , Fibromyalgia Impact Question naire ( FIQ ) and Short Form-36 ( SF-36 ) Health Survey . Sixty women with fibromyalgia completed the study . The patients in both groups showed improvement in terms of TPC , MPS , FIQ , physical and mental summary scores and total scores of SF-36 at the end of the 3rd and 12th weeks . The improvement in MPS at the third week was higher in the first group ( p = 0.01 ) . But there was no difference in terms of the improvement in MPS between the groups at the end of the 12th week control ( p = 0.87 ) . There was no significant difference between the improvement in the other outcome parameters of the two groups . As a result , supervised exercise program was successful to improve the myalgic pain , functional status and quality of life in women with fibromyalgia . Exercises combined with TENS might be useful due to quick myalgic pain relief in the treatment of fibromyalgia in everyday practice Transcutaneous electrical nerve stimulation ( TENS ) is commonly used for pain relief . However , little robust research exists regarding the combination of parameters required to provide effective doses . This study investigated the hypoalgesic effects of different parameter combinations , applied simultaneously at two sites ( segmental and extrasegmental ) , on pressure pain threshold ( PPT ) in pain‐free humans . Two‐hundred and eight volunteers ( median age 22 years , range 20–26 ) were r and omized to eight groups : six active TENS groups , placebo and control . Parameter combinations were such that frequency always differed at each site ( 110Hz or 4Hz ) , but intensity could be either the same or different levels : high ( to tolerance without pain ) or low ( strong but comfortable ) . TENS was administered to the forearm over the radial nerve and the ipsilateral leg below the fibular head for 30min with monitoring for 30 further minutes . PPT measurements were taken bilaterally from the mid‐point of first dorsal interosseous muscle , by an independent blinded rater , at baseline and at six subsequent 10‐min intervals . Log‐transformed data were analysed using repeated‐ measures analysis of covariance ( baseline values and gender as covariates ) . Those groups using high‐intensity stimulation at the segmental stimulation sites showed significantly greater hypoalgesia than placebo ( p<0.025 in each case ) . The largest hypoalgesic effect was for simultaneous high‐intensity stimulation at segmental and extrasegmental sites , using different frequencies . These results reaffirm that high‐intensity stimulation ( regardless of frequency ) is of fundamental importance in effective dosage BACKGROUND AND PURPOSE It is not fully understood how transcutaneous electrical nerve stimulation ( TENS ) intensity affects mechanical pain threshold . METHOD Sixty-six healthy volunteers ( 13 male , 53 female ; 132 h and s ) without prior experience of TENS participated in the study , which comprised a r and omized single-blind controlled trial . TENS was administered for 20 minutes through electrodes ( 25 x 25 mm ) placed on the h and s and forearms with a fixed frequency of 100 Hz and pulse duration of 150 micros . TENS intensity was r and omized and allocated in a concealed manner so that one arm received TENS with stimulation intensity set at participants ' subjective sensory threshold and the other received TENS with stimulation intensity continuously adjusted by physiotherapists to a strong but comfortable non-painful stimulation . Observers were blinded to stimulation intensity levels . RESULTS Mechanical pain threshold increased significantly , by a mean total of 0.79 kg/cm2 ( 95 % confidence interval [ 95 % CI ] : 0.54 - 1.04 ) ( p < 0.001 ) on the strong but comfortable non-painful stimulation side . The mean change in mechanical pain threshold on the sensory threshold side was 0.19 kg/cm2 and did not reach statistical significance ( 95 % CI-0.15 to 0.51 ) . The mean stimulation intensity level for sensory threshold was 6.7 mA ( 95 % CI : 5.65 to 7.83 ) which was significantly lower ( p < 0.001 ) than the mean stimulation intensity for the strong stimulation , which was 20.5 mA ( 95 % CI 16.6 to 24.4 ) , respectively . The strong stimulation levels were , on average , 3.05 times higher than sensory threshold , but individual variations were large ( range 1.2 - 6.1 ) . CONCLUSIONS TENS administered at a strong but comfortable non-painful stimulation intensity increases mechanical pain threshold ipsi-laterally in healthy subjects , whereas TENS administered at sensory threshold intensity does not . TENS may be ineffective if electrodes are placed contralaterally or distant to the pain site and if stimulation intensity levels are not titrated to subjective strong levels . Further clinical trials are needed to clarify if these findings may also be generalized to population s of chronic pain sufferers & NA ; Previous human studies have shown that the analgesic effect of high‐frequency TENS could not be reversed by low doses of naloxone . The aim of the present study was to reinvestigate the possible contribution of opioid receptors to high‐frequency TENS analgesia by using low ( 0.02 mg/kg ) and high ( 0.14 mg/kg ) doses of naloxone . Naloxone ( high and low doses ) and saline were administered intravenously to young healthy adults using a triple‐blind r and omized cross‐over design . For each visit , TENS ( 100 Hz , 60 & mgr;s ) was applied for 25 min to the external surface of the left ankle . TENS intensity was adjusted to obtain strong but comfortable ( innocuous ) paresthesias . Experimental pain was evoked with a 1 cm2 thermode applied on the lateral aspect of the left heel . Subjective pain scores were obtained before , during and after TENS . Because preliminary analyses showed that the order of presentation affected the pattern of results , only the first visit of every participant could be analyzed without fear of contamination from possible carry‐over effects . These revealed that TENS maintained its analgesic properties following the injection of saline ( p < .001 ) and the injection of a low dose of naloxone ( p < .05 ) . However , when a high dose of naloxone was administered , TENS analgesia was completely blocked ( p = .20 ) . These results suggest that high‐frequency TENS involves opioid receptors . An insufficient amount of opioid antagonist likely prevented previous human studies from discovering the importance of opioid receptors in producing high‐frequency TENS analgesia Objective . Pain is a patient-important outcome , but current reporting in r and omized controlled trials and systematic review s is often suboptimal , impeding clinical interpretation and decision making . Methods . A working group at the 2014 Outcome Measures in Rheumatology ( OMERACT 12 ) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic review s. Results For individual trials , authors should report , in addition to mean change , the proportion of patients achieving 1 or more thresholds of improvement from baseline pain ( e.g. , ≥ 20 % , ≥ 30 % , ≥ 50 % ) , achievement of a desirable pain state ( e.g. , no worse than mild pain ) , and /or a combination of change and state . Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation . When pooling data for meta analysis , authors should consider converting all continuous measures for pain to a 100 mm visual analog scale ( VAS ) for pain and use the established , minimally important difference ( MID ) of 10 mm , and the conventionally used , appreciably important differences of 20 mm , 30 mm , and 50 mm , to facilitate interpretation . Effects ≤ 0.5 units suggest a small or very small effect . To further increase interpretability , the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference . This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups . Conclusion . Presentation of relative effects regarding pain will facilitate interpretation of treatment effects OBJECTIVE To determine the release pattern of serotonin and noradrenaline in the spinal cord in response to transcutaneous electric nerve stimulation ( TENS ) delivered at low or high frequency . DESIGN Prospect i ve r and omized allocation of 3 treatments . SETTING Research laboratory . ANIMALS Male Sprague-Dawley rats ( weight range , 250 - 350 g ) . INTERVENTION Knee joints of rats were inflamed with a mixture of 3 % carrageenan and 3 % kaolin for 24 hours prior to placement of push-pull cannulae into the dorsal horn of the spinal cord . Push-pull sample s were collected in 10-minute intervals before , during , and after treatment with low-frequency TENS ( 4 Hz ) , high-frequency TENS ( 100 Hz ) , or sham TENS . TENS was applied to the inflamed knee joint for 20 minutes at sensory intensity and 100-mus pulse duration . Push-pull sample s were analyzed for serotonin and noradrenaline by high performance liquid chromatography with coulemetric detection . MAIN OUTCOME MEASURES Spinal concentrations of serotonin and noradrenaline . RESULTS Low-frequency TENS significantly increased serotonin concentrations during and immediately after treatment . There was no change in serotonin with high-frequency TENS , nor was there a change in noradrenaline with low- or high-frequency TENS . CONCLUSIONS Low-frequency TENS releases serotonin in the spinal cord to produce antihyperalgesia by activation of serotonin receptors & NA ; This study evaluated the effects of varying frequency , intensity and stimulation site , of transcutaneous electrical nerve stimulation ( TENS ) in an experimental model of pain . In a double‐blind design 240 volunteers were r and omised to one of six experimental TENS groups , a sham TENS or control ( n=30 per group ; gender balanced ) . Two TENS frequencies ( 110 or 4 Hz ) and two intensities ( strong but comfortable or highest tolerable ) at a fixed pulse duration ( 200 & mgr;s ) were applied at three sites relative to the measurement site ( segmentally , extrasegmentally or a combination of these ) , for 30 min . Pressure pain thresholds ( PPT ) were measured using a pressure algometer , in the first dorsal interosseous muscle , every 10 min , during stimulation and for a further 30 min . The high frequency , high intensity segmental , and combined stimulation groups , showed rapid onset and significant hypoalgesic effects . This effect was sustained for 20 min post‐stimulation in the high frequency segmental group . All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group , and none of these groups reached a clinical ly significant hypoalgesic level . Conclusions : The role of TENS frequency , intensity and site are pivotal to achieving optimal hypoalgesic effects , during and after stimulation . Clinical applications of these parameter combinations require further investigations Background : Transcutaneous electrical nerve stimulation ( TENS ) is a modality commonly used in pain management . Objectives : This study investigated the hypoalgesic effects of alternating-frequency TENS ( 4 Hz for 3 s/110 Hz for 3 s ) on pressure pain threshold ( PPT ) . Methods : Two-hundred and eight healthy , pain-free volunteers ( 19 to 59 y old ; 104 males , 104 females ) were r and omized to 8 groups : 6 active TENS groups , placebo , and control ( n=26 per group ) . Parameter combinations were such that alternating-frequency TENS was combined with different levels of intensity “ low ” ( strong but comfortable ) or “ high ” ( strong and uncomfortable but not painful ) . TENS was administered either at the forearm ( segmental stimulation ) , at the ipsilateral leg ( extrasegmental stimulation ) , or at both sites ( dual-site stimulation ) for 30 minutes and monitored for 30 further minutes . PPT measurements were taken bilaterally from the mid-point of first dorsal interosseous muscle , by an independent blinded rater , at baseline and at 6 subsequent 10-minute intervals . Square-root transformed data were analyzed using repeated measures analysis of covariance ( baseline values and sex as covariates ) . Results : Alternating-frequency TENS groups did not achieve significant hypoalgesic effects compared with placebo or control ( P>0.05 ) . The largest increase in PPT ( from baseline ) was 76.6 kPa with low-intensity segmental alternating frequency TENS at the 20-minute stimulation time point . This change from baseline is below a difference of 100 kPa that is considered to be a clinical ly meaningful change in hypoalgesia . Discussion : The alternating-frequency setting does not result in large hypoalgesic effects such as those previously reported using fixed-frequency TENS & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy UNLABELLED This study compared a new transient sham transcutaneous electrical nerve stimulation ( TENS ) that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction . Pressure-pain thresholds ( PPT ) , heat-pain thresholds ( HPT ) , and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after r and omization . Allocation investigators and subjects were asked to identify the treatment administered . The transient sham blinded investigators 100 % of the time and 40 % of subjects compared to the inactive sham that blinded investigators 0 % of the time and 21 % of subjects . Investigators and subjects were blinded only 7 % and 13 % of the time , respectively , with active TENS . Neither placebo treatment result ed in significant changes in PPT , HPT , or pain intensities . Subjects using higher active TENS amplitudes ( > or = 17 mAs ) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes ( < 17 mAs ) . HPTs and pain intensities to tonic heat were not significantly changed . The transient TENS completely blinds investigators to treatment and does not reduce pain , thereby providing a true placebo treatment . PERSPECTIVE This article presents the benefits of a new transient sham TENS device for use in prospect i ve , r and omized , clinical trials . This device facilitates blinding of subjects and investigators to eliminate expectation bias and determine the true efficacy of TENS for use in clinical population Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability . To date , there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation ( TENS ) in the management of pain and improvement in function in individuals with fibromyalgia . Objectives The purpose of this study will be to complete a long-term , multicenter study to assess the effects of TENS in women with fibromyalgia . Design This will be a phase II r and omized , double-blind , placebo-controlled , multicenter clinical trial . Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study . Intervention Participants will be r and omly assigned to 1 of 3 groups : the intervention ( TENS ) , placebo , or no treatment . After completing the r and omized period , all participants will receive the intervention for 1 month . The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity . Measurements The primary outcome will be pain with movement , with secondary outcomes assessing functional abilities , patient-reported outcomes , and quantitative sensory testing . Limitations Because having participants refrain from their typical medications is not practical , their usage and any change in medication use will be recorded . Conclusions The results of this study will provide some of the first evidence from a large-scale , double-blind , placebo-controlled trial on the effectiveness of TENS on pain control and quality -of-life changes in patients with fibromyalgia OBJECTIVE To compare the effects of portable superficial warmth with transcutaneous electrical nerve stimulation on pain in patients with fibromyalgia . METHODS The study had a r and omized cross-over design . A total of 32 patients with fibromyalgia were r and omly assigned to 2 groups . After instruction , the patients treated themselves using a portable device providing superficial warmth ( 42 degrees C ) or a transcutaneous electrical nerve stimulation apparatus . After 3 weeks the patients switched therapy . The patients rated pain intensity on a 0 - 100 numerical rating scale before and after each treatment . After 6 weeks , patients were question ed concerning therapy preference . RESULTS There was no difference in level of pain relief when comparing the 2 treatment modes . Median pain intensity in patients using warmth therapy decreased from 77.5 on the numerical rating scale before treatment to 62.5 after treatment and in patients using transcutaneous electrical nerve stimulation from 80 to 62.5 . Ten patients reported a reduction of 20 units or more on the numerical rating scale after warmth therapy , as did 10 after transcutaneous electrical nerve stimulation . Seventeen of 32 patients preferred warmth therapy and 10 preferred transcutaneous electrical nerve stimulation . CONCLUSION Sensory stimulation with superficial warmth or transcutaneous electrical nerve stimulation yielded comparable temporary pain reduction in patients with fibromyalgia . Both procedures are self-administered , safe and in-expensive Thirty adult fibromyalgia syndrome subjects were r and omly assigned to a massage therapy , a transcutaneous electrical stimulation ( TENS ) , or a transcutaneous electrical stimulation no-current group ( Sham TENS ) for 30-minute treatment sessions two times per week for 5 weeks . The massage therapy subjects reported lower anxiety and depression , and their cortisol levels were lower immediately after the therapy sessions on the first and last days of the study . The TENS group showed similar changes , but only after therapy on the last day of the study . The massage therapy group improved on the dolorimeter measure of pain . They also reported less pain the last week , less stiffness and fatigue , and fewer nights of difficult sleeping . Thus , massage therapy was the most effective therapy with these fibromyalgia patients BACKGROUND Chronic pain , considered to be pain lasting more than three months , is a common and often difficult to treat condition that can significantly impact upon function and quality of life . Treatment typically includes pharmacological and non-pharmacological approaches . Transcutaneous electrical nerve stimulation ( TENS ) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain . OBJECTIVES To provide an overview of evidence from Cochrane Review s of the effectiveness of TENS to reduce pain in adults with chronic pain ( excluding headache or migraine).To provide an overview of evidence from Cochrane Review s of the safety of TENS when used to reduce pain in adults with chronic pain ( excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain ( excluding headache or migraine ) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting . To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain ( excluding headache or migraine ) with a view to recommending strategies to reduce any uncertainty . METHODS Search methods We search ed the Cochrane Data base of Systematic Review s ( CDSR ) , in the Cochrane Library , across all years up to Issue 11 of 12 , 2018 . Selection of review sTwo authors independently screened the results of the electronic search by title and abstract against inclusion /exclusion criteria . We included all Cochrane Review s of r and omised controlled trials ( RCTs ) assessing the effectiveness of TENS in people with chronic pain . We included review s if they investigated the following : TENS versus sham ; TENS versus usual care or no treatment/waiting list control ; TENS plus active intervention versus active intervention alone ; comparisons between different types of TENS ; or TENS delivered using different stimulation parameters . Data extraction and analysis Two authors independently extracted relevant data , assessed review quality using the AMSTAR checklist and applied GRADE judgements where required to individual review s. Our primary outcomes included pain intensity and nature/incidence of adverse effects ; our secondary outcomes included disability , health-related quality of life , analgesic medication use and participant global impression of change . MAIN RESULTS We included nine review s investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain . One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies . We therefore extracted data from eight review s which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies .The included review s followed consistent methods and achieved overall high scores on the AMSTAR checklist . The evidence reported within each review was consistently rated as very low quality . Using review authors ' assessment of risk of bias , there were significant method ological limitations in included studies ; and for all review s , sample sizes were consistently small ( the majority of studies included fewer than 50 participants per group).Six of the eight review s presented a narrative synthesis of included studies . Two review s reported a pooled analysis . Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale ( MD -1.58 , 95 % CI -2.08 to -1.09 , P < 0.001 , I² = 29 % , P = 0.22 , 5 studies , 207 participants ) . However the quality of the evidence was very low due to significant method ological limitations and imprecision . A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention ( SMD -0.85 , 95 % CI -1.36 to -0.34 , P = 0.001 , I² = 83 % , P < 0.001 ) . This pooled analysis was judged as offering very low quality evidence due to significant method ological limitations , large between-trial heterogeneity and imprecision . We considered the approach of combining sham and no intervention data to be problematic since we would predict these different comparisons may be estimating different true effects . All remaining review s also reported pain intensity as an outcome measure ; however the data were presented in narrative review form only . Due to method ological limitation and lack of useable data , we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects , nor for the remaining secondary outcomes : disability , health-related quality of life , analgesic medication use and participant global impression of change for any comparisons . We found the included review s had a number of inconsistencies when evaluating the evidence from TENS studies . Approaches to assessing risk of bias around the participant , personnel and outcome -assessor blinding were perhaps the most obvious area of difference across included review s. We also found wide variability in terms of primary and secondary outcome measures , and inclusion /exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions . AUTHORS ' CONCLUSIONS We found the method ological quality of the review s was good , but quality of the evidence within them was very low . We were therefore unable to conclude with any confidence that , in people with chronic pain , TENS is harmful , or beneficial for pain control , disability , health-related quality of life , use of pain relieving medicines , or global impression of change . We make recommendations with respect to future TENS study design s which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic pain UNLABELLED Evidence from recent animal studies indicates that the analgesic effect of low-frequency transcutaneous electrical nerve stimulation ( TENS ) is reduced in opioid-tolerant animals . The aim of the present study was to compare the analgesic effect of conventional ( high frequency ) and acupuncture-like ( low frequency ) TENS between a group of opioid-treated patients and a group of opioid-naive patients in order to determine if this cross-tolerance effect is also present in humans . Twenty-three chronic pain patients ( 11 who took opioids and 12 who did not ) participated in the study . Participants were assigned in a r and omized crossover design to receive alternately conventional and acupuncture-like TENS . There was a significant reduction in pain during and after conventional TENS when compared to baseline for both the opioid and nonopioid group ( P < .01 ) . For acupuncture-like TENS however , the analgesic effect of TENS was only observed in the nonopioid group ( P < .01 ) , with opioid-treated patients showing no change in pain scores during and after TENS when compared to baseline ( P > .09 ) . The reduced analgesic effect of acupuncture-like TENS in opioid-treated patients is coherent with previous animal studies and suggests that conventional TENS should be preferred in patients taking opioids on a regular basis . PERSPECTIVE This study shows that patients taking opioids on a regular basis are less susceptible to benefit from acupuncture-like TENS . This phenomenon is probably attributable to the fact that the analgesia induced by acupuncture-like TENS and opioids are mediated by the same receptors ( ie , μ opioid receptors ) |
2,365 | 31,735,166 | Results from the included r and omized controlled trials suggested no benefit of treatment for sub clinical hypothyroidism for the large majority of outcomes .
This review found moderate to very low- quality evidence on the benefits and harms of treatment for sub clinical hypothyroidism , with most of the evidence showing no benefit of treatment | This systematic review was conducted to inform the Canadian Task Force on Preventive Health Care recommendations on screening for thyroid dysfunction ( TD ) .
The review sought to answer key questions on the benefits and harms of screening for TD , patients ’ values and preferences for screening , and the benefits and harms of treating screen-detected TD . | PURPOSE The role of thyroxine replacement in sub clinical hypothyroidism remains unclear . We performed a 6-month r and omized , double-blind , placebo-controlled trial to evaluate the effects of thyroxine treatment for mild sub clinical hypothyroidism , defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level ( 0.8 - 16 ng/dL ) . SUBJECTS AND METHODS We r and omly assigned 40 women with mild sub clinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment ( n = 23 ; 50 to 100 microg daily ) or placebo ( n = 17 ) . Health-related quality of life ( Hospital Anxiety and Depression scale , 30-item General Health Question naire ) , fasting lipid profiles , body weight , and resting energy expenditure were measured at baseline and 6 months . RESULTS The most common presenting symptoms were fatigue ( n = 33 [ 83 % ] ) and weight gain ( n = 32 [ 80 % ] ) . At presentation , 20 women ( 50 % ) had elevated anxiety scores and 22 ( 56 % ) had elevated scores on the General Health Question naire . Thirty-five women completed the study . There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic , lipid , or anthropometric variables measured , expressed as the mean change in the thyroxine group minus the mean change in the placebo group : body mass index , -0.3 kg/m(2 ) ( 95 % confidence interval [ CI ] : -0.9 to 0.4 kg/m(2 ) ) ; resting energy expenditure , -0.2 kcal/kg/24 h ( 95 % CI : -1.3 to 1.0 kcal/kg/24 h ) ; and low-density lipoprotein cholesterol , -4 mg/dL ( 95 % CI : -23 to 15 mg/dL ) . There was a significant worsening in anxiety scores in the thyroxine group ( scores increased in 8 of 20 women and were unchanged in 2 of 20 ) compared with the placebo group ( scores increased in 1 of 14 women and were unchanged in 6 of 14 ; P = 0.03 ) . CONCLUSIONS ; We observed no clinical ly relevant benefits from 6 months of thyroxine treatment in women with mild sub clinical hypothyroidism Sub clinical hypothyroidism ( sHT ) affects 5 - 15 % of the general population ; however , the need of lifelong L-T(4 ) therapy is still controversial . As myocardium is a main target of thyroid hormone action , we investigated whether sHT induces cardiovascular alterations . Twenty sHT patients were r and omly assigned to receive placebo or L-T(4 ) therapy and were followed for 1 yr . Twenty sex- and age-matched normal subjects served as controls . Doppler echocardiography and videodensitometric analysis were performed in all subjects . Myocardium textural parameters were obtained as mean gray levels , which were then used to calculate the cyclic variation index ( CVI ; percent systolic/diastolic change in mean gray levels ) . Patients had a significantly higher isovolumic relaxation time ( 3.1 + /- 0.5 vs. 2.6 + /- 0.6 ; P < 0.03 ) , peak A ( 0.77 + /- 0.16 vs. 0.56 + /- 0.13 m/s ; P < 0.01 ) , and preejection/ejection time ( PEP/ET ) ratio ( 0.72 + /- 0.05 vs. 0.57 + /- 0.06 ; P < 0.03 ) and a lower CVI ( P < 0.0001 ) than controls . CVI was inversely related to TSH level ( P < 0.0001 ) and PEP/ET ratio ( P < 0.01 ) . L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio ( P < 0.05 ) , peak A ( P < 0.05 ) , and isovolumic relaxation time ( P < 0.05 ) along with a normalization of CVI . Conversely , no changes were observed in the placebo-treated group . In conclusion , sHT affects both myocardial structure and contractility . These alterations may be reversed by L-T(4 ) therapy Sub clinical hypothyroidism ( sHT ) is associated with dyslipidemia and enhanced cardiovascular risk . We assessed carotid artery intima-media thickness ( IMT , high-resolution ultrasonography ) and lipoprotein profile in 45 sHT patients ( aged 37 + /- 11 yr ) at baseline and after 6 months of r and omized , placebo-controlled L-T(4 ) replacement . In comparison with 32 age- and sex-matched controls , sHT patients had elevated total and low-density lipoprotein ( LDL ) cholesterol and ApoB levels ( P = 0.002 , P = 0.0007 , and P = 0.01 , respectively ) and higher mean-IMT values ( P < 0.0001 ) . In stepwise regression analysis , mean-IMT was positively related ( r(2 ) = 0.71 , P < 0.0001 ) to age , TSH , and LDL cholesterol . L-T(4 ) replacement significantly reduced both total and LDL cholesterol ( P < 0.0001 for both ) and mean-IMT ( by 11 % , P < 0.0001 ) . The decrement in IMT was directly related to the decrements of both total cholesterol and TSH ( P = 0.02 and P = 0.0001 , respectively ) . We conclude that early carotid artery wall alterations are present in sHT patients . Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall can not be clearly decided on the basis of the present results . However , the fact that L-T(4 ) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in sub clinical hypothyroidism OBJECTIVE To evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with sub clinical hypothyroidism ( SCH ) . METHODS In a prospect i ve , double-blind , placebo-controlled study , we enrolled 120 patients --mostly , but not exclusively , premenopausal women -- with SCH . Patients were r and omly assigned to either a levothyroxine-treated group ( n = 60 ) or a placebo ( control ) group ( n = 60 ) . Total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides ( TG ) were measured before and 52 weeks after assignment to either group . RESULTS In the levothyroxine-treated group , the lipoprotein mean values before and after the 52-week study were as follows : TC , 5.05 + /- 0.98 mmol/L versus 4.74 + /- 0.87 mmol/L ( P<.0001 ) ; LDL-C , 3.30 + /- 0.90 mmol/L versus 2.89 + /- 0.59 mmol/L ( P<.01 ) ; TG , 1.18 + /- 0.71 mmol/L versus 0.95 + /- 0.53 mmol/L ( P<.002 ) ; and HDL-C , 1.20 + /- 0.33 mmol/L versus 1.19 + /- 0.32 mmol/L ( P = .29 ) . In the control group , TC , HDL-C , and TG values remained unchanged after 52 weeks in comparison with baseline , but LDL-C mean values increased from 2.79 + /- 0.60 mmol/L to 3.11 + /- 0.77 mmol/L , a change that was statistically significant ( P<.001 ) . At the end of the study , the lipid profile changes between levothyroxine-treated and control groups were compared . Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group ( P<.029 and P<.0001 , respectively ) in comparison with the control group . The difference did not reach statistical significance for TG and HDL-C values . CONCLUSION In premenopausal women , SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated BACKGROUND : Previous studies have suggested an association between sub clinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction . METHODS : Thirty-two female sub clinical hypothyroidism patients were r and omly assigned to 12 months of L-thyroxine replacement or no treatment . Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery , as well as mean carotid artery intima-media thickness , and lipid profiles were studied at baseline and after 12 months of follow-up . RESULTS : The mean ( ±SD ) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09±1.32 and 6.27±1.39 µUI/ml , respectively . No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found . The median L-T4 dose was 44.23±18.13 µg/day . After 12 months , there was a significant decrease in the flow-mediated vasodilatation in the sub clinical hypothyroidism control group ( before : 17.33±7.88 to after : 13.1±4.75 % , p = 0.03 ) , but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group ( before : 16.81±7.0 to after : 18.52±7.44 % , p = 0.39 ) . We did not find any significant change in mean carotid intima-media thickness after 12 months of L-thyroxine treatment . CONCLUSION : Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the sub clinical hypothyroidism state . Large prospect i ve multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in sub clinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients BACKGROUND Mild sub clinical hypothyroidism ( SCH ) affects a large number of people and is known to be a risk factor for dyslipidemia . However , whether mild SCH patients should be treated with L-thyroxine to improve lipid profiles remains controversial . In addition , it is also unclear whether all mild SCH patients can benefit from L-thyroxine treatment , regardless of basal thyrotropin or lipid levels . This study aim ed to assess the effects of L-thyroxine replacement therapy on the lipid profiles of mild SCH patients . METHODS This open-label r and omized controlled trial was performed in Ningyang County , Sh and ong Province , China . A total of 378 mild SCH patients with diagnoses confirmed by two thyroid function tests were r and omly assigned to either the intervention group ( L-thyroxine replacement therapy ) or the control group ( no treatment ) . The primary outcome was a change in serum total cholesterol ( TC ) concentration . RESULTS In all , 369 participants completed the 15-month follow-up period . Reduced TC concentrations were more prominent in the intervention group than they were in the control group ( -0.41 mmol/L vs. -0.17 mmol/L ; p = 0.012 ) , and changes in low-density lipoprotein cholesterol levels exhibited the same trend . Subgroup analyses were performed to assess the effects of L-thyroxine in patients with different thyrotropin or TC levels . When the study population was stratified according to basal thyrotropin concentration , all patients who had received L-thyroxine showed reduced TC levels ( p < 0.001 ) . The treatment was similarly beneficial for all patients , regardless of basal TC level . Even for subjects with TC levels < 5.18 mmol/L , serum TC concentrations remained unchanged in the intervention group ( p = 0.936 ) but increased by 0.35 mmol/L in the control group ( p = 0.004 ) . CONCLUSIONS The findings suggest that mild SCH patients could benefit from L-thyroxine treatment to improve lipid profiles , regardless of basal thyrotropin or TC concentrations Although muscle metabolism and exercise capacity seem to be affected in patients with sub clinical hypothyroidism , there is little evidence indicating improvement of the exercise tolerance due to levothyroxine ( L-T(4 ) ) replacement . The aim of the present study was to verify possible cardiopulmonary changes during exercise in patients with sub clinical hypothyroidism on L-T(4 ) replacement with a normal serum TSH for six months . Twenty-three patients with sub clinical hypothyroidism were r and omized into treated ( no.=11 ) and untreated ( no.=12 ) patients . A cardiopulmonary test was performed with a treadmill , using the modified Balke protocol . Heart rate , oxygen uptake , minute ventilation and other cardiopulmonary parameters were assessed at the 5th minute of exercise . FT4 levels increased while TSH normalized after hormone replacement . Oxygen uptake decreased significantly after hormone replacement ( 24.1+/-6.3 vs 17.1+/-4.2 ml x kg x min(-1 ) ; p=0.03).Minute ventilation also showed an enhanced performance in treated patients ( 28.0+/-8.1 vs 23.5+/-5.6 l x min(-1 ) ; p=0.03 ) , as did the heart rate ( 128+/-17 vs 121+/-17 bpm ; p=0.03 ) . There were no changes in the untreated group . The results demonstrate that submaximal cardiopulmonary exercise performance improved after six months of TSH normalization and this improvement can help enhance the ability to carry out daily life activities in patients with sub clinical hypothyroidism Patients with sub clinical hypothyroidism ( SCH ) have impaired endothelial function probably related to dyslipidemia . The present study compares the effects of simvastatin versus levothyroxine ( LT-4 ) treatment on lipid profile and endothelial function in patients with SCH . Fifty-nine patients with newly diagnosed SCH were enrolled . Patients were r and omized into 3 groups to receive no treatment ( n = 19 ) , LT-4 ( n = 20 ) , or simvastatin ( n = 20 ) . We measured endothelium-dependent vasodilation ( EDV ) and endothelium-independent vasodilation ( EIV ) at baseline and after 8 months . Serum total cholesterol , triglycerides and LDL-cholesterol were significantly lower following simvastatin . EDV increased significantly in simvastatin treatment group ( 7.5 % ± 3.3 % vs 14.0 % ± 4.5 % ( P < 0.01 ) . The improvement of EDV correlated with the percent decrease of LDL-cholesterol ( ρ = 0.68 , P < 0.01 ) . Although LT-4 therapy caused a trend towards an increase in EDV compared to baseline , statistical significance was not achieved . EIV remained unchanged in all three groups . Simvastatin but not LT-4 treatment significantly improves EDV of the brachial artery and dyslipidemia in patients with SCH . Improvement in brachial artery endothelial function may be related in part to a hypolipidemic effect of simvastatin treatment We aim ed to analyze the natural course of sub clinical hypothyroidism , quantify the incidence rate of overt hypothyroidism , and evaluate the risk factors for the development of definitive thyroid failure in elderly patients . One hundred seven patients ( 93 women and 14 men ) over age 55 yr with sub clinical hypothyroidism and no previous history of thyroid disease were prospect ively studied . Subjects were followed up for 6 - 72 months ( mean , 31.7 months ) with repeated determinations of TSH and free T(4 ) . Twenty-eight patients ( 26.8 % ) developed overt hypothyroidism , and 40 ( 37.4 % ) showed normalization of their TSH values . The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population , and 1.76 , 19.67 , and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0 - 9.9 , 10.0 - 14.9 , and 15.0 - 19.9 mU/liter , respectively . Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism , goiter , positive thyroid antibodies ( P < 0.05 ) , and mainly low normal free T(4 ) ( P < 0.01 ) and high TSH ( P < 0.0001 ) concentrations at baseline . A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration ( P < 0.0001 ) . In conclusion , TSH concentration is the most powerful predictor for the outcome of spontaneous sub clinical hypothyroidism in patients over age 55 yr . Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism . We recommend follow-up with clinical and biochemical monitoring in these patients This study investigated whether symptoms and findings of hyperthyroidism exist in patients with sub clinical hyperthyroidism ( SCH ) and sought to determine whether hyperthyroidism treatment improves them . Twenty patients ( mean age : 36.10 + /- 1.41 years ) and 20 healthy controls [ mean age : 36.35 + /- 1.50 years ) were included in the study . The SCH duration of patients was at least 6 months . Bone mineral density ( BMD ) was measured in both patients and controls . The patients were r and omly divided into 2 groups of 10 patients each . Symptoms and findings of hyperthyroidism were evaluated and BMD , 24 hour ambulatory blood pressure , holter measurements and serum lipids were determined initially in both groups and 6 months after the attainment of euthyroidism in the treatment group ( Group 1 ) and after a 6 months follow-up in the observation group ( Group 2 ) . In the patient group , BMD showed a decrease of 1.3 % and 3.9 % in femur neck and L1 - 4 vertebra compared with controls , respectively . But there was no difference in BMD between patients and controls . Fatigue , nervousness , over sweating , tachycardia and tremor improved with treatment . The number of patients with fatigue , nervousness , over sweating and tachycardia increased in Group 2 after the observation . There was no difference between initial values and after a 6 month period from observation or on attainment of euthyroidism in the values of BMD , lipids , minimal and maximal heart rate , total number of ventricular and supraventricular beats and heart rate variability . As a result symptoms of hyperthyroidism were found to be increased in SCH but they partly decreased after antithyroid treatment . But no favourable effects of antithyroid treatment on BMD , heart rate and arrhythmia incidence were found in young , premenopausal patients with SCH during the 6 month period CONTEXT Sub clinical hypothyroidism ( SCH ) and cognitive dysfunction are both common in the elderly and have been linked . It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit . OBJECTIVE Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function . DESIGN AND SETTING We conducted a double-blind placebo-controlled r and omized controlled trial in the context of United Kingdom primary care . PATIENTS Ninety-four subjects aged 65 yr and over ( 57 females , 37 males ) with SCH were recruited from a population of 147 identified by screening . INTERVENTION T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 microg T4 per day for 12 months . Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm . Fifty-two subjects received T4 ( 31 females , 21 males ; mean age 73.5 yr , range 65 - 94 yr ) ; 42 subjects received placebo ( 26 females , 16 males ; mean age 74.2 yr , 66 - 84 yr ) . MAIN OUTCOME MEASURES Mini-Mental State Examination , Middlesex Elderly Assessment of Mental State ( covering orientation , learning , memory , numeracy , perception , attention , and language skills ) , and Trail-Making A and B were administered . RESULTS Eighty-two percent and 84 % in the T4 group achieved euthyroidism at 6- and 12-month intervals , respectively . Cognitive function scores at baseline and 6 and 12 months were as follows : Mini-Mental State Examination T4 group , 28.26 , 28.9 , and 28.28 , and placebo group , 28.17 , 27.82 , and 28.25 [ not significant ( NS ) ] ; Middlesex Elderly Assessment of Mental State T4 group , 11.72 , 11.67 , and 11.78 , and placebo group , 11.21 , 11.47 , and 11.44 ( NS ) ; Trail-Making A T4 group , 45.72 , 47.65 , and 44.52 , and placebo group , 50.29 , 49.00 , and 46.97 ( NS ) ; and Trail-Making B T4 group , 110.57 , 106.61 , and 96.67 , and placebo group , 131.46 , 119.13 , and 108.38 ( NS ) . Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months . CONCLUSIONS This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function CONTEXT Sub clinical hypothyroidism ( SCH ) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range . It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular ( CV ) risk factors and quality of life . OBJECTIVE The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment . DESIGN This was a r and omized , double-blind , crossover study of L-thyroxine and placebo . SETTING The study was conducted with community-dwelling patients . PATIENTS One hundred patients [ mean age ( sd ) 53.8 ( 12 ) yr , 81 females ] with SCH [ mean TSH 6.6 ( 1.3 ) mIU/liter ] without previously treated thyroid or vascular disease . INTERVENTION Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each . MEASUREMENTS Primary parameters were total cholesterol ( TC ) and endothelial function [ brachial artery flow-mediated dilatation ( FMD ) ] , an early marker of atherosclerosis . Patient-reported outcomes were also assessed . RESULTS L-thyroxine treatment reduced TC ( vs. placebo ) from 231.6 to 220 mg/dl , P < 0.001 ; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl , P < 0.05 ; waist to hip ratio from 0.83 to 0.81 , P < 0.006 ; and improved FMD from 4.2 to 5.9 % , P < 0.001 . Multivariate analysis showed that increased serum free T(4 ) level was the most significant variable predicting reduction in TC or improvement in FMD . Furthermore , the symptom of tiredness improved on L-thyroxine therapy , but other patient-reported outcomes were not significantly different after correction for multiple comparisons . CONCLUSION SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness . The CV risk factor reduction is related to the increased level of achieved free T(4 ) concentration OBJECTIVES To evaluate the impact of sub clinical hypothyroidism ( sHT ) treatment on health-related quality of life ( QoL ) , psychiatric symptoms , clinical score , and muscle function . MATERIAL S AND METHODS In this r and omized double-blind study , patients were assigned either to treatment ( n = 35 ) or placebo ( n = 36 ) . Clinical and psychiatric symptoms were assessed by the Zulewski , Hamilton and Beck scales . QoL was assessed by the SF-36 question naire . Assessment s of quadriceps ( QS ) and inspiratory muscle ( IS ) strength were performed by a chair dynamometer and a manuvacuometer . RESULTS Treatment improved IS ( + 11.5 ± 17.2 ; p = 0.041 ) , as did QoL domains " Pain " and " Role Physical " ( + 19.7 ± 15.2 , 0.039 and + 22.1 ± 47.5 , p = 0.054 ; respectively ) . Clinical and psychiatric symptoms showed similar responses to both interventions . CONCLUSIONS sHT treatment improved IS and physical aspects of QoL , despite no impact in other muscle parameters . Clinical score , psychiatric symptoms , and SF-36 domains , based on mental dimensions of QoL may be more susceptible to " placebo effect " in patients with sHT OBJECTIVE We investigated the effects of thyroxine ( T4 ) therapy on the cardiac function in sub clinical hypothyroidism ( SHT ) by using the index of myocardial performance ( IMP ) and the conventional echocardiographic parameters . METHODS Forty-five SHT patients ( F/M:38/7 , age 39.9+/-7.9 ) and 29 healthy subjects ( F/M:25/4 , age 38.3+/-8.6 ) were studied . Patients were r and omly assigned , in a double-blind manner to receive T4 therapy ( group I ) or a placebo ( group II ) and for a period of up to 12 months , were followed up using thyroid function tests and both conventional and Doppler echocardiographic measurements . RESULTS At the baseline , the SHT patients has a significantly higher isovolumic relaxation time ( IRT ) ( 98.3+/-23.7 vs. 81.7+/-14.7<0.01 ) , IMP ( 0.52+/-0.06 vs. 0.42+/-0.05 ; P<0.001 ) , A max ( late mitral peak velocity ) ( 83.4+/-12.6 vs. 74.3+/-13.5 ; P<0.01 ) and significantly lower ( early mitral peak velocity ) Emax/Amax ratio ( 1.19+/-0.18 vs. 1.34+/-0.17 ; P<0.01 ) than the individuals in the control group . In group I , the thyroid hormone profile became normalized after 1 year of L-T4 therapy , but there was no significant change in the left ventricular ( LV ) morphology or systolic function . After 1 year of follow-up , group I showed a significant reduction of MPI ( 0.53+/-0.05 vs. 0.42+/-0.07 ; P<0.001 ) , Amax ( 84.2+/-13.7 vs. 74.5+/-11 ; P<0.001 ) and IRT ( 98.6+/-23.7 vs. 82.9+/- 23.3 ; P<0.001 ) along with a normalization of the E/A ratio ( 1.17+/-0.16 vs. 1.33+/-0.19 ; P<0.001 ) . Conversely , no change was observed in group II . CONCLUSIONS An impairment of left ventricular diastolic function , which may be reversible with T4 therapy , was observed in the SHT patients , and IMP may be useful in the evaluation of LV myocardial dysfunction in these patients The aim of this study was to evaluate the lipid profile of patients with different degrees of hypothyroidism and the effect of levothyroxine replacement in sub clinical hypothyroidism ( SH ) . Initially , a cross-sectional study was performed with 226 participants [ SH = 133 participants , manifest hypothyroidism ( MH ) = 23 participants , and euthyroidism ( EU ) = 70 participants ] . The mean levels of atherogenic lipid variables were greater in MH than in SH and were greater in SH than in EU , although the differences between SH and EU did not reach statistical significance . The SH subgroup with greater serum thyrotropin ( TSH ) levels and that with positive antithyroperoxidase antibodies ( TPO-Ab ) had greater levels of triglycerides and of the atherogenic index Apo B/Apo A. A positive correlation exists between serum TSH and total cholesterol ( rs = 0.167 ; P = 0.006 ) , triglycerides ( rs = 0.219 ; P < 0.001 ) , and ApoB levels ( rs = 0.205 ; P < 0.001 ) . Eleven patients who received levothyroxine ( L-T4 ) treatment and 15 patients who received placebo were reevaluated 1 year after TSH adjusted intervention . A fall in atherogenic variables was observed in the L-T4-treated group , with significance for total cholesterol ( -20.0 vs + 16.1 mg/dL in the placebo group ) and LDL-c ( -21.7 vs + 17.2 mg/dL ) . We concluded that SH leads to an intermediary lipid profile between euthyroid individuals and that found in manifest hypothyroidism and that a significant lipid profile improvement occurred 1 year after L-T4 replacement therapy Although sub clinical hyperthyroidism ( SCH ) has been associated with increased risk of osteoporosis and cardiac arrhythmias , its treatment is still controversial . This study was design ed as a prospect i ve , r and omized , intervention , control- study with a 1-year follow-up in order to investigate whether normalization of serum TSH in SCH using methimazole has favorable bone and heart clinical effects . Fourteen patients with endogenous SCH ( not Graves ’ disease ) were enrolled , 7 ( 5 women/2 men ; group T ) were treated with methimazole ( 2.5–7.5 mg/day ) , and 7 ( 5 women/2 men ; group C ) were followed without treatment ; 10 healthy subjects were also included in the study as controls . Serum free-T3 ( FT3 ) , free-T4 ( FT4 ) and TSH , thyroid echography , bone stiffness index ( SI ) , as measured by heel ultrasonometry , and 24-h electrocardiography monitoring were obtained . SCH patients exhibited higher systolic and diastolic blood pressure than control subjects . They also had a significantly higher number of both ventricular premature beats ( VPB ) ( mean±SEM : 681 ±238 vs 6±2 beats/24 h ; p<0.02 ) and atrial premature beats ( APB ) ( mean±SEM : 495±331 vs 7±2 beats/24 h ; p<0.0001 ) , and a lower SI ( 66±5 vs 96±3 ; p<0.001 ) . Twelve months after normalization of TSH with the use of methimazole , the number of VPB decreased significantly ( 947±443 vs 214±109 beats/24 h ; p<0.05 ) while it remained unchanged in untreated SCH patients ( 414±163 vs 487±152 beats/24 h ; p = ns ) . An insignificant therapy effect was observed as far as APB were concerned ( 826±660 vs 144±75 beats/24 h ; p = ns ) , however their number increased significantly in the untreated group ( 463±49 vs 215±46 beats/ 24 h ; p<0.05 ) . The SI increased significantly as a result of therapy in group T ( 64.1 ±4.8 vs 70.0±5.3 ; p<0.02 ) and was further reduced in group C at the end of the study ( 69.1 ±7.3 vs 62.9±7.1 ; p<0.001 ) . No adverse effect was observed in group T. In conclusion , anti-thyroid therapy seems to have favorable bone and heart clinical effects in subjects with endogenous SCH OBJECTIVES To determine if aging modifies the clinical presentation of hyperthyroidism and the signs of thyrotoxicosis in older people . DESIGN Prospect i ve cohort study . SETTING A French university hospital . SUBJECTS Eighty-four new patients with overt hyperthyroidism confirmed chemically between January 1992 and January 1993 . Controls were 68 older euthyroid patients matched to the older hyperthyroid patients . MEASUREMENTS Comparison of 19 classical signs of hyperthyroidism between 34 older patients ( > or = 70 years ; mean age 80.2 ) and 50 younger patients ( < or = 50 years ; mean age 37.4 ) . Older patients were also compared with controls ( mean age 81.3 ) . RESULTS Three signs were found in more than 50 % of older patients : tachycardia , fatigue , and weight loss . Seven signs were found significantly less frequently in older patients ( P < .001 ) : hyperactive reflexes , increased sweating , heat intolerance , tremor , nervousness , polydipsia , and increased appetite . Only anorexia ( 32 % vs 4 % ) and atrial fibrillation ( 35 % vs 2 % ) were more found frequently in older people ( P < .001 ) . A goiter was present in 94 % of the younger and in 50 % of the older patients ( P < .001 ) . The mean number of clinical signs found in the older subjects was significantly smaller than the number found in younger patients ( 6 vs 10.8 ; P < .001 ) . Comparison with older controls showed three signs that were highly associated with thyrotoxicosis in older people : apathy ( Odd ratio ( OR ) : 14.8 ) , tachycardia ( OR : 11.2 ) , and weight loss ( OR : 8.7 ) . CONCLUSION This study confirms the paucity of clinical signs of hyperthyroidism in older adults . These results suggest the necessity of routine screening for thyroid disease in this age group Many studies have found clinical and metabolic alterations in sub clinical hypothyroidism , however , there are disagreements about the benefits of levothyroxine therapy . The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with sub clinical hypothyroidism . A r and omized double blind , placebo-controlled clinical assay was conducted . Sixty patients were enrolled in stratified r and om allocation by TSH levels that generated similar groups in average : free thyroxine levels , lipid levels , age , clinical score , and sedentary . At 6 months , 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment . The TC and LDL-c variations ( -22.6+/-37.2 and -18.5+/-34.6 mg/dl , respectively ) in the group that received LT4 were statistically different ( p=0.023 and p=0.012 ) from those occurring in the placebo group ( + 7.3+/-37.1 and + 14.7+/-40.6 mg/dl ) . Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab , TSH levels > 8.0 microUI/ml , Body Mass Index > or=25 kg/m2 , and the presence of menopause . We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients . Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary , especially in patients with TSH < 8.0 microUI/ml BACKGROUND Sub clinical hypothyroidism ( SCH ) has been associated with ischemic heart disease ( IHD ) ; however , it is unknown whether treatment of SCH with levothyroxine sodium will reduce the risk of IHD . The aim of this study was to investigate the association between levothyroxine treatment of SCH with IHD morbidity and mortality . METHODS We used the United Kingdom General Practitioner Research Data base to identify individuals with new SCH ( serum thyrotropin levels of 5.01 - 10.0 mIU/L and normal free thyroxine levels ) recorded during 2001 with outcomes analyzed until March 2009 . All analyses were performed separately for younger ( 40 - 70 years ) and older ( > 70 years ) individuals . Hazard ratios ( HRs ) for IHD events ( fatal and nonfatal ) were calculated after adjustment for conventional IHD risk factors , baseline serum thyrotropin levels , and initiation of levothyroxine treatment as a time-dependent covariate . RESULTS Sub clinical hypothyroidism was identified in 3093 younger and 1642 older individuals . For a median follow-up period of 7.6 years , 52.8 % and 49.9 % of younger and older patients with SCH were treated with levothyroxine , respectively . There were 68 incident IHD events in 1634 younger patients treated with levothyroxine ( 4.2 % ) vs 97 IHD events in 1459 untreated individuals ( 6.6 % ) ( multivariate-adjusted HR , 0.61 ; 95 % CI , 0.39 - 0.95 ) . In contrast , in the older group there were 104 events in 819 treated patients ( 12.7 % ) vs 88 events in 823 untreated individuals ( 10.7 % ) ( HR , 0.99 ; 95 % CI , 0.59 - 1.33 ) . CONCLUSIONS Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals , but this was not evident in older people . An appropriately powered r and omized controlled trial of levothyroxine in SCH examining vascular outcomes is now warranted To determine the clinical impact of endogenous sub clinical hyperthyroidism , specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients ( 3 males and 20 females ; mean age , 43 + /- 9 yr ) and 23 age- , sex- , and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey question naires . Because the heart is one of the main target organs of the thyroid hormone , cardiac morphology and function were also investigated by means of st and ard 12-lead electrocardiogram ( ECG ) , 24-h Holter ECG , and complete Doppler echocardiography . Stable endogenous sub clinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study ( TSH , 0.15 + /- 0.1 mU/L ; free T(3 ) , 6.9 + /- 1.1 , pmol/L ; free T(4 ) , 17.2 + /- 2.3 , pmol/L ) . Fifteen patients were affected by multinodular goiter , and eight patients by autonomously functioning thyroid nodule . The mean Symptoms Rating Scale score ( 9 . 8 + /- 5.5 vs. 4.3 + /- 2.2 , P : < 0.001 ) and both the mental ( 36.1 + /- 9.5 vs. 50.0 + /- 8.5 , P : < 0.001 ) and physical ( 42.6 + /- 8.0 vs. 55 . 6 + /- 4.1 , P : < 0.001 ) component scores of Short Form 36 Health Survey documented a significant prevalence of specific symptoms and signs of thyroid hormone excess and notable impairment of quality of life in patients . Holter ECG showed a higher prevalence of atrial premature beats in endogenous sub clinical hyperthyroid patients than in the controls , but the difference was not statistically significant , although the average heart rate was significantly increased in the patients ( P : < 0.001 ) . An increase of left ventricular mass ( 162 + /- 24 vs. 132 + /- 22 g , P : < 0.001 ) due to the increase of septal ( P : = 0.025 ) and posterior wall ( P : = 0.004 ) thickness was observed in patients . Systolic function was enhanced in patients as shown by the significant increase of both fractional shortening ( P : = 0.005 ) and mean velocity of heart rate-adjusted circumferential fiber shortening ( P : = 0.036 ) . The Doppler parameters of diastolic function were significantly impaired in the patients as documented by the reduced early to late ratio of the transmitral flow velocities ( P : < 0.001 ) and the prolonged isovolumic relaxation time ( P : = 0.006 ) . These data indicate that endogenous sub clinical hyperthyroidism has a relevant clinical impact and that it affects cardiac morphology and function . Moreover , they suggest that treatment of persistent endogenous sub clinical hyperthyroidism should be considered also in young and middle-aged patients to attenuate specific symptoms and signs of thyroid hormone excess , ameliorate the quality of life , and avoid the consequences to the heart of long exposure to a mild excess of thyroid hormone OBJECTIVE To assess the potential benefits and risks associated with levothyroxine ( LT4 ) therapy in patients with sub clinical hypothyroidism ( SH ) and concomitant coronary artery disease ( CAD ) . METHODS We enrolled 33 patients ( 4 male and 29 female subjects ) with SH and CAD in this study . The study cohort consisted of 2 groups : 19 patients who were r and omly assigned to receive LT4 therapy , titrated to maintain a normal serum thyrotropin level ( main group ) , and 14 patients who did not receive any LT4 replacement therapy ( control group ) . Variables of the lipid profile and left ventricular diastolic function were measured and 24-hour electrocardiographic monitoring was performed before r and omization and at 6-month follow-up . Medical therapy for the CAD remained unchanged throughout the 6-month study period . RESULTS In the main group , no statistically significant differences were found in the lipids , variables of left ventricular diastolic function , and heart rate pattern between the hypothyroid and euthyroid states . Individual analysis revealed , however , that LT4 therapy was beneficial in terms of lipid abnormalities in those patients with lower body mass index , shorter history of CAD , and higher cholesterol levels at baseline . In the control group , we noted statistically significant prolongation of early filling deceleration time after 6 months , which indicated less flexibility of the left ventricular myocardium and diastolic myocardial dysfunction with long-term SH . In reference to adverse effects of LT4 therapy , 5 of the 19 patients had an increased rate of ventricular premature beats . These 5 patients were significantly older and initially had more supraventricular and ventricular premature beats than the rest of the main group . No ST depressions were recorded during LT4 therapy . CONCLUSION In patients with SH and CAD , LT4 therapy can be beneficial in diminishing lipid abnormalities in those with lower body mass index , briefer duration of CAD , and higher levels of cholesterol at baseline . Patients in our study who experienced adverse effects of LT4 treatment were older and had more supraventricular premature beats at baseline in comparison with the other patients The relationship between sub clinical hypothyroidism ( SCH ) and an atherogenic lipoprotein profile is still controversial . We measured lipoproteins in 49 SCH patients by comparison with 33 euthyroid controls . Total cholesterol ( TC ) , triglyceride , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol ( LDLc ) , apolipoprotein A(1 ) , apolipoprotein B , and lipoprotein ( a ) [ Lp(a ) ] were measured after an overnight fast . Patients were r and omly assigned to levothyroxine therapy or placebo and re-evaluated after 6 months of euthyroidism . SCH patients showed significantly higher TC ( P < 0.01 ) , LDLc ( P = 0.01 ) , and apolipoprotein B ( P = 0.001 ) levels than controls , positively correlated with baseline TSH levels ( P = 0.003 , P = 0.01 , and P = 0.03 , respectively ) . Elevated Lp(a ) levels were significantly more frequent in SCH ( P < 0.05 ) and associated with familial diabetes mellitus and /or coronary heart disease ( P < 0.01 ) . Levothyroxine treatment result ed in a significant decrease of both TC and LDLc concentrations ( P = 0.003 ) , in direct proportion to the respective baseline values ( P < 0.05 and P < 0.01 , respectively ) , whereas no change in Lp(a ) level was observed . No changes occurred in the placebo group . In conclusion , only serum LDLc levels are increased specifically and reversibly in association with SCH . Altered Lp(a ) values reflect a genetic influence rather than a reduced thyroid hormone action OBJECTIVE Sub clinical hypothyroidism affects 5 - 15 % of the general population , is especially prevalent in females , and may be associated with increased morbidity from cardiovascular disease , although it remains controversial . We recently reported a significant increase in the brachial-ankle pulse wave velocity ( baPWV ) , a parameter of arterial stiffening and an independent predictor of cardiovascular events , in sub clinical hypothyroidism without thyroiditis . The current study was performed to assess changes in baPWV in female sub clinical hypothyroidism with autoimmune chronic thyroiditis ( Hashimoto 's disease ) after restoration of normal thyroid function . METHODS In a r and omized placebo-controlled study , 95 female sub clinical hypothyroid patients were monitored for changes in baPWV before and after levothyroxine ( l-T(4 ) ) replacement therapy . Changes in baPWV were also measured in 42 age-matched normal female subjects . RESULTS The baseline baPWV values in patients with sub clinical hypothyroidism were significantly higher than in normal subjects . With attainment of euthyroidism , baPWV showed a significant decrease from 1776.7+/-86.0 to 1674.3+/-79.2 cm/s ( P=0.006 ) in patients treated with l-T(4 ) , but the changes in baPWV and TSH were not correlated . The change in baPWV was significantly and negatively correlated with age and baseline pulse pressure , but multiple regression analysis revealed that these parameters failed to be associated with the change in baPWV . CONCLUSIONS Sustained normalization of thyroid function during l-T(4 ) replacement therapy significantly decreases baPWV in female sub clinical hypothyroid patients with autoimmune chronic thyroiditis , suggesting the improvement of arterial stiffening and , consequently , possible prevention of cardiovascular disease Abstract Objective : To investigate the effect of levothyroxine ( LT4 ) therapy on urinary albumin excretion rate ( UAER ) in early type 2 diabetic nephropathy ( DN ) and sub clinical hypothyroidism ( SCH ) patients with mildly increased thyroid stimulating hormone ( TSH ) levels and serum thyroid peroxidase antibody ( TPO-Ab ) positivity . Methods : Application of r and omized double-blind and placebo-controlled methods . A total of 136 normotensive patients with early type 2 DN and SCH ( TSH 4.0–7.0 mIU/L and TPO-Ab positive ) were selected , and were r and omly divided into two groups for LT4 or placebo treatments , respectively . Changes in UAER , serum creatinine , glomerular filtration rate ( GFR ) , blood pressure , serum uric acid and lipids in patients before and after 48 weeks of treatment were examined and compared between groups . Results : There were no statistically significant differences in the baseline characteristics of study participants between two treatment groups ( p > 0.05 for all ) . After 48 weeks of treatment , compared to the placebo treatment , the LT4 treatment was more effective in reducing total cholesterol ( p < 0.05 ) . Further comparison of therapy-related differences between groups showed that the LT4 treatment was better in reducing UAER , low-density lipoprotein cholesterol and uric acid than the placebo group ( p < 0.01 for all ) . Conclusion : The LT4 treatment may decrease UAER and exert kidney protection effects in early type 2 DN and SCH patients with mildly increased TSH levels and serum TPO-Ab positivity . However , due to the short duration of follow-up and small number of cases , the results of this study need future trials with larger numbers of patients and longer follow-up periods to verify whether such a strategy can provide durable benefits Objective To assess the value of population screening for adult hypothyroidism . Setting Healthy people attending for a general health assessment . Methods A thyroid-stimulating hormone ( TSH ) measurement was performed on people attending for a general health assessment ( women aged 50–79 [ 35–49 with a family history of thyroid disease ] and men aged 65–79 ) . Those with TSH levels above 4.0 mU/L were invited to join a r and omized double-blind crossover trial of thyroxine and placebo , each given in r and om order for four months . On entry a second blood sample was collected for a TSH measurement after the end of the trial to determine whether this would help select individuals for thyroxine treatment . The daily thyroxine dose started at 50 µg and if necessary was increased to achieve a TSH level of 0.6–2.0 mU/L. Results There were 341 ( 8 % ) people with a TSH level above 4.0 mU/L , 110 met eligibility criteria ( 64 agreed to participate ) , and 56 ( 49 women , 7 men ) completed the trial . Among the 15 individuals with a repeat TSH measurement above 4.5 mU/L , 11 reported feeling better on thyroxine than placebo and none reported feeling better on placebo ( P = 0.001 ; four felt no different ) , indicating that in this group 73 % benefitted ( i.e. 11/15 ; 95 % CI 45–92 % ) . The main symptoms relieved were tiredness and loss of memory . There was no indication of harm . In the 41 individuals with a repeat serum TSH of 4.5 mU/L or less : 10 reported feeling better on thyroxine than placebo and 16 better on placebo ( P = 0.42 , 15 felt no different ) . Thus about 8 % of men and women in the specified age groups had a TSH above 4.0 mU/L , and of these about a quarter had a repeat TSH above 4.5 mU/L , of whom about half would benefit from thyroxine treatment . Conclusion The results indicate that screening for hypothyroidism would be worthwhile . Approximately 1 % of people screened would have a better quality of life . Pilot screening programmes for adult hypothyroidism are justified Abstract Despite the increasing evidence for relationships between thyroid dysfunction and neuropsychiatric alterations , the effect of treatment of thyroid disease on various clinical psychiatric outcomes is controversial . The purpose of this study was to investigate the effect of levothyroxine treatment on depressive symptoms in subjects with sub clinical hypothyroidism . A r and omized double-blind placebo-controlled clinical trial was performed . Sixty subjects ( 51 females and 9 males ) with sub clinical hypothyroidism were enrolled . Beck Depression Inventory was completed for all participants at the beginning of the study and 12 weeks after enrollment . The intervention and control groups received levothyroxine and placebo , respectively , for 12 weeks . There were no statistical differences in the total depression score and its subscales between the two groups at the beginning of the study . The Beck Depression Inventory score decreased from 16.79 ± 13.25 to 12.37 ± 10.01 ( p value = 0.04 ) in the intervention group . The change in score was not significant for the control group ( 13.77 ± 11.71 to 11.86 ± 10.71 ; p value= 0.16 ) . The affective subscale of Beck Depression Inventory did not change after 12 weeks of treatment with levothyroxine , while somatic subscale remarkably improved in the intervention group ( p value = 0.02 ) . This study showed the efficacy of treatment of sub clinical hypothyroidism in people with levothyroxine in relation to depressive symptoms |
2,366 | 25,004,920 | Combining fecal DNA markers increased the sensitivity of colorectal cancer and adenoma detection .
Combinations of fecal and serum biomarkers produce higher sensitivities , specificities , and PPVs for early detection of colorectal cancer and adenomas . | There is growing interest in early detection of colorectal cancer as current screening modalities lack compliance and specificity .
This study systematic ally review ed the literature to identify biomarkers for early detection of colorectal cancer and polyps . | Objective Early detection and early treatment are of vital importance to the successful treatment of various cancers . The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test ( FOBT ) for early detection of colorectal cancer ( CRC ) is needed . A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening . Design Exhaled breath and watery stool sample s were obtained from patients with CRC and from healthy controls prior to colonoscopy . Each test group consisted of one sample from a patient with CRC and four control sample s from volunteers without cancer . These five sample s were r and omly and separately placed into five boxes . A Labrador retriever specially trained in scent detection of cancer and a h and ler cooperated in the tests . The dog first smelled a st and ard breath sample from a patient with CRC , then smelled each sample station and sat down in front of the station in which a cancer scent was detected . Results 33 and 37 groups of breath and watery stool sample s , respectively , were tested . Among patients with CRC and controls , the sensitivity of canine scent detection of breath sample s compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99 . The sensitivity of canine scent detection of stool sample s was 0.97 and the specificity was 0.99 . The accuracy of canine scent detection was high even for early cancer . Canine scent detection was not confounded by current smoking , benign colorectal disease or inflammatory disease . Conclusions This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body . These odour material s may become effective tools in CRC screening . In the future , studies design ed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC BACKGROUND Sensitive , specific blood-based tests are difficult to develop unless steps are taken to maximize performance characteristics at every stage of marker discovery and development . We describe a sieving strategy for identifying high-performing marker assays that detect colorectal cancer (CRC)-specific methylated DNA in plasma . METHODS We first used restriction enzyme-based discovery methods to identify marker c and i date s with obviously different methylation patterns in CRC tissue and nonpathologic tissue . We then used a selection process incorporating microarrays and /or real-time PCR analysis of tissue sample s to further test marker c and i date s for maximum methylation in CRC tissue and minimum amplification in tissues from both healthy individuals and patients with other diseases . Real-time assays of 3 selected markers were vali date d with plasma sample s from 133 CRC patients and 179 healthy control individuals in the same age range . RESULTS Restriction enzyme-based testing identified 56 c and i date markers . This group was reduced to 6 with microarray and real-time PCR testing . Three markers , TMEFF2 , NGFR , and SEPT9 , were tested with plasma sample s. TMEFF2 methylation was detected in 65 % [ 95 % confidence interval , 56%-73 % ] of plasma sample s from CRC patients and not detected in 69 % ( 62%-76 % ) of the controls . The corresponding results for NGFR were 51 % ( 42%-60 % ) and 84 % ( 77%-89 % ) ; for SEPT9 , the values were 69 % ( 60%-77 % ) and 86 % ( 80%-91 % ) . CONCLUSIONS The stringent criteria applied at all steps of the selection and validation process enabled successful identification and ranking of blood-based marker c and i date Background About half of Americans 50 to 75 years old do not follow recommended colorectal cancer ( CRC ) screening guidelines , leaving 40 million individuals unscreened . A simple blood test would increase screening compliance , promoting early detection and better patient outcomes . The objective of this study is to demonstrate the performance of an improved sensitivity blood-based Septin 9 ( SEPT9 ) methylated DNA test for colorectal cancer . Study variables include clinical stage , tumor location and histologic grade . Methods Plasma sample s were collected from 50 untreated CRC patients at 3 institutions ; 94 control sample s were collected at 4 US institutions ; sample s were collected from 300 colonoscopy patients at 1 US clinic prior to endoscopy . SEPT9 methylated DNA concentration was tested in analytical specimens , plasma of known CRC cases , healthy control subjects , and plasma collected from colonoscopy patients . Results The improved SEPT9 methylated DNA test was more sensitive than previously described methods ; the test had an overall sensitivity for CRC of 90 % ( 95 % CI , 77.4 % to 96.3 % ) and specificity of 88 % ( 95 % CI , 79.6 % to 93.7 % ) , detecting CRC in patients of all stages . For early stage cancer ( I and II ) the test was 87 % ( 95 % CI , 71.1 % to 95.1 % ) sensitive . The test identified CRC from all regions , including proximal colon ( for example , the cecum ) and had a 12 % false-positive rate . In a small prospect i ve study , the SEPT9 test detected 12 % of adenomas with a false-positive rate of 3 % . Conclusions A sensitive blood-based CRC screening test using the SEPT9 biomarker specifically detects a majority of CRCs of all stages and colorectal locations . The test could be offered to individuals of average risk for CRC who are unwilling or unable to undergo colonscopy OBJECTIVES : The immunological fecal occult blood test ( IFOBT ) has established itself as a more precise marker for colorectal cancer ( CRC ) screening than traditional guaiac-based FOBT . The simpler , cheaper , and more convenient newer office-based IFOBTs have been vali date d for diagnosing CRC . Dimeric isoenzyme of pyruvate kinase , M2-PK , expressed by tumor cells , has as well been proposed as a screening tool for CRC . This is the first study comparing fecal M2-PK as a screening biomarker for CRC against previously evaluated office-based IFOBT and colonoscopy . METHODS : Six hundred forty consecutive subjects ( symptomatic , as well as for CRC screening ) referred for colonoscopy for various indications across five centers in Germany provided the stool sample s for performing M2-PK and an immunochemical FOB strip test . The IFOBT used was a rapid immunochromatographic assay for detection of fecal hemoglobin . For M2-PK , a commercially available s and wich enzyme-linked immunosorbent assay ( ELISA ) was used . The M2-PK test needs 6 h , while the office-based test can be read in just 10 min and is five times cheaper . RESULTS : Office-based IFOBT had sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and positive and negative likelihood ratios ( LR ) of 64.5 , 96.3 , 72.0 , 94.9 , 17.5 , and 0.4 for diagnosing colorectal neoplasia ( CRN ) , while the above performance characteristics for M2-PK at a cutoff value of 4U/mL were 72.4 , 73.8 , 29.0 , 94.8 , 2.8 , and 0.8 respectively . CONCLUSIONS : This office-based IFOBT was found to have significantly higher specificity , PPV , and positive LR as compared with M2-PK . IFOBT proved to be a convenient , noncumbersome , quick , and cheap tool in patients with above-average risk for detection of CRN Purpose Neoplasia cells exfoliated from colorectal epithelium have dysfunctional apoptotic mechanisms , thus it is possible to identify high-molecular weight DNA fragments in feces . This prospect i ve single-center study was performed to evaluate the sensitivity and specificity of fecal-based DNA integrity versus immunological fecal occult blood test ( iFOBT ) and calprotectin for colorectal cancer ( CRC ) and adenoma detection . Methods Feces were collected from 204 subjects and DNA integrity was quantified by quantitative-denaturing high performance liquid chromatography ( QdHPLC ) . Calprotectin and iFOBT were assessed using commercial kits . The diagnostic performance was calculated by receiver operating characteristic ( ROC ) curves analysis . Results A total of 192 fecal specimens were analyzed and 12 sample s were excluded due to DNA degradation . We found long DNA ( L-DNA ) occurrence in feces with a sensitivity of 86 % ( n = 24/28 ) and a specificity of 81 % for CRC detection . To minimize false-positive cases of the developed test , area under the curve of ROC was evaluated such that the specificity was increased to 92 % with decreased sensitivity to 79 % , p = 0.0001 for CRC detection . iFOBT was positive in 51 % ( n = 14/27 ) while calprotectin was positive in 75 % ( n = 18/27 ) . The combination of iFOBT and L-DNA identified a greater number of CRC cases with a sensitivity of 89 % and a specificity of 95 % , p < 0.001 . The combination also improved the sensitivity of polyps , particularly high- grade dysplasia and advanced adenoma ( 33 % , p = 0.0015 ) as opposed to a single evaluation assay ( 17–21 % ) . Conclusions This study illustrates the usefulness of fecal DNA integrity assay by QdHPLC as a non-invasive , easy-to-perform , and reproducible method with a high level of sensitivity in detecting individuals with colorectal neoplasia . Combination of iFOBT and L-DNA improves the sensitivity for CRC and adenoma detection BACKGROUND & AIMS Screening colonoscopy examinations for colorectal cancer are offered in the United States and some European countries . Data on results and adverse effects of screening colonoscopy are limited . In autumn 2002 , colonoscopy was introduced as part of a nationwide cancer screening program in Germany ; it was offered to the general population for individuals 55 years of age or older . We collected and analyzed data from this program . METHODS We performed a prospect i ve cross-sectional study , collecting results from 2,821,392 screening colonoscopies performed at more than 2100 practice s by highly qualified endoscopists in Germany from January 2003 to December 2008 . Data on participation , colorectal adenoma and cancer detection , and complications were collected using st and ardized documentation forms . The data generated were central ly processed and evaluated . RESULTS The cumulative participation rate was 17.2 % of eligible women and 15.5 % of eligible men 55 - 74 years old . The adenoma detection rate ( ADR ) was 19.4 % , with a higher rate in men ( 25.8 % vs 16.7 % in women ) . Advanced adenomas were found in 6.4 % of patients . Carcinomas were detected in 25,893 subjects ( 0.9 % ) ; most were of an early UICC stage ( I , 47.3 % ; II , 22.3 % ; III , 20.7 % ; IV , 9.6 % ) . The ADRs for gastroenterologists and nongastroenterologists were 25.1 % and 22.3 % , respectively ( adjusted odds ratio , 1.18 ; 95 % confidence interval , 1.16 - 1.21 ) . The overall complication rate was 2.8/1000 colonoscopies , and the rate of serious complications was 0.58/1000 colonoscopies . CONCLUSIONS A nationwide colonoscopy screening program that uses highly qualified endoscopists can detect a significant number of adenomas and early-stage carcinomas . The ADR for gastroenterologists was higher than for nongastroenterologists Proliferating cells , particularly the tumor cells , express a dimeric isoenzyme of pyruvate kinase , termed M2‐PK . It 's a direct target of several oncoproteins ; the determination of fecal tumor pyruvate kinase type M2 ( M2‐PK ) might be another promising tool for colorectal cancer ( CRC ) screening . In this study , we have evaluated fecal M2‐PK as a screening biomarker for colorectal neoplasia . It was compared against fecal occult blood ( FOB ) and colonoscopy . Three hundred and seventeen consecutive subjects from 4 different centers were included . Stool specimens were collected before purgation , processed appropriately and were tested for FOB and quantitatively analyzed for M2‐PK . Colonoscopies were performed by experienced endoscopists who were unaware of fecal assay results . At cutoff value of 4 U/ml , fecal M2‐PK assay had a sensitivity , specificity , PPV and NPV of 81.1 , 86.7 , 71.1 and 61.9 % respectively for diagnosing CRC whereas FOBT showed a sensitivity of 36.5 % , specificity of 92.2 % , PPV of 72.9 % and NPV of 71.5 % for CRC . Such low specificity of fecal M2‐PK will lead to unacceptably high number of false positives if it is used for mass CRC screening , leading to unindicated colonoscopies with its associated inconveniences , risks and costs . CRC screening test must have high specificity ; a high sensitivity is not as vital . To conclude , M2‐PK was found to be a poor screening biomarker for CR neoplasia in a subject population at above average risk based on its prospect i ve comparison with colonoscopy . These marginal performance characteristics do not permit its use as a screening tool for CR neoplasia in present clinical setting s. © 2006 Wiley‐Liss , |
2,367 | 22,961,287 | Results In behavioural disorders parent training is a highly promising intervention , which can successfully improve children ’s compliance and bring down rates of conduct problems significantly .
In young children cognitive , emotional and behavioural development can be enhanced through nutritional supplements and by stimulation through play , praise and reading .
Trauma treatments can bring positive results even in severely traumatised children , who remain in unstable living conditions .
In developmental disorders , there are successful prevention strategies as well as programmes that bring children out of isolation and improve their independence .
Some classroom-based interventions for adolescents have reduced symptoms of common mental disorders as well as risk taking behaviours .
Conclusions While many results are still tentative the evidence suggests that it is possible to develop affordable and feasible interventions that significantly improve the lives of affected children , their families and their communities around the world | Purpose Child and adolescent mental health ( CAMH ) problems are common and serious all over the world and are linked to pre-mature deaths and serious dysfunction in adult life .
Effective interventions have been developed in high income countries ( HIC ) , but evidence from low income setting s is scarce and scattered .
The aim of this paper is to identify the most promising interventions in the area of global CAMH . | Background The North-Eastern part of Sri Lanka had already been affected by civil war when the 2004 Tsunami wave hit the region , leading to high rates of posttraumatic stress disorder ( PTSD ) in children . In the acute aftermath of the Tsunami we tested the efficacy of two pragmatic short-term interventions when applied by trained local counselors . Methods A r and omized treatment comparison was implemented in a refugee camp in a severely affected community . 31 children who presented with a preliminary diagnosis of PTSD were r and omly assigned either to six sessions Narrative Exposure Therapy for children ( KIDNET ) or six sessions of meditation-relaxation ( MED-RELAX ) . Outcome measures included severity of PTSD symptoms , level of functioning and physical health . Results In both treatment conditions , PTSD symptoms and impairment in functioning were significantly reduced at one month post-test and remained stable over time . At 6 months follow-up , recovery rates were 81 % for the children in the KIDNET group and 71 % for those in the MED-RELAX group . There was no significant difference between the two therapy groups in any outcome measure . Conclusion As recovery rates in the treatment groups exceeded the expected rates of natural recovery , the study provides preliminary evidence for the effectiveness of NET as well as meditation-relaxation techniques when carried out by trained local counselors for the treatment of PTSD in children in the direct aftermath of mass disasters . Trial registration Clinical Trials.gov Identifier : CONTEXT Despite the importance of mental illness in Africa , few controlled intervention trials related to this problem have been published . OBJECTIVES To test the efficacy of group interpersonal psychotherapy in alleviating depression and dysfunction and to evaluate the feasibility of conducting controlled trials in Africa . DESIGN , SETTING , AND PARTICIPANTS For this cluster r and omized , controlled clinical trial ( February-June 2002 ) , 30 villages in the Masaka and Rakai districts of rural Ug and a were selected using a r and om procedure ; 15 were then r and omly assigned for study ing men and 15 for women . In each village , adult men or women believed by themselves and other villagers to have depressionlike illness were interviewed using a locally adapted Hopkins Symptom Checklist and an instrument assessing function . Based on these interviews , lists were created for each village totaling 341 men and women who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for major depression or subsyndromal depression . Interviewers revisited them in order of decreasing symptom severity until they had 8 to 12 persons per village , totaling 284 . Of these , 248 agreed to be in the trial and 9 refused ; the remainder died or relocated . A total of 108 men and 116 women completed the study and were reinterviewed . INTERVENTION Eight of the 15 male villages and 7 of the 15 female villages were r and omly assigned to the intervention arm and the remainder to the control arm . The intervention villages received group interpersonal psychotherapy for depression as weekly 90-minute sessions for 16 weeks . MAIN OUTCOME MEASURES Depression and dysfunction severity scores on scales adapted and vali date d for local use ; proportion of persons meeting DSM-IV major depression diagnostic criteria . RESULTS Mean reduction in depression severity was 17.47 points for intervention groups and 3.55 points for controls ( P<.001 ) . Mean reduction in dysfunction was 8.08 and 3.76 points , respectively ( P<.001 ) . After intervention , 6.5 % and 54.7 % of the intervention and control groups , respectively , met the criteria for major depression ( P<.001 ) compared with 86 % and 94 % , respectively , prior to intervention ( P = .04 ) . The odds of postintervention depression among controls was 17.31 ( 95 % confidence interval , 7.63 - 39.27 ) compared with the odds among intervention groups . Results from intention-to-treat analyses remained statistically significant . CONCLUSIONS Group interpersonal psychotherapy was highly efficacious in reducing depression and dysfunction . A clinical trial proved feasible in the local setting . Both findings should encourage similar trials in similar setting s in Africa and beyond Background Infection with severe malaria in African children is associated with not only a high mortality but also a high risk of cognitive deficits . There is evidence that interventions done a few years after the illness are effective but nothing is known about those done immediately after the illness . We design ed a study in which children who had suffered from severe malaria three months earlier were enrolled into a cognitive intervention program and assessed for the immediate benefit in cognitive , academic and behavioral outcomes . Methods This parallel group r and omised study was carried out in Kampala City , Ug and a between February 2008 and October 2010 . Sixty-one Ug and an children aged 5 to 12 years with severe malaria were assessed for cognition ( using the Kaufman Assessment Battery for Children , second edition and the Test of Variables of Attention ) , academic skills ( Wide Range Achievement Test , third edition ) and psychopathologic behaviour ( Child Behaviour Checklist ) three months after an episode of severe malaria . Twenty-eight were r and omised to sixteen sessions of computerised cognitive rehabilitation training lasting eight weeks and 33 to a non-treatment group . Post-intervention assessment s were done a month after conclusion of the intervention . Analysis of covariance was used to detect any differences between the two groups after post-intervention assessment , adjusting for age , sex , weight for age z score , quality of the home environment , time between admission and post-intervention testing and pre-intervention score . The primary outcome was improvement in attention scores for the intervention group . This trial is registered with Current Controlled Trials , number IS RCT N53183087 . Results Significant intervention effects were observed in the intervention group for learning mean score ( SE ) , [ 93.89 ( 4.00 ) vs 106.38 ( 4.32 ) , P = 0.04 ] but for working memory the intervention group performed poorly [ 27.42 ( 0.66 ) vs 25.34 ( 0.73 ) , P = 0.04 ] . No effect was observed in the other cognitive outcomes or in any of the academic or behavioural measures . Conclusions In this pilot study , our computerised cognitive training program three months after severe malaria had an immediate effect on cognitive outcomes but did not affect academic skills or behaviour . Larger trials with follow-up after a few years are needed to investigate whether the observed benefits are sustained . Trial registration IS RCT N : IS RCT BACKGROUND The ability of specific behaviour-change interventions to reduce HIV infection in young people remains question able . Since January 1999 , an adolescent sexual and reproductive health ( SRH ) intervention has been implemented in ten r and omly chosen intervention communities in rural Tanzania , within a community r and omised trial ( see below ; NCT00248469 ) . The intervention consisted of teacher-led , peer-assisted in-school education , youth-friendly health services , community activities , and youth condom promotion and distribution . Process evaluation in 1999 - 2002 showed high intervention quality and coverage . A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 ( HSV-2 ) seroprevalence but found substantial improvements in SRH knowledge , reported attitudes , and some reported sexual behaviours . It was postulated that the impact on " upstream " knowledge , attitude , and reported behaviour outcomes seen at the 3-year follow-up would , in the longer term , lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes . A further impact evaluation survey in 2007/8 ( approximately 9 years post-intervention ) tested this hypothesis . METHODS AND FINDINGS This is a cross-sectional survey ( June 2007 through July 2008 ) of 13,814 young people aged 15 - 30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial ( 1999 - 2002 ) . Prevalences of the primary outcomes HIV and HSV-2 were 1.8 % and 25.9 % in males and 4.0 % and 41.4 % in females , respectively . The intervention did not significantly reduce risk of HIV ( males adjusted prevalence ratio [ aPR ] 0.91 , 95%CI 0.50 - 1.65 ; females aPR 1.07 , 95%CI 0.68 - 1.67 ) or HSV-2 ( males aPR 0.94 , 95%CI 0.77 - 1.15 ; females aPR 0.96 , 95%CI 0.87 - 1.06 ) . The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime ( aPR 0.87 , 95%CI 0.78 - 0.97 ) and an increase in reported condom use at last sex with a non-regular partner among females ( aPR 1.34 , 95%CI 1.07 - 1.69 ) . There was a clear and consistent beneficial impact on knowledge , but no significant impact on reported attitudes to sexual risk , reported pregnancies , or other reported sexual behaviours . The study population was likely to have been , on average , at lower risk of HIV and other sexually transmitted infections compared to other rural population s , as only youth who had reached year five of primary school were eligible . CONCLUSIONS SRH knowledge can be improved and retained long-term , but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence . Youth interventions integrated within intensive , community-wide risk reduction programmes may be more successful and should be evaluated . TRIAL REGISTRATION Clinical Trials.gov BACKGROUND In situations of ongoing violence , childhood psychosocial and mental health problems require care . However , re sources and evidence for adequate interventions are scarce for children in low- and middle-income countries . This study evaluated a school-based psychosocial intervention in conflict-affected , rural Nepal . METHODS A cluster r and omized controlled trial was used to evaluate changes on a range of indicators , including psychiatric symptoms ( depression , anxiety , posttraumatic stress disorder ) , psychological difficulties , resilience indicators ( hope , prosocial behavior ) and function impairment . Children ( n = 325 ) ( mean age = 12.7 , SD = 1.04 , range 11 - 14 years ) with elevated psychosocial distress were allocated to a treatment or waitlist group . RESULTS Comparisons of crude change scores showed significant between-group differences on several outcome indicators , with moderate effect sizes ( Cohen d = .41 to .58 ) . After correcting for nested variance within schools , no evidence for treatment effects was found on any outcome variable . Additional analyses showed gender effects for treatment on prosocial behavior ( mean change difference : 2.70 ; 95 % CI , .97 to 4.44 ) , psychological difficulties ( -2.19 ; 95 % CI , -3.82 to -.56 ) , and aggression ( -4.42 ; 95 % CI , -6.16 to -2.67 ) . An age effect for treatment was found for hope ( .90 ; 95 % CI , -1.54 to -.26 ) . CONCLUSIONS A school-based psychosocial intervention demonstrated moderate short-term beneficial effects for improving social-behavioral and resilience indicators among subgroups of children exposed to armed conflict . The intervention reduced psychological difficulties and aggression among boys , increased prosocial behavior among girls , and increased hope for older children . The intervention did not result in reduction of psychiatric symptoms BACKGROUND Depression in women is one of the commonest problems encountered in primary care . We aim ed to compare the effectiveness of a stepped-care programme with usual care in primary -care management of depression in low-income women in Santiago , Chile . METHODS In a r and omised controlled trial , in three primary -care clinics in Chile , 240 adult female primary -care patients with major depression were allocated stepped care or usual care . Stepped care was a 3-month , multicomponent intervention led by a non-medical health worker , which included a psychoeducational group intervention , structured and systematic follow-up , and drug treatment for patients with severe depression . Data were analysed on an intention-to-treat basis . The primary outcome measure was the Hamilton depression rating scale ( HDRS ) administered at baseline and at 3 and 6 months after r and omisation . FINDINGS About 90 % of r and omised patients completed outcome assessment s. There was a substantial between-group difference in all outcome measures in favour of the stepped-care programme . The adjusted difference in mean HDRS score between the groups was -8.89 ( 95 % CI -11.15 to -6.76 ; p<0.0001 ) . At 6-months ' follow-up , 70 % ( 60 - 79 ) of the stepped-care compared with 30 % ( 21 - 40 ) of the usual-care group had recovered ( HDRS score < 8) . INTERPRETATION Despite few re sources and marked deprivation , women with major depression responded well to a structured , stepped-care treatment programme , which is being introduced across Chile . Socially disadvantaged patients might gain the most from systematic improvements in treatment of depression OBJECTIVE To compare the efficacy of an outreach program for young children with cerebral palsy with center-based and " minimal intervention " control groups . DESIGN R and omized controlled trial conducted in a group of 85 children between the ages of 1.5 and 5 years . Urban children were allocated to a daily center-based mother-child group or to monthly training of their parents along with a pictorial guidance manual . Rural children were allocated either to parent training or health advice . Outcome measures were changes in children 's adaptive skills , maternal stress and adaptation to the child , satisfaction with social support , and knowledge of h and ling a physically disabled child . RESULTS Fifty-eight children were successfully followed up . The pattern of change in children 's adaptive skills was as predicted ( ie , least progress in the health advice group ) . Positive effects of intervention also included increased maternal knowledge and perceived helpfulness of support from formal sources . However , maternal adaptation increased most in the health advice group with minimal intervention . When children had attended a program at least 4 times , their skills improved , and mothers ' adaptation did increase . CONCLUSIONS Outreach training for mothers in Bangladesh can help them to improve the skills of their young children with cerebral palsy and is perceived as helpful A school-based intervention for preventing and reducing children 's posttraumatic stress-related symptoms , somatic complaints , functional impairment , and anxiety due to exposure to terrorism was evaluated . In a quasi-r and omized controlled trial , elementary school students were r and omly assigned to an eight-session structured program , " Overshadowing the Threat of Terrorism " or to a waiting list control comparison group . Two months postintervention , the study group reported significant improvement on all measures . The authors conclude that a school-based universal intervention may significantly reduce posttraumatic stress disorder- ( PTSD- ) related symptoms in children repeatedly exposed to terrorist attacks and propose that it serve as a component of a public mental health approach dealing with children exposed to ongoing terrorism in a country ravaged by war and terrorism OBJECTIVE To evaluate the effect of a preventative intervention in Jamaican basic schools on child behaviour and parent-teacher contacts . DESIGN AND METHODS Five basic schools in Kingston , Jamaica , were r and omly assigned to an intervention ( n = 3 ) or control ( n = 2 ) condition . Intervention involved seven whole-day teacher workshops using the Incredible Years Teacher Training Programme supplemented by fourteen lessons on social and emotional skills in each class . Within each classroom ( n = 27 ) , children were screened for behaviour difficulties through teacher report and children with the greatest difficulties were selected for evaluation of outcomes ( 135 children ) . Teachers'reports of child behaviour using the Strengths and Difficulties Question naire and of the quality of teacher-parent contacts were collected at the beginning and end of the school year Multilevel regression analyses controlling for school and classroom were used to evaluate the effects of intervention on child behaviour . RESULTS Significant benefits of intervention were found for children 's conduct problems ( regression coefficient ( b ) = -0.62 , 95 % confidence interval ( CI ) : -0.01 , -1.23 ) , hyperactivity ( b = -0.84 , 95 % CI : -1.57 , -0.11 ) and peer problems ( b = -1.24 , 95 % CI : -1.89 , -0.59 ) . The effect sizes were 0.26 for conduct problems , 0.36 for hyperactivity and 0.71 for peer problems . No significant benefits were found for the prosocial and emotional problems subscales . The intervention also result ed in increases in the number of positive teacher-parent contacts ( p < 0.0001 ) . No benefits were found for the number of negative teacher-parent contacts . CONCLUSION This is a promising approach for reducing children 's externalizing behaviour and peer problems and for improving the quality of teachers ' contacts with parents of children with behaviour problems Background : HIV prevention among young people in southern Africa is a public health priority . There is little rigorous evidence of the effectiveness of different intervention approaches . We describe findings of a cluster r and omized trial of a community-based , multicomponent HIV , and reproductive health intervention aim ed at changing social norms for adolescents in rural Zimbabwe . Methods : Thirty rural communities were r and omized to early or deferred implementation of the intervention in 2003 . Impact was assessed in a representative survey of 18–22-year-olds after 4 years . Participants self-completed a question naire and gave a dried blood spot sample for HIV and herpes simplex virus-2 ( HSV-2 ) antibody testing . Young women had a urinary pregnancy test . Analyses were by intention-to-treat and were adjusted for clustering . Findings : Four thous and six hundred and eighty-four , 18–22-year-olds participated in the survey ( 97.1 % of eligible c and i date s , 55.5 % women ) . Just over 40 % had been exposed to at least 10 intervention sessions . There were modest improvements in knowledge and attitudes among young men and women in intervention communities , but no impact on self-reported sexual behavior . There was no impact of the intervention on prevalence of HIV or HSV-2 or current pregnancy . Women in intervention communities were less likely to report ever having been pregnant . Interpretation : Despite an impact on knowledge , some attitudes , and reported pregnancy , there was no impact of this intervention on HIV or HSV-2 prevalence , further evidence that behavioral interventions alone are unlikely to be sufficient to reverse the HIV epidemic . The challenge remains to find effective HIV prevention approaches for young people in the face of continued and unacceptably high HIV incidence , particularly among young women OBJECTIVE : An estimated 178 million children younger than 5 years in developing countries experience linear growth retardation and are unlikely to attain their developmental potential . We aim ed to evaluate adult benefits from early childhood stimulation and /or nutritional supplementation in growth-retarded children . METHODS : In Kingston , Jamaica , 129 growth-retarded children aged 9 to 24 months took part in a 2-year trial of nutritional supplementation ( 1 kg milk-based formula per week ) and /or psychosocial stimulation ( weekly play sessions to improve mother-child interaction ) . We assessed IQ , educational attainment , and behavior at 22 years old in 105 participants . We used multivariate regressions , weighted to adjust for loss to follow-up , to determine treatment benefits . RESULTS : We found no significant benefits from supplementation . Participants who received stimulation reported less involvement in fights ( odds ratio : 0.36 [ 95 % confidence interval ( CI ) 0.12–1.06 ] ) and in serious violent behavior ( odds ratio : 0.33 [ 95 % CI : 0.11–0.93 ] ) than did participants with no stimulation . They also had higher adult IQ ( coefficient : 6.3 [ 95 % CI : 2.2–10.4 ] ) , higher educational attainment ( achievement , grade level attained , and secondary examinations ) , better general knowledge , and fewer symptoms of depression and social inhibition . CONCLUSIONS : Early psychosocial intervention had wide-ranging benefits in adulthood that are likely to facilitate functioning in everyday life . The reductions in violent behavior are extremely important given the high levels of violence in many developing countries . The study provides critical evidence that early intervention can lead to gains in adult functioning Regular physical activity is associated with a reduced risk of all-cause mortality , and mortality due to cardiovascular disease and cancer . Among adolescents , physical activity is associated with benefits in the prevention and control of emotional distress , and improvement of self-esteem . Countries in transitional epidemiological scenarios , such as Chile , need to develop effective strategies to improve physical activity as a way to face the epidemic of chronic diseases . The objective of this study was to evaluate the effects of a school-based physical activity program on physical fitness and mental health status of adolescents living in a low socioeconomic status area in Santiago , Chile . A quasi-experimental design was used to evaluate the effects of the program over one academic year . The study included 198 students aged 15 years old . Two ninth grade classes were r and omly selected as the intervention group , with two classes of the same grade as controls . A social planning approach was used to develop the intervention . The program was design ed and implemented based on student preferences , teachers ' expertise and local re sources . Changes in physiological and mental health status were assessed . After the intervention , maximum oxygen capacity achieved a significant increase of 8.5 % in the intervention versus 1.8 % in the control group ( p < 0.0001 ) . Speed and jump performance scores improved significantly more in the intervention versus the control group ( p > 0.01 ) . Anxiety score decreased 13.7 % in the intervention group versus 2.8 % in the control group ( p < 0.01 ) , and self-esteem score increased 2.3 % in the intervention group and decreased 0.1 % in the control group after the end of the program ( p < 0.0001 ) . No significant change was observed in the depressive score . Student participation and compliance with the program was > 80 % . To conclude , a school-based program to improve physical activity in adolescents of low socioeconomic status , obtained a high level of participation and achieved significant benefits in terms of physical fitness and mental health status BACKGROUND Depression and anxiety disorders are common mental disorders worldwide . The MANAS trial aim ed to test the effectiveness of an intervention led by lay health counsellors in primary care setting s to improve outcomes of people with these disorders . METHODS In this cluster r and omised trial , primary care facilities in Goa , India , were assigned ( 1:1 ) by computer-generated r and omised sequence to intervention or control ( enhanced usual care ) groups . All adults who screened positive for common mental disorders were eligible . The collaborative stepped-care intervention offered case management and psychosocial interventions , provided by a trained lay health counsellor , supplemented by antidepressant drugs by the primary care physician and supervision by a mental health specialist . The research assessor was masked . The primary outcome was recovery from common mental disorders as defined by the International Statistical Classification of Diseases and Related Health Problems-10th revision ( ICD-10 ) at 6 months . This study is registered with Clinical Trials.gov , number NCT00446407 . FINDINGS 24 study clusters , with an equal proportion of public and private facilities , were r and omised equally between groups . 1160 of 1360 ( 85 % ) patients in the intervention group and 1269 of 1436 ( 88 % ) in the control group completed the outcome assessment . Patients with ICD-10-confirmed common mental disorders in the intervention group were more likely to have recovered at 6 months than were those in the control group ( n=620 [ 65·0 % ] vs 553 [ 52·9 % ] ; risk ratio 1·22 , 95 % CI 1·00 - 1·47 ; risk difference=12·1 % , 95 % CI 1·6%-22·5 % ) . The intervention had strong evidence of an effect in public facility attenders ( 369 [ 65·9 % ] vs 267 [ 42·5 % ] , risk ratio 1·55 , 95 % CI 1·02 - 2·35 ) but no evidence for an effect in private facility attenders ( 251 [ 64·1 % ] vs 286 [ 65·9 % ] , risk ratio 0·95 , 0·74 - 1·22 ) . There were three deaths and four suicide attempts in the collaborative stepped-care group and six deaths and six suicide attempts in the enhanced usual care group . None of the deaths were from suicide . INTERPRETATION A trained lay counsellor-led collaborative care intervention can lead to an improvement in recovery from CMD among patients attending public primary care facilities . FUNDING The Wellcome Trust CONTEXT Prior qualitative work with internally displaced persons in war-affected northern Ug and a showed significant mental health and psychosocial problems . OBJECTIVE To assess effect of locally feasible interventions on depression , anxiety , and conduct problem symptoms among adolescent survivors of war and displacement in northern Ug and a. DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial from May 2005 through December 2005 of 314 adolescents ( aged 14 - 17 years ) in 2 camps for internally displaced persons in northern Ug and a. INTERVENTIONS Locally developed screening tools assessed the effectiveness of interventions in reducing symptoms of depression and anxiety , ameliorating conduct problems , and improving function among those who met study criteria and were r and omly allocated ( 105 , psychotherapy-based intervention [ group interpersonal psychotherapy ] ; 105 , activity-based intervention [ creative play ] ; 104 , wait-control group [ individuals wait listed to receive treatment at study end ] ) . Intervention groups met weekly for 16 weeks . Participants and controls were reassessed at end of study . MAIN OUTCOME MEASURES Primary measure was a decrease in score ( denoting improvement ) on a depression symptom scale . Secondary measures were improvements in scores on anxiety , conduct problem symptoms , and function scales . Depression , anxiety , and conduct problems were assessed using the Acholi Psychosocial Assessment Instrument with a minimum score of 32 as the lower limit for clinical ly significant symptoms ( maximum scale score , 105 ) . RESULTS Difference in change in adjusted mean score for depression symptoms between group interpersonal psychotherapy and control groups was 9.79 points ( 95 % confidence interval [ CI ] , 1.66 - 17.93 ) . Girls receiving group interpersonal psychotherapy showed substantial and significant improvement in depression symptoms compared with controls ( 12.61 points ; 95 % CI , 2.09 - 23.14 ) . Improvement among boys was not statistically significant ( 5.72 points ; 95 % CI , -1.86 to 13.30 ) . Creative play showed no effect on depression severity ( -2.51 points ; 95 % CI , -11.42 to 6.39 ) . There were no statistically different improvements in anxiety in either intervention group . Neither intervention improved conduct problem or function scores . CONCLUSIONS Both interventions were locally feasible . Group interpersonal psychotherapy was effective for depression symptoms among adolescent girls affected by war and displacement . Other interventions should be investigated to assist adolescent boys in this population who have symptoms of depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00280319 OBJECTIVE To determine whether participation in a mind-body skills group program based on psychological self-care , mind-body techniques , and self-expression decreases symptoms of posttraumatic stress disorder ( PTSD ) . METHOD Eighty-two adolescents meeting criteria for PTSD according to the Harvard Trauma Question naire ( which corresponds with 16 of the 17 diagnostic criteria for PTSD in DSM-IV ) were r and omly assigned to a 12-session mind-body group program or a wait-list control group . The program was conducted by high school teachers in consultation with psychiatrists and psychologists and included meditation , guided imagery , and breathing techniques ; self-expression through words , drawings , and movement ; autogenic training and biofeedback ; and genograms . Changes in PTSD symptoms were measured using the Harvard Trauma Question naire . The study was conducted from September 2004 to May 2005 by The Center for Mind-Body Medicine at a high school in the Suhareka region of Kosovo . RESULTS Students in the immediate intervention group had significantly lower PTSD symptom scores following the intervention than those in the wait-list control group ( F = 29.8 , df = 1,76 ; p < .001 ) . Preintervention and postintervention scores ( mean [ SD ] ) for the intervention group were 2.5 ( 0.3 ) and 2.0 ( 0.3 ) , respectively , and for the control group , 2.5 ( 0.3 ) and 2.4 ( 0.4 ) , respectively . The decreased PTSD symptom scores were maintained in the initial intervention group at 3-month follow-up . After the wait-list control group received the intervention , there was a significant decrease ( p < .001 ) in PTSD symptom scores compared to the preintervention scores . CONCLUSIONS Mind-body skills groups can reduce PTSD symptoms in war-traumatized high school students and can be effectively led by trained and supervised schoolteachers Abstract Objective To determine whether dietary supplementation or psychosocial stimulation given to growth retarded ( stunted ) children age 9 - 24 months has long term benefits for their psychosocial functioning in late adolescence . Design Sixteen year follow-up study of a r and omised controlled trial . Setting Poor neighbourhoods in Kingston , Jamaica . Participants Of 129 stunted children identified at age 9 - 24 months , 103 adolescents aged 17 - 18 were followed up . Intervention Supplementation with 1 kg milk based formula each week or psychosocial stimulation ( weekly play sessions with mother and child ) , or both , for two years . Main outcome measures Anxiety , depression , self esteem , and antisocial behaviour assessed by question naires administered by interviewers ; attention deficit , hyperactivity , and oppositional behaviour assessed by interviews with parents . Results Primary analysis indicated that participants who received stimulation had significantly different overall scores from those who did not ( F = 2.047 , P = 0.049 ) . Supplementation had no significant effect ( F = 1.505 , P = 0.17 ) . Participants who received stimulation reported less anxiety ( mean difference - 2.81 , 95 % confidence interval - 5.02 to - 0.61 ) , less depression ( - 0.43 , - 0.78 to - 0.07 ) , and higher self esteem ( 1.55 , 0.08 to 3.02 ) and parents reported fewer attention problems ( - 3.34 , - 6.48 to - 0.19 ) . These differences are equivalent to effect sizes of 0.40 - 0.49 st and ard deviations . Conclusions Stimulation in early childhood has sustained benefits to stunted children 's emotional outcomes and attention Purpose : This study was planned to investigate the effects of individual and group approaches to sensory-perceptual-motor ( SPM ) training on children with cerebral palsy . Method : This study was carried out at the School of Physical Therapy and Rehabilitation of Hacettepe University , Occupational Therapy Unit . Forty-one children who were diagnosed as having spastic diplegic cerebral palsy by the Department of Paediatric Neurology of Hacettepe University were assessed . Forty-one children with cerebral palsy were r and omly divided into three groups . Individual and group SPM training were given to first group ( IND ) ( n 16 ) and second group ( GRP ) ( n 16 ) respectively . The third group was determined as a control group ( n 9 ) and only the home programme was given . All children were evaluated with Ayres Southern California Sensory Integration Test and Physical Ability Test before and after training . The SPM training programmes were applied for 1.5 hours , 3 days per week for 3 months . Results : Estimates of effect sizes were calculated for group , individual and control treatments . Results indicated that both group and individual treatments had a measurable effect that was consistently greater than that of controls . Conclusions : This study shows that programmes of SPM training in individuals and group treatments affect children with cerebral palsy . It was concluded that SPM training in children with cerebral palsy will be applied to combined programmes and the relationship with individual and group treatments developed Objective : This study was conducted ( i ) to study through a r and omized control trial the effect of Kangaroo Mother Care ( KMC ) on breast feeding rates , weight gain and length of hospitalization of very low birth neonates and ( ii ) to assess the acceptability of Kangaroo Mother Care by nurses and mothers . Methods : Babies whose birth weight was less than 1500 Grams were included in the study once they were stable . The effect of Kangaroo Mother Care on breast feeding rates , weight gain and length of hospitalization of very low birth weight neonates was studied through a r and omized control trial in 28 neonates . The Kangaroo group ( n=14 ) was subjected to Kangaroo Mother Care of at least 4 hours per day in not more than 3 sittings . The babies received Kangaroo Care after shifting out from NICU and at home . The control group ( n=14 ) received only st and ard care ( incubator or open care system ) . Attitude of mothers and nurses towards KMC was assessed on Day 3 ± 1 and on day 7 ± 1 after starting Kangaroo Care in a question naire using Likert ’s scale . Results : The results of the clinical trial reveal that the neonates in the KMC group demonstrated better weight gain after the first week of life ( 15.9 ± 4.5 gm/day vs. 10.6 ± 4.5 gm/day in the KMC group and control group respectively p<0.05 ) and earlier hospital discharge ( 27.2 ± 7 vs. 34.6 ± 7 days in KMC and control group respectively , p<0.05 ) . The number of mothers exclusively breastfeeding their babies at 6 week follow-up was double in the KMC group than in the control group ( 12/14 vs. 6/14 ) ( p < 0.05 ) . Conclusion : KMC managed babies had better weight gain , earlier hospital discharge and , more impressively , higher exclusive breast-feeding rates . KMC is an excellent adjunct to the routine preterm care in a nursery BACKGROUND To evaluate the effect on problem behaviors of a universal school-based prevention curriculum of third grade students . METHODS Six regular classes in 1 elementary school were r and omly assigned to an intervention ( n = 208 ) or control ( n = 209 ) group . A 13-session program was offered to students in the intervention group . The Achenbach Child Behavior Checklist ( CBCL ) , parent report , was used to assess problem behaviors at baseline , at the conclusion of the curriculum , and again at 6-month follow up . RESULTS The unadjusted mean estimates of behavioral problems were significantly lower in the intervention group posttest ( at the conclusion of the curriculum ) , -3.53 ( 95 % confidence interval [ CI ] = -6.59 to -0.48 ; p = .023 ) and at the 6-month follow up , -5.22 ( 95 % CI : -8.27 to -2.16 ; p = .001 ) . After adjusting for potential confounders , gender ( female ) , father 's educational status ( high school ) , family relationships ( good and average ) , and child 's age in months , intervention groups ( intervention posttest and intervention after 6-month follow up ) showed significantly lower total behavioral scores . CONCLUSIONS A universal school-based prevention program for Chinese elementary school-age children result ed in a significant positive change in behavioral problems . This is an important finding in the context of the Chinese 1-child policy that places great value on the achievement of the child Background : On December 26 , 2004 , a tsunami hit the southern coast of Sri Lanka , leaving thous and s dead and injured . Previous research has found significant mental health problems among children exposed to major disasters . School-based universal interventions have shown promise in alleviating distress and posttraumatic symptomatology in children and adolescents . This study evaluated the efficacy of a school-based intervention in reducing stress-related symptomatology among Sri Lankan children exposed to the tsunami . Methods : In a quasi-r and omized controlled trial 166 elementary school students ( ages 9–15 ) with significant levels of tsunami exposure and previous traumatic background were r and omly assigned to a 12-session structured program ‘ ERASE Stress Sri Lanka ’ ( ES-SL ) or to a waiting list ( WL ) religious class control group . Students were assessed 1 week prior and 3 months after the intervention on measures of posttraumatic symptomatology [ including posttraumatic stress disorder ( PTSD ) and severity of posttraumatic symptomatology ] , depression , functional problems , somatic problems and hope . Results : This study shows a significant reduction on all outcome variables . PTSD severity , functional problems , somatic complaints , depression and hope scores were all significantly improved in the ES-SL group compared to the WL group . No new cases of PTSD were observed in the experimental group . Conclusion : This study adds to the growing body of evidence suggesting the efficacy of school-based universal approaches in helping children in regions touched by war , terror and disaster and suggests the need to adopt a two-stage approach toward dealing with trauma-exposed students , namely , starting with a universal intervention followed by targeted specialized interventions for those still suffering from posttraumatic distress 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 OBJECTIVE The aim of this study was to assess whether primary health care setting s can be used to engage and provide a preventive intervention to mothers of young children . METHODS Two hundred and twenty-four mothers who had come to the health centers were r and omly assigned to either control group ( CG : n=116 ) or intervention group ( IG : n=108 ) . Mothers in IG were taught about the role of parenting skills in families and common mistakes in parenting in 2-h-weekly sessions for 2 successive weeks . A parenting question naire was distributed to mothers at pre-test and after 8 weeks from the last training session . RESULTS Compared to the CG , there were significant improvements from pre- to post-test in IG on measures of Parenting Scales ( PS ) total scores and Parent-Child Conflict Tactics Scale-modified ( CTSPCm ) total scores . This improvement was maintained at 8-week follow up . CONCLUSION The results support previous international studies that primary health care setting s can be used successfully to engage and provide preventive interventions to mothers of young children . PRACTICE IMPLICATION S Within health centers of Iran where parents routinely bring their children for monitoring of growth or vaccinating against some disease , mothers with a child aged between 2 and 6 years received a parent training . The program gave skills for managing misbehavior and preventing child behavior problems . Mothers reported that their behaviors improved from pre-treatment to post-treatment measured at 8-week follow up . The current work may lead decision-makers to organize this program for all of the health centers to train Iranian mothers It is important to control abnormal behaviour and hyperactivity , and improve cognition in mentally retarded children ( MRC ) , which would help in their education , training and subsequent rehabilitation . Recently it has become known that amongst other side-effects , protracted use of anti-convulsant medication induces cognitive and behavioural dysfunction , which is a major problem in mentally retarded epileptics . In a placebo-controlled study , we confirmed the efficacy of a herbal preparation , BR-16A ( Mentat ) in controlling such behavioural and cognitive deficits in 40 mentally retarded children . The efficacy of this remedy was further evaluated in 19 MRCs with epilepsy . Twelve patients had generalised seizure , 4 with partial and 3 with mixed seizure pattern was continued . Inspite of the usual antiepileptic treatment , the frequency of seizures ranged from 1 to 7 attacks in periods from 1 week to 1 year . With active drug Br-16A , it was possible to note a reduction in seizure frequency . Patients with higher frequency responded better . There was no further increase in the dosage of antiepileptic drugs . There was significant control of other abnormal behaviour as shown by reduction in rating score on the Children 's Behavioural Inventory test . BR-16A was effective in controlling abnormal behaviour , especially hyperactivity and incongruous behaviour in mentally retarded children with and without epilepsy BACKGROUND Re sources to address the needs of parents of intellectually disabled children in developing countries are limited . AIMS The efficacy of interactive group psychoeducation on measures of parental attitude towards intellectual disability was assessed in southern India . METHOD Fifty-seven parents r and omised to 10 weeks of experimental and control therapy were assessed using the Parental Attitude Scale towards the Management of Intellectual Disability . The pre- and post-intervention measurements were done by a single-blinded rater and compared . RESULTS The intervention group had a statistically significant increase in the outcome scores and clinical improvement in the total parental attitude score , orientation towards child-rearing knowledge towards intellectual disability and attitude towards management of intellectual disability , but no change in attitude towards the intellectual disability subscale . CONCLUSIONS Interactive group psychoeducation is effective for changing the attitude of parents with intellectually disabled children , and is a viable option to be developed in situations where re sources are limited OBJECTIVE To assess if eight counseling sessions conducted by women minimally trained as community counselors could reduce the mean level of anxiety and /or depression in women of their own community . DESIGN A r and omized controlled trial . SETTING A lower-middle-class , semi-urban community in Karachi , Pakistan . PARTICIPANTS 366 anxious and /or depressed women providing informed consent . METHOD Through systematic sampling , 1226 women were screened using an indigenous instrument . Out of these , 366 women were found to have anxiety and /or depression and were r and omized to intervention and control groups . Women from the same community were trained in 11 sessions as counselors . Subjects in the intervention group were counseled once weekly for eight weeks by the trained community counselors . After the 8th session , the screening question naire was re-administered to both the groups . RESULTS A significant reduction was found between the mean anxiety and depression scores of the two groups ( p value = 0.000 ) . CONCLUSION Counseling by minimally trained community counselors reduced levels of anxiety and /or depression in women of their own community OBJECTIVES The objective of this study was to access whether there were any therapeutic effects of Thai Traditional Massage ( TTM ) on major behavioral and emotional disturbances in Thai autistic children . DESIGN This was a r and omized controlled trial study . SETTING S/LOCATION The study was conducted at the Rehabilitation Centre of the Thai Red Cross Society . SUBJECTS A total of 60 autistic children between the ages of 3 and 10 completed this study . INTERVENTIONS St and ard sensory integration therapy ( SI ) was compared to the SI with TTM treatments . OUTCOME MEASURES Parents and teachers assessed major behavior disturbances using the Conners ' Rating Scales at 0 and 8 weeks . Sleep Diary ( SD ) , recorded by the parents , assessed the patient 's sleeping patterns every week . RESULTS Sixty ( 60 ) autistic children , mean age 4.67 + /- 1.82 , were recruited . No statistical differences were seen in the demographic and baseline data among both groups . From both the Conners ' Teacher Question naire and SD , statistical improvement was detected for conduct problem , hyperactivity , inattention-passivity , hyperactivity index , and sleeping behavior . However , results from the Conners ' Parent Question naire revealed an improvement only for anxiety ( p = 0.04 ) in the massage group , whereas when both groups were compared , a significant improvement in conduct problem ( p = 0.03 ) and anxiety ( p = 0.01 ) was found . Results indicated that TTM may have a positive effect in improving stereotypical behaviors in autistic children . CONCLUSIONS Over a period of 8 weeks , our findings suggested that TTM could be used as a complementary therapy for autistic children in Thail and BACKGROUND School-based interventions involving teacher and /or child training have been shown to benefit teacher practice s and to prevent conduct problems and improve children 's social and emotional competence in developed countries ; however , we are aware of no reports from a developing country . We conducted a pilot study of the Incredible Years Teacher Training programme and a curriculum unit on social and emotional skills based on concepts and activities drawn from the Incredible Years Dina Dinosaur Classroom Curriculum to determine if this approach is appropriate for use with Jamaican pre-school teachers and children . METHODS Five pre-schools in Kingston , Jamaica were r and omly assigned to an intervention ( 3 pre-schools with 15 classrooms ) or control ( 2 pre-schools with 12 classrooms ) condition . Intervention involved seven whole-day teacher workshops using the Incredible Years Teacher Training programme supplemented by 14 child lessons in each class . The project was evaluated through structured observations of four categories of teacher behaviour and four observer ratings : two rating scales of child behaviour and two rating scales of classroom atmosphere . RESULTS Significant intervention benefits were found to teachers ' behaviour with increased positive behaviour [ b = 7.9 ; 95 % confidence interval ( CI ) : 3.5 , 12.3 ] , reduced negative behaviour ( b = -3.5 ; 95 % CI : -6.6 , -0.2 ) and increases in the extent to which teachers promoted children 's social and emotional skills ( b = 46.4 ; 95 % CI : 11.0 , 81.7 ) . The number of teacher comm and s was not significantly reduced ( b = -2.71 ; 95 % CI : -6.01 , 0.59 ) . Significant intervention benefits were found to ratings of child behaviour with an increase in children 's appropriate behaviour ( b = 5.7 , 95 % CI : 1.0 , 10.8 ) and in children 's interest and enthusiasm ( b = 7.2 , 95 % CI : 0.9 , 13.5 ) . Intervention also benefited classroom atmosphere with increases in opportunities provided for children to share and help each other ( b = 1.3 , 95 % CI : 0.5 , 2.1 ) and in teacher warmth ( b = 1.3 , 95 % CI : 0.9 , 1.8 ) . CONCLUSION This is a promising approach for improving the emotional climate of Jamaican pre-school classrooms and for improving child behaviour and participation Objective : To evaluate the acute efficacy of methylpheni date ( MPH ) in Brazilian male children and adolescents with ADHD . Method : In a 4-day , double-blind , placebo-controlled , r and omized , fix dose escalating , parallel-group trial , 36 ADHD children and adolescents were allocated to two groups : MPH ( n = 19 ) and placebo ( n = 17 ) . Participants were evaluated pre- and posttreatment using the 10-item Conners Abbreviated Rating Scale ( ABRS ) , the Children ’s Global Assessment Scale ( CGAS ) , and a simplified version of the Continuous Performance Test ( CPT ) . Results : The MPH group had a significantly greater decrease in ABRS scores and a significantly higher increase in CGAS scores than the placebo group ( p < 0.01 ) . The MPH group showed also a significantly higher proportion of patients with a robust improvement ( decrement of at least 50 % in the ABRS score after the intervention ) than the placebo group ( p < 0.01 ) . The MPH effect size for the ABRS was 1.05 ( 95 % CI = 0.73 - 1.37 ) . Conclusion : Our results extend the efficacy of MPH on the ADHD core symptoms extensively demonstrated in clinical trials with sample s from some developed countries to a sample from a developing country where a diverse culture may modulate the clinical presentation of the disorder Different rates of suicide have been reported in India . In Vellore , southern India , we have noted that the rates of suicides are several fold higher than those reported anywhere in the world , especially in young women . The department of community health at the Christian Medical College , Vellore , has obtained data prospect ively on births , deaths , and morbidity in a population of 108?000 . We used the verbal autopsy method to assign cause of death . The mortality rates were analysed for 10 years , from 1992 to 2001 , for the age-group 10 - 19 years . Suicides accounted for about a quarter of all deaths in young men and between 50 % and 75 % of all deaths in young women . The average suicide rate for young women was 148 per 100?000 , and for young men 58 per 100?000 . We believe that our findings are reliable . The system of surveillance is well established and the verbal autopsy method has been vali date d. These very high rates of suicide need urgent intervention This study evaluates the initial efficacy of the Parent-Child Interaction Therapy ( PCIT ) for Puerto Rican preschool children aged 4 - 6 years with a diagnosis of attention-deficit/hyperactivity disorder ( ADHD ) , combined or predominantly hyperactive type , and significant behavior problems . Thirty-two families were r and omly assigned to PCIT ( n = 20 ) or a 3.5-month waiting-list condition ( WL ; n = 12 ) . Participants from both groups completed pretreatment and posttreatment assessment s. Outcome measures included child 's ADHD symptoms and behavior problems , parent or family functioning , and parents ' satisfaction with treatment . ANCOVAs with pretreatment measures entered as covariates were significant for all posttreatment outcomes , except mother 's depression , and in the expected direction ( p < .01 ) . Mothers reported a highly significant reduction in pretreatment hyperactivity and inattention and less aggressive and oppositional-defiant behaviors , conduct problems assessed as problematic , parenting stress associated with their child 's behavior , and an increase in the use of adequate parenting practice s. For the WL group , there were no clinical ly significant changes in any measure . Treatment gains obtained after treatment were maintained at a 3.5-month follow-up assessment . PCIT seems to be an efficacious intervention for Puerto Rican families who have young children with significant behavior problems Abstract The aim of this study was to assess the effectiveness of a spiritual-hypnosis assisted therapy ( SHAT ) for treatment of posttraumatic stress disorder ( PTSD ) in children . All children , age 6–12 years ( N=226 ; 52.7 % females ) , who experienced the terrorist bomb blasts in Bali in 2002 , and subsequently were diagnosed with PTSD were studied , through a longitudinal , quasi-experimental ( pre-post test ) , single-blind , r and omized control design . Of them , 48 received group SHAT ( treatment group ) , and 178 did not receive any therapy ( control group ) . Statistically significant results showed that SHAT produced a 77.1 % improvement rate , at a two-year follow up , compared to 24 % in the control group , while at the same time , the mean PTSD symptom score differences were significantly lower in the former group . We conclude that the method of spiritual-hypnosis is highly effective , economic , and easily implemented , and has a potential for therapy of PTSD in other cultures or other catastrophic life-threatening events BACKGROUND Since September 2000 Israeli children have been exposed to a large number of terrorist attacks . A universal , school-based intervention for dealing with the threat of terrorism as well as with terror-related symptoms , ERASE-Stress ( ES ) , was evaluated in a male religious middle school in southern Israel . The program was administered by the homeroom teachers as part of the school curriculum . It consists of 12 classroom sessions each lasting 90 minutes , and included psycho-educational material , skill training and resiliency strategies delivered to the students by homeroom teachers . METHODS One hundred and fourteen 7th and 8th grade students were r and omly assigned to the ES intervention or were part of a waiting list ( WL ) . They were assessed on measures of posttraumatic symptomatology , depression , somatic symptoms and functional problems before and 3 months after the intervention or the WL period . RESULTS Three months after the program ended , students in the experimental group showed significant reduction in all measures compared to the waiting-list control group . CONCLUSIONS The ERASE-Stress program may help students suffering from terror-related posttraumatic symptoms and mitigate the negative effects of future traumatic experiences . Furthermore , a school-based universal program such as the ERASE-Stress may potentially serve as an important and effective component of a community mental health policy for communities affected by terrorism OBJECTIVE To evaluate the comparative effectiveness of a classroom-based psychoeducation and skills intervention ( tier 1 ) and a school-based trauma- and grief-focused group treatment ( tier 2 ) of a three-tiered mental health program for adolescents exposed to severe war-related trauma , traumatic bereavement , and postwar adversity . METHOD A total of 127 war-exposed and predominantly ethnic Muslim secondary school students attending 10 schools in central Bosnia who reported severe symptoms of posttraumatic stress disorder ( PTSD ) , depression , or maladaptive grief and significant impairment in school or relationships were r and omly assigned to one of two experimental conditions . These included either an active-treatment comparison condition ( tier 1 ) , consisting of a classroom-based psychoeducation and skills intervention alone ( n = 61 , 66 % girls , mean age 16.0 years , SD 1.13 ) or a treatment condition composed of both the classroom-based intervention and a 17-session manual-based group therapy intervention ( tier 2 ) , trauma and grief component therapy for adolescents ( n = 66 , 63 % girls , mean age 15.9 years , SD 1.11 ) . Both interventions were implemented throughout the school year . Distressed students who were excluded from the study due to acute risk for harm ( n = 9 ) were referred for community-based mental health services ( tier 3 ) . RESULTS Program effectiveness was measured via reductions in symptoms of PTSD , depression , and maladaptive grief assessed at pretreatment , posttreatment , and 4-month follow-up . Analysis of mean-level treatment effects showed significant pre- to posttreatment and posttreatment to 4-month follow-up reductions in PTSD and depression symptoms in both the treatment and comparison conditions . Significant pre- to posttreatment reductions in maladaptive grief reactions were found only in the treatment condition . Analyzed at the individual case level , the percentages of students in the treatment condition who reported significant ( p < .05 ) pre- to posttreatment reductions in PTSD symptoms ( 58 % at posttreatment , 81 % at 4-month follow-up ) compare favorably to those reported in controlled treatment efficacy trials , whereas the percentages who reported significant reductions in depression symptoms ( 23 % at posttreatment , 61 % at follow-up ) are comparable to , or higher than , those found in community treatment setting s. Lower but substantial percentages of significant symptom reduction were found for PTSD ( 33 % at posttreatment , 48 % at follow-up ) and depression symptoms ( 13 % at posttreatment ; 47 % at follow-up ) in students in the comparison condition . The odds of significant symptom reduction were higher for PTSD symptoms at both posttreatment and 4-month follow-up and for maladaptive grief at posttreatment ( no follow-up was conducted on maladaptive grief ) . Rates of significantly worsened cases were generally rare in both the treatment and comparison conditions . CONCLUSIONS A three-tiered , integrative mental health program composed of schoolwide dissemination of psychoeducation and coping skills ( tier 1 ) , specialized trauma- and grief-focused intervention for severely traumatized and traumatically bereaved youths ( tier 2 ) , and referral of youths at acute risk for community-based mental health services ( tier 3 ) constitutes an effective and efficient method for promoting adolescent recovery in postwar setting Accumulating evidence suggests that AIDS orphanhood status is accompanied by increased levels of psychological distress such as anxiety , depression , intense guilt , shame , and anger . However , few studies have examined the possible reduction of psychological distress in AIDS orphans through the help of interventions that promote well-being . The objective of the study was to evaluate the effects of a school-based peer-group support intervention combined with periodic somatic health assessment s and treatment on the psychosocial well-being of AIDS orphans in the Mbarara District of southwestern Ug and a. In a cluster r and omized controlled design , 326 AIDS orphans aged 10 - 15 years were assigned to either peer-group support intervention combined with monthly somatic healthcare ( n=159 ) or control group ( n=167 ) for follow-up assessment . Baseline and 10 week follow-up psychological assessment s were conducted in both groups using self-administered Beck Youth Inventories . Complete data were available for 298 orphans . After adjusting for baseline scores , follow-up scores for the intervention group in comparison with controls showed significant improvement in depression , anger , and anxiety but not for self-concept . This study demonstrated that peer-group support intervention decreased psychological distress , particularly symptoms of depression , anxiety and anger . Thus , the use of peer-group support interventions should be incorporated into existing school health programs OBJECTIVE Because antiretroviral treatment ( ART ) fails to improve neurocognitive impairment in children with HIV , we completed a pilot study evaluating the feasibility and cognitive benefit of computerized cognitive rehabilitation therapy ( CCRT ) in Ug and an children with HIV . METHOD Sixty Ug and an children with HIV ( 23 on ART ) were r and omly assigned to 10 sessions of Captain 's Log CCRT ( S and ford , 2007 ) training configured for attention and memory skills or no intervention . Kaufman Assessment Battery for Children ( 2nd ed . , KABC-2 ; Kaufman & Kaufman , 2004 ) performance at baseline indicated pervasive neurocognitive impairment . Cognitive ability was assessed before and after training using the Cogstate computerized neuropsychological test ( Darby , Maruff , Collie , & McStephen , 2002 ) . Viral load along with CD4 and CD8 absolute and activation levels also were measured posttest . RESULTS CCRT was well received with a 95 % adherence rate to scheduled training sessions . CCRT intervention children showed greater improvement on a Cogstate card detection task of simple attention ( p = .02 ) , and speed of correct moves on a Groton Maze Learning Task ( p < .001 ) . These analyses were completed using an analysis of covariance model that adjusted Cogstate performance for the child 's age , st and ardized weight for age , gender , socioeconomic status , school grade level , and baseline KABC-2 performance . ART treatment was not related to Cogstate performance or improvement as a result of CCRT . CD4 and CD8 activation levels were correlated with Cogstate improvement specifically for the CCRT group . CONCLUSIONS CCRT was feasible with our study population and improved maze learning and attention on a detection task . This supports previous findings by our group with cerebral malaria survivors ( Bangirana , Giordani , et al. , 2009 ) Abstract The study was conducted in Israel following the 2006 Lebanon war . The purpose was to examine the impact of counseling groups employing an expressive-supportive modality on children and adolescents with war-related or divorce/loss-related trauma symptoms . The 164 children were placed into 18 small groups for 10 weekly sessions . The children were screened for traumatic stress symptoms and then r and omly divided into experimental and control ( wait-list ) conditions . All participants completed the measures of the dependent variables ( trauma symptoms , anxiety ) , a social support measure , and group-process measures ( group relationships , group cohesion , and catharsis ) . Results indicated a significantly sharper reduction in trauma symptoms and anxiety in the experimental group than in the control group , regardless of type of trauma . A reduction in anxiety was predicted by gains in social support and group cohesiveness The aim of this study was to evaluate the short-term impact of a group crisis intervention for children aged 9–15 years from five refugee camps in the Gaza Strip during ongoing war conflict . Children were selected if they reported moderate to severe posttraumatic stress reactions , and were allocated to group intervention ( N=47 ) encouraging expression of experiences and emotions through storytelling , drawing , free play and role-play ; education about symptoms ( N=22 ) ; or no intervention ( N=42 ) . Children completed the CPTSD-RI and the CDI pre- and post-intervention . No significant impact of the group intervention was established on children ’s posttraumatic or depressive symptoms . Possible explanations of the findings are discussed , including the continuing exposure to trauma and the non-active nature of the intervention OBJECTIVE The authors examined moderators and mediators of a school-based psychosocial intervention for children affected by political violence , according to an ecological resilience theoretical framework . METHOD The authors examined data from a cluster r and omized trial , involving children aged 8 - 13 in Central Sulawesi , Indonesia ( treatment condition n = 182 , waitlist control condition n = 221 ) . Mediators ( hope , coping , peer/emotional/play social support ) and moderators ( gender , age , family connectedness , household size , other forms of social support , exposure to political violence , and displacement ) of treatment outcome on posttraumatic stress symptoms and function impairment were examined in parallel process latent growth curve models . RESULTS Compared with the waitlist group , those receiving treatment showed maintained hope , increased positive coping , maintained peer social support , and increased play social support . Of these putative mediators , only play social support was found to mediate treatment effects , such that increases in play social support were associated with smaller reductions in posttraumatic stress disorder ( PTSD ) symptoms . Furthermore , the authors identified a number of moderators : Girls showed larger treatment benefits on PTSD symptoms ; girls , children in smaller households , and children receiving social support from adults outside the household showed larger treatment benefits on function impairment . CONCLUSIONS Findings provide limited evidence for an ecological resilience theoretical framework . On the basis of these findings , the authors recommend a stronger separation between universal prevention ( e.g. , resilience promotion through play ) and selective/indicated prevention ( e.g. , interventions aim ed at decreasing posttraumatic stress symptoms ) . Play-based interventions should be careful to exclude children with psychological distress . In addition , treatment effects may be augmented by selecting girls and socially vulnerable children CONTEXT The psychological rehabilitation of former child soldiers and their successful reintegration into postconflict society present challenges . Despite high rates of impairment , there have been no r and omized controlled trials examining the feasibility and efficacy of mental health interventions for former child soldiers . OBJECTIVE To assess the efficacy of a community-based intervention targeting symptoms of posttraumatic stress disorder ( PTSD ) in formerly abducted individuals . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial recruiting 85 former child soldiers with PTSD from a population -based survey of 1113 Northern Ug and ans aged 12 to 25 years , conducted between November 2007 and October 2009 in camps for internally displaced persons . Participants were r and omized to 1 of 3 groups : narrative exposure therapy ( n = 29 ) , an academic catch-up program with elements of supportive counseling ( n = 28 ) , or a waiting list ( n = 28 ) . Symptoms of PTSD and trauma-related feelings of guilt were measured using the Clinician-Administered PTSD Scale . The respective sections of the Mini International Neuropsychiatric Interview were used to assess depression and suicide risk , and a locally adapted scale was used to measure perceived stigmatization . Symptoms of PTSD , depression , and related impairment were assessed before treatment and at 3 months , 6 months , and 12 months postintervention . INTERVENTION Treatments were carried out in 8 sessions by trained local lay therapists , directly in the communities . MAIN OUTCOME MEASURES Change in PTSD severity , assessed over a 1-year period after treatment . Secondary outcome measures were depression symptoms , severity of suicidal ideation , feelings of guilt , and perceived stigmatization . RESULTS PTSD symptom severity ( range , 0 - 148 ) was significantly more improved in the narrative exposure therapy group than in the academic catch-up ( mean change difference , -14.06 [ 95 % confidence interval , -27.19 to -0.92 ] ) and waiting-list ( mean change difference , -13.04 [ 95 % confidence interval , -26.79 to 0.72 ] ) groups . Contrast analyses of the time × treatment interaction of the mixed-effects model on PTSD symptom change over time revealed a superiority of narrative exposure therapy compared with academic catch-up ( F(1,234.1 ) = 5.21 , P = .02 ) and wait-listing ( F(1,228.3 ) = 5.28 , P = .02 ) . Narrative exposure therapy produced a larger within-treatment effect size ( Cohen d = 1.80 ) than academic catch-up ( d = 0.83 ) and wait-listing ( d = 0.81 ) . CONCLUSION Among former Ug and an child soldiers , short-term trauma-focused treatment compared either with an academic catch-up program including supportive counseling or with wait-listing result ed in greater reduction of PTSD symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00552006 AIM The aim of this study was to determine whether psychosocial stimulation up to the age of 2 years benefits cognition and behaviour at age 6 years in low-birthweight , term-born ( LBW-T ) children ( gestational age > or = 37 wk , birthweight < 2500 g ) , and to compare LBW-T and normal-birthweight ( NBW ) children . METHOD LBW-T Jamaican infants were r and omized at birth to a control group or an intervention group . Children in the intervention group received psychosocial stimulation for 2 years . LBW-T infants were also compared with NBW infants born in the same hospital . IQ , cognitive function , and behaviour were measured at age 6 years in 109 LBW-T infants . The LBW-T group were divided into the intervention group ( 55 out of 70 enrolled , 32 females , 23 males ; mean birthweight 2190 g , SD 200 g ; and the control group ( 54 out of 70 enrolled , 33 females , 21 males ; birthweight 2240 g , SD 180 g ] . These were compared with 73 out of 94 enrolled NBW infants ( 38 females 35 males ; birthweight 3130 g , SD 330 g ) . RESULTS Among the LBW-T children performance IQ scores were higher in the intervention group than in the control group ( regression coefficient [ B ] 4.06 , 95 % confidence interval [ CI ] 0.01 - 7.98 ) as were visual-spatial memory scores ( B 1.12 , 95 % CI 0.45 - 1.87 ) . Children in the intervention group also exhibited fewer behavioural difficulties ( B -2.21 , 95 % CI -4.13 to -0.10 ) than children in the control group . Compared with NBW children , LBW-T children in the control group had poorer selective attention ( B=-3.35 , 95 % CI -5.59 to -1.26 ) and visual-spatial memory ( B=-0.76 , 95 % CI -1.54 to 0.00 ) , but there were no differences in IQ , language , or behaviour . INTERPRETATION Stimulation had sustained benefits in LBW-T infants . Finding few differences between LBW-T and NBW school-aged children concurs with results from other developing countries Objective : Our earlier studies on Ug and an children surviving cerebral malaria showed cognitive deficits mainly in attention and memory . We now present the first study in sub-Saharan Africa to investigate the feasibility and potential benefits of computerized cognitive rehabilitation training on neuropsychological and behavioral functioning of children surviving cerebral malaria . Methods : A r and omized trial in which 65 children admitted 45 months earlier with cerebral malaria were recruited at Mulago Hospital , Kampala , Ug and a. For 8 weeks , 32 of the children received weekly training sessions using Captain 's Log cognitive training software and the other 33 were assigned to a nontreatment condition . Pre- and postintervention assessment s were completed using CogState , a computerized neuropsychological battery , measuring visuomotor processing speed , working memory , learning , attention and psychomotor speed and the Child Behavior Checklist measuring internalizing problems , externalizing problems , and total problems . Results : Preintervention scores were similar between both groups . Treatment effects were observed on visuospatial processing speed [ group effect ( st and ard error ) 0.14 ( 0.03 ) ; p < .001 ] , on a working memory and learning task [ 0.08 ( 0.02 ) ; p < .001 ] , psychomotor speed [ 0.14 ( 0.07 ) ; p = .04 ] , and on internalizing problems [ −3.80 ( 1.56 ) ; p = .02 ] after controlling for age , sex , school grade , quality of the home environment , and weight for age z scores . Similar treatment effects were observed when no adjustments for the above covariates were made . Conclusions : Computerized cognitive training long after the cerebral malaria episode has immediate benefit on some neuropsychological and behavioral functions in African children . The long-term benefit of this intervention needs to be investigated BACKGROUND A r and omised controlled trial comparing group interpersonal psychotherapy with treatment as usual among rural Ug and ans meeting symptom and functional impairment criteria for DSM-IV major depressive disorder or sub-threshold disorder showed evidence of effectiveness immediately following the intervention . AIMS To assess the long-term effectiveness of this therapy over a subsequent 6-month period . METHOD A follow-up study of trial participants was conducted in which the primary outcomes were depression diagnosis , depressive symptoms and functional impairment . RESULTS At 6 months , participants receiving the group interpersonal psychotherapy had mean depression symptom and functional impairment scores respectively 14.0 points ( 95 % CI 12.2 - 15.8 ; P<0.0001 ) and 5.0 points ( 95 % CI 3.6 - 6.4 ; P<0.0001 ) lower than the control group . Similarly , the rate of major depression among those in the treatment arm ( 11.7 % ) was significantly lower than that in the control arm ( 54.9 % ) ( P<0.0001 ) . CONCLUSIONS Participation in a 16-week group interpersonal psychotherapy intervention continued to confer a substantial mental health benefit 6 months after conclusion of the formal intervention BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) is one of the most common childhood psychiatric disorder with a prevalence of 8 - 12 % . Even though psychostimulants remain the treatment of choice , its cost and availability in developing countries limits the usage of the drug . In view of free availability and low cost , a R and omized controlled study was carried out using two second line drugs ( clonidine and carbamazepine ) in a tertiary care hospital , Pondicherry , South India . OBJECTIVE To compare the efficacy of clonidine and carbamazepine in children with ADHD . METHOD With approval of ethics committee , a prospect i ve , Double-blind , R and omized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD ( age group 4 - 12 years ) , over a period of 2 years ( 2005 - 07 ) in a tertiary care hospital , Pondicherry , South India . RESULTS Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine . Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions . CONCLUSION Clonidine can be a safer and cheaper alternative in treatment of children with ADHD , with a predominant effect on their hyperactivity and impulsivity symptoms AIMS The human immunodeficiency virus ( HIV ) potentially causes a significant encephalopathy and result ant developmental delay in infected children . The aim of this study was to determine whether a home-based intervention programme could have an impact on the neurodevelopmental status of children infected with HIV . METHOD A longitudinal , r and omized , controlled trial was conducted . A total of 122 children aged less than 2 years 6 months were assigned to either a comparison or an experimental group . Children in the experimental group were given a home stimulation programme that was up date d every 3 months . The home programme included activities to promote motor , cognitive , and speech and language development . Children in the comparison group received no developmental intervention . Children were assessed by a blinded assessor at baseline , 6 months , and 12 months using the Bayley Scales of Infant Development , 2nd edition . RESULTS The children in this study came from poor socioeconomic background s and their nutritional status was suboptimal . The experimental group included 60 children ( 30 males , 30 females ) with a mean age of 18 months ( SD 8.1 mo ) . The comparison group included 62 children ( 32 males , 30 females ) with a mean age 19 months ( SD 8.2 mo ) . Cognitive and motor development were severely affected at baseline , with 52 % of the children having severe cognitive delay and 72 % having severe motor delay at baseline . Children in the experimental group showed significantly greater improvement in cognitive ( p=0.010 ) and motor ( p=0.020 ) development over time than children in the comparison group . INTERPRETATION A home stimulation programme taught to the caregiver can significantly improve cognitive and motor development in young children infected with HIV Objective : The aim of the present study was to evaluate the therapeutic effectiveness and safety of the clonidine adhesive patch in treating tic disorders . Method : A total of 437 patients , who met Chinese Classification of Mental Disorders – third edition diagnostic criteria for transient tic disorder ( 5 % ) , chronic motor or vocal tic disorder ( 40 % ) or Tourette disorder ( 55 % ) , aged 6–18years , were divided r and omly into an active treatment group and a clinical control group . Participants in the active treatment group were treated with a clonidine adhesive patch and participants in the clinical control group with a placebo adhesive patch for 4weeks . The dosage of the clonidine adhesive patch was 1.0 mg , 1.5 mg or 2.0 mg per week , depending on each participant 's bodyweight . Participants whose Yale Global Tic Severity Scale ( YGTSS ) score decreased < 30 % and Clinical Global Impression score was ≥4 by the end of week 3 were withdrawn from the trial . Results : After 4 weeks of treatment the active treatment group participants ’ YGTSS score was significantly lower than that of the clinical control group ( F=4.63 , p=0.03 ) . Further , the active treatment group had a significantly better therapeutic response than the clinical control group ( χ2=9.15 , p=0.003 ) . The response rate in the active treatment group was 68.85 % compared to 46.85 % in the clinical control group ( χ2=16.98 , p=0.0001 ) . The rate of adverse events was low ( active treatment group , 3.08 % ; clinical control group , 7.21 % ) and did not differ between the two groups . Conclusions : The clonidine adhesive patch is effective and safe for tic disorders |
2,368 | 29,405,037 | Stratified analysis shows no effect modification with steroids ; we present aggregate effect estimates .
Authors ' conclusions Glycerol was the only osmotic therapy evaluated , and data from trials to date have not demonstrated an effect on death .
Glycerol may reduce neurological deficiency and deafness | Abstract Background Every day children and adults die from acute community‐acquired bacterial meningitis , particularly in low‐income countries , and survivors risk deafness , epilepsy and neurological disabilities .
Osmotic therapies may attract extra‐vascular fluid and reduce cerebral oedema , and thus reduce death and improve neurological outcomes .
This is an up date of a Cochrane Review first published in 2013 .
Objectives To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality , deafness and neurological disability . | Background and Purpose — The aim of this study was to evaluate the effects of hypertonic saline in stroke patients with increased intracranial pressure ( ICP ) after conventional therapy with mannitol had failed . Methods — Twenty-two episodes of ICP crisis occurred in 8 patients in whom the st and ard treatment of 200 mL of 20 % mannitol was not effective . ICP crisis was defined as an increase in ICP of 20 mm Hg ( n=18 ) , pupillary abnormality ( n=3 ) , or a combination of both ( n=1 ) . The patients were treated with 75 mL of 10 % saline over the course of 15 minutes . ICP , mean arterial blood pressure , and cerebral perfusion pressure were monitored for 4 hours . Blood gases , hematocrit , hemoglobin , pH , osmolarity , and electrolytes levels were measured before and 15 and 60 minutes after the start of infusion . Treatment was regarded as effective if ICP decreased > 10 % or the pupillary reaction had normalized . Results — Treatment was effective in all 22 episodes . The maximum ICP decrease was 9.9 mm Hg 35 minutes after the start of infusion . Thereafter , ICP began to rise again . There was no constant effect on mean arterial blood pressure , whereas cerebral perfusion pressure was consistently increased . Blood osmolarity rose by 9 mmol/L and serum sodium by 5.6 mmol/L. Potassium levels , hemoglobin , hematocrit , and pH were slightly decreased . No unexpected side effects were noted . Conclusions — Infusion of 75 mL hypertonic ( 10 % ) saline decreases elevated ICP and increases cerebral perfusion pressure in stroke patients in whom mannitol had failed . The effect on the ICP and cerebral perfusion pressure reaches its maximum after the end of infusion and is seen for 4 hours Abstract A double-blind evaluation of the effects of glycerol administration intravenously for 4 or 6 days in patients with acute stroke was completed in a stroke centre . Fifty-four patients with acute cerebral infa rct ion and eight patients with spontaneous intracerebral haemorrhage were admitted to the study . The neurological status was evaluated by use of a neurological scoring system . Patients with cerebral infa rct ion treated with glycerol showed significant improvement in neurological status compared to the patients treated with placebo ( BACKGROUND In sub-Saharan Africa , bacterial meningitis is common and is associated with a high mortality . Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world , but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus ( HIV ) infection . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of dexamethasone ( 16 mg twice daily for 4 days ) and an open-label trial of intramuscular versus intravenous ceftriaxone ( 2 g twice daily for 10 days ) in adults with an admission diagnosis of bacterial meningitis in Blantyre , Malawi . The primary outcome was death at 40 days after r and omization . RESULTS A total of 465 patients , 90 % of whom were HIV-positive , were r and omly assigned to receive dexamethasone ( 233 patients ) or placebo ( 232 patients ) plus intramuscular ceftriaxone ( 230 patients ) or intravenous ceftriaxone ( 235 patients ) . There was no significant difference in mortality at 40 days in the corticosteroid group ( 129 of 231 patients ) as compared with the placebo group ( 120 of 228 patients ) by intention-to-treat analysis ( odds ratio , 1.14 ; 95 % confidence interval [ CI ] , 0.79 to 1.64 ) or when the analysis was restricted to patients with proven pneumococcal meningitis ( 68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo ) ( odds ratio , 1.10 ; 95 % CI , 0.68 to 1.77 ) . There were no significant differences between groups in the outcomes of disability and death combined , hearing impairment , and adverse events . There was no difference in mortality with intravenous ceftriaxone ( 121 of 230 patients ) as compared with intramuscular ceftriaxone ( 128 of 229 patients ) ( odds ratio , 0.88 ; 95 % CI , 0.61 to 1.27 ) . CONCLUSIONS Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity . In this setting , intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis . ( Current Controlled Trials number , IS RCT N31371499 [ controlled-trials.com ] . ) Background Several reports have suggested that raised intracranial pressure ( ICP ) is a major contributor to death among children with cerebral malaria . Mannitol , an osmotic diuretic , effectively lowers ICP and is used to treat post-traumatic raised ICP . It is not clear whether intravenous mannitol given to children with cerebral malaria improves clinical outcome . The objective of this study was to determine the effect of mannitol as adjunct therapy on the clinical outcome of children with cerebral malaria . Methods This r and omized double-blind placebo controlled clinical trial was carried out at the Emergency Paediatric ward of Mulago Hospital , Ug and a 's national referral and teaching hospital . One hundred and fifty six children aged 6 to 60 months with cerebral malaria were r and omized to either one dose of mannitol 1 g/kg or placebo , in addition to intravenous quinine . Main outcome measures included coma recovery time ; time to sit unsupported , begin oral intake ; duration of hospitalization ; death and adverse effects . Results Time to regain consciousness ( p = 0.11 ) , sit unsupported ( p = 0.81 ) , time to start oral intake ( p = 0.13 ) and total coma duration ( p = 0.07 ) were similar in both groups . There was no significant difference in the mortality between the placebo ( 13/80 or 16.3 % ) and mannitol ( 10/76 or 13.2 % ) groups : RR = 1.2 ( CI 0.5–2.7 ) . No adverse effects were observed after administration of mannitol . Conclusion Mannitol had no significant impact on clinical outcome of cerebral malaria . It is difficult to recommend intravenous mannitol as adjunct therapy for childhood cerebral malaria . Clinical registration number Clinical Trials.gov ID : Background : The burden that spontaneous bacterial meningitis ( SBM ) currently represents among HIV-1-infected patients is poorly known . Methods : We prospect ively evaluated 32 episodes of SBM in HIV-1-infected patients from the VACH ( VIH-Aplicación de Control Hospitalario ) Cohort and compared findings with those of 267 episodes in uninfected persons , matched by age and year of infection . A group of 13,187 HIV-1-infected patients from the VACH Cohort were used to identify predictors for acquiring SBM . Results : Between 1997 and 2006 , we found 32 episodes of SBM among HIV-1-infected patients for an annual incidence rate of 62.0 cases per 100,000 population compared with 3.2 ( 3.0 to 3.4 ) per 100,000 population for uninfected patients ( P < 0.001 ) . The last CD4 ≥200/mm3 count was the only predictor for developing SBM . Compared with uninfected , HIV-1-infected patients with SBM had a greater prevalence of primary extrameningeal infection , especially pneumonia ( P = 0.02 ) , bacteremia ( P = 0.02 ) , focal neurologic signs ( P = 0.005 ) , seizures ( P = 0.06 ) , a lower cerebrospinal fluid to blood glucose ratio ( P = 0.02 ) , and a lower prevalence of nuchal rigidity ( P = 0.005 ) . Streptococcus pneumoniae was the most frequent etiologic agent among HIV-1-infected patients . HIV-1-infected patients had neurologic complications more frequently ( P = 0.02 ) , a higher overall case fatality rate ( P = 0.004 ) , and greater incidence of neurologic sequelae ( P = 0.001 ) . Conclusions : Even in the highly active antiretroviral therapy era , the risk of developing SBM is 19 times higher among HIV-1-infected patients than among uninfected ones . It tends to present in severely immunosuppressed patients not previously vaccinated and off antiretroviral therapy , with a concomitant extrameningeal infection , bacteremia , and focal neurologic signs , and is caused by S. pneumoniae . SBM in HIV-1-infected patients carries a worse prognosis than in uninfected ones both in terms of lethality and sequelae Background and Purpose This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infa rct ion in whom intracerebral hemorrhage was rigorously excluded . Methods Within 48 hours of symptoms from their first ischemic stroke , 113 hospital in patients were r and omized into the trial , provided that hemorrhage was excluded by computed tomography and informed consent was obtained . Patients were stratified into alert , semicoma , and coma groups using the Glasgow Coma Scale . Treatment was allocated according to a double-blind , r and omized protocol ; 56 patients received 500 mL of 10 % glycerol in saline over 4 hours on 6 consecutive days , and 57 patients received corresponding placebo treatment with saline . Using a variety of objective scoring systems , patient follow-up was up to 6 months . Results Corresponding measures of outcome in the glycerol and placebo groups were similar . At 6 months , respective mortality rates were 17 of 56 and 16 of 57 , and mean ±SD improvements in scores were 9.98±14.40 vs 10.51±12.68 ( long-term ) , 1.12±7.20 vs 1.57±6.30 ( prognostic ) , −1.94±5.53 vs −2.06±5.34 ( Glasgow Coma Scale ) , and 21.72±23.40 vs 11.94± 18.10 ( Barthel Index rating in survivors ) . Hemolysis ( generally sub clinical ) was the only adverse effect . Conclusions There was no clinical ly or statistically significant difference in outcome between the groups ; a trend toward greater functional recovery among survivors was evident after treatment with glycerol Objectives Traumatic brain injury ( TBI ) is still a major cause of mortality and morbidity . Recent trials have failed to demonstrate a beneficial outcome from therapeutic treatments such as corticosteroids , hypothermia and hypertonic saline . We investigated the effect of a new hyperosmolar solution based on sodium lactate in controlling raised intracranial pressure ( ICP ) . Design and setting Prospect i ve open r and omized study in an adult ICU . Patients Thirty-four patients with isolated severe TBI ( Glasgow Coma Scale ≤ 8) and intracranial hypertension were allocated to receive equally hyperosmolar and isovolumic therapy , consisting of either mannitol or sodium lactate . Rescue therapy by crossover to the alternative treatment was indicated when ICP could not be controlled . The primary endpoint was efficacy in lowering ICP after 4 h , with a secondary endpoint of the percentage of successfully treated episodes of intracranial hypertension . The analysis was performed with both intention-to-treat and actual treatments provided . Measurements and results Compared to mannitol , the effect of the lactate solution on ICP was significantly more pronounced ( 7 vs. 4 mmHg , P = 0.016 ) , more prolonged ( fourth-hour-ICP decrease : −5.9 ± 1 vs. −3.2 ± 0.9 mmHg , P = 0.009 ) and more frequently successful ( 90.4 vs. 70.4 % , P = 0.053 ) . Conclusion Acute infusion of a sodium lactate-based hyperosmolar solution is effective in treating intracranial hypertension following traumatic brain injury . This effect is significantly more pronounced than that of an equivalent osmotic load of mannitol . Additionally , in this specific group of patients , long-term outcome was better in terms of GOS in those receiving as compared to mannitol . Larger trials are warranted to confirm our findings BACKGROUND Steroids are used as adjuvant treatment in childhood pyogenic meningitis to attenuate host inflammatory responses to bacterial invasion . We aim ed to assess the effectiveness of dexamethasone in management of acute bacterial meningitis in a developing country . METHODS In a double-blind , placebo controlled trial , we included 598 children with pyogenic meningitis who had been admitted to the children 's wards of the Queen Elizabeth Central Hospital , Blantyre , Malawi . We did physical , neurological , developmental , and hearing assessment s at 1 and 6 months after discharge . The primary outcome was overall death . Secondary outcomes included sequelae , in-hospital deaths , and death after discharge . Analysis was done by intention to treat . FINDINGS Of the 598 included children , 307 ( 51 % ) were assigned to dexamethasone and 295 ( 49 % ) to placebo . 338 ( 40 % ) of 598 patients had Streptococcus pneumoniae , 170 ( 28 % ) Haemophilus influenzae type b , 66 ( 11 % ) Neisseria meningitidis , and 29 ( 5 % ) Salmonella spp . 78 ( 13 % ) patients had no growth on culture . The number of overall deaths was the same in the two treatment groups ( relative risk 1.00 [ 95 % CI 0.8 - 1.25 ] , p=0.93 ) . At final outcome , sequelae were identified in 84 ( 28 % ) of children on steroids and in 81 ( 28 % ) on placebo ( relative risk 0.99 [ 95 % CI 0.78 - 1.27 ] , p=0.97 ) . The number of children dying in hospital did not differ between groups . INTERPRETATION Steroids are not an effective adjuvant treatment in children with acute bacterial meningitis in developing countries Background and Purpose Hitherto , treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers . Methods We undertook a double-blind , stratified and r and omized , placebo-controlled clinical trial . Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited , provided computed tomography confirmed hemorrhage and informed consent was obtained . After stratification into alert , semicoma , and coma subgroups using the Glasgow Coma Scale , 107 patients received active treatment ( 500 ml of 10 % glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days ) and 109 were given corresponding saline treatment . Using a variety of objective scoring systems , patients were followed up for up to 6 months . Results At follow-up , all measures of outcome in the treated and control groups were very similar . At 6 months , respective mortality rates were 37 of 107 and 33 of 109 . Corresponding mean±SD improvements in Sc and inavian Stroke Study Group scores were 8.35±16.9 versus 11.55±15.6 ( long-term ) and 0.64±7.3 versus 2.40±6.9 ( prognostic ) , and improvements in the Barthel Index ratings were 10.72±24.7 versus 13.95±23.3 , respectively . Glasgow Coma Scale score improvements in the survivors were 0.81±1.5 and 1.16±1.7 in the treated and control groups , respectively . Hemolysis ( generally sub clinical ) was the only adverse effect of glycerol noted . Conclusions In the absence of any clinical ly or statistically significant difference in outcome between the treated and control groups , this trial provides no justification for glycerol therapy following acute cerebral Perfusion is thought to be impaired in brain edema due to reduced perfusion pressure . Brain edema therapy is assumed to improve perfusion . We assessed regional cerebral blood flow ( rCBF ) , regional cerebral blood volume ( rCBV ) and mean transit time of blood ( MTT ) using perfusion-weighted magnetic resonance imaging ( MRI ) in 15 patients showing acute local brain edema due to infa rct ion or intracerebral hematoma . Patients were treated by intravenous infusion of 125 ml 40 % sorbitol over 10 min . rCBF , rCBV and MTT in the edematous region were measured before and 30 min after treatment . Before treatment rCBF ( 46.5 + /- 12.1 vs. 42.9 + /- 10.5 ml 100 g-1 min-1 ) , MTT ( 4.7 + /- 1.9 vs. 4.0 + /- 1.7 s ) and rCBV ( 5.4 + /- 1.7 vs. 4.7 + /- 1.1 ml 100 g-1 ) were significantly ( p < 0.05 ) increased in the edematous region compared to the contralateral side . After treatment no significant differences could be found . We interpret the elevation of MTT and rCBV in the edema as signs of an autoregulative compensation of an impaired perfusion . rCBF is even over-compensated . After brain edema therapy perfusion seems normalised . This new MRI method appears as useful for measuring therapeutic effects on cerebral perfusion Background : Oral glycerol reduces severe neurologic sequelae in childhood bacterial meningitis , but the mechanism awaits elucidation . We conducted a prospect i ve , r and omized , double-blind study in which the effects of glycerol and intravenous dexamethasone were compared with placebo recipients in an intensive care setting in India . Methods : Thirty-six children at age 2 months to 12 years with meningitis were treated with ceftriaxone and were r and omized to receive also either dexamethasone intravenously , or glycerol orally , or both agents , or neither . The illness was monitored with preset criteria . The primary outcome measures were the changes in plasma osmolality and in urine output . Results : Nine children received glycerol , 8 dexamethasone , 11 both agents , and 8 only placebo . The leading agents identified were Streptococcus pneumoniae , Haemophilus influenzae type b , and Staphylococcus aureus . Only the glycerol recipients increased plasma osmolality by up to 3 % from the mean baseline of 294 mOsm/kg in the glycerol and 295 mOsm/kg in the glycerol-dexamethasone group . This change occurred within 6 hours , the critical period of treatment , and lasted < 24 hours . Blood pressure was not affected , nor did urine output increase . The dexamethasone-only and placebo-only recipients showed immediate decrease in serum osmolality . Conclusions : Because excretion of the cerebrospinal fluid is inversely associated with plasma osmolality , we suggest that the glycerol-induced osmolality increase reduce the volume of cerebrospinal fluid , enhanced water movement back to the plasma by osmosis , increased cerebral blood flow , and thus , improved brain oxygenation BACKGROUND It is uncertain whether all adults with bacterial meningitis benefit from treatment with adjunctive dexamethasone . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of dexamethasone in 435 patients over the age of 14 years who had suspected bacterial meningitis . The goal was to determine whether dexamethasone reduced the risk of death at 1 month and the risk of death or disability at 6 months . RESULTS A total of 217 patients were assigned to the dexamethasone group , and 218 to the placebo group . Bacterial meningitis was confirmed in 300 patients ( 69.0 % ) , probable meningitis was diagnosed in 123 patients ( 28.3 % ) , and an alternative diagnosis was made in 12 patients ( 2.8 % ) . An intention-to-treat analysis of all the patients showed that dexamethasone was not associated with a significant reduction in the risk of death at 1 month ( relative risk , 0.79 ; 95 % confidence interval [ CI ] , 0.45 to 1.39 ) or the risk of death or disability at 6 months ( odds ratio , 0.74 ; 95 % CI , 0.47 to 1.17 ) . In patients with confirmed bacterial meningitis , however , there was a significant reduction in the risk of death at 1 month ( relative risk , 0.43 ; 95 % CI , 0.20 to 0.94 ) and in the risk of death or disability at 6 months ( odds ratio , 0.56 ; 95 % CI , 0.32 to 0.98 ) . These effects were not found in patients with probable bacterial meningitis . Results of multivariate analysis indicated that dexamethasone treatment for patients with probable bacterial meningitis was significantly associated with an increased risk of death at 1 month , an observation that may be explained by cases of tuberculous meningitis in the treatment group . CONCLUSIONS Dexamethasone does not improve the outcome in all adolescents and adults with suspected bacterial meningitis ; a beneficial effect appears to be confined to patients with microbiologically proven disease , including those who have received prior treatment with antibiotics . ( Current Controlled Trials number , IS RCT N42986828 [ controlled-trials.com ] . ) |
2,369 | 17,925,636 | Heparin was reported to have a beneficial impact on mortality , graft and wound healing , and pain control .
Given poor study quality , there is no strong evidence to indicate that heparin can improve clinical outcomes in the treatment of burn injury . | This systematic review was conducted to assess the evidence for using heparin to treat burn injury . | BACKGROUND Heparin and direct thrombin inhibitors , such as hirudin , have limitations in the treatment of acute coronary syndromes . Heparin does not inactivate fibrin-bound thrombin , whereas hirudin fails to block thrombin generation . In contrast , Vasoflux is a novel anticoagulant that inactivates fibrin-bound thrombin and attenuates factor Xa generation . METHODS AND RESULTS Vasoflux is prepared by depolymerization of heparin , restricting molecular size to between 3000 and 8000 Da , and reducing antithrombin affinity by perio date oxidation . Vasoflux catalyzes fibrin-bound thrombin inactivation by heparin cofactor II ( HCII ) and inhibits factor IXa activation of factor X independently of antithrombin and HCII . Compared with other anticoagulants in a thrombogenic extracorporeal circuit , Vasoflux maintains filter patency at concentrations that produce an activated clotting time ( ACT ) of 220 seconds . In contrast , to maintain filter patency , heparin , low-molecular-weight heparin ( LMWH ) , and hirudin require concentrations that produced an ACT of 720 , 415 , and > 1500 seconds , respectively , whereas dermatan sulfate was ineffective at concentrations that produced an ACT of 360 seconds . CONCLUSIONS Vasoflux is more effective than heparin and LMWH because it inactivates fibrin-bound thrombin and is superior to hirudin and dermatan sulfate because it also blocks factor Xa generation |
2,370 | 22,175,545 | There was evidence that medical advice increased the success of quit attempts and inconclusive evidence that offering assistance increased their success .
CONCLUSIONS Physicians may be more effective in promoting attempts to stop smoking by offering assistance to all smokers than by advising smokers to quit and offering assistance only to those who express an interest in doing so | AIMS This study aim ed to assess the effects of opportunistic brief physician advice to stop smoking and offer of assistance on incidence of attempts to stop and quit success in smokers not selected by motivation to quit . | OBJECTIVES To assess general practitioners ' and practice nurses ' self reported behaviour , attitudes , and knowledge in relation to smoking cessation . DESIGN AND SETTING Two postal surveys of r and om national sample s of 303 GPs ( survey 1 ) and 459 practice nurses ( survey 2 ) covering Engl and and Wales ; effective response rates were 75 % and 96 % , respectively . RESULTS Survey 1 found that 96 % of GPs accepted that intervening against smoking was part of their role and almost all ( 99 % ) said that they recorded smoking status when patients registered ; 57 % reported that they routinely up date d their records on smoking status , 50 % said they advised smokers to stop during most or all consultations , and 76 % said they advised smokers to cut down if they can not stop . A large majority ( 83 % ) said they either recommended or prescribed nicotine replacement therapy ( NRT ) . Although most GPs ( 86 % ) thought that NRTs were effective , only a minority thought they were worth the cost ( 47 % ) or should be on National Health Service ( NHS ) prescription ( 32 % ) . There was little evidence that previous training in smoking cessation was associated with more activity , more positive attitudes , or greater knowledge . Survey 2 found that almost all practice nurses ( 99 % ) agreed that intervening against smoking was part of their role and 95 % said they advised patients to stop at least occasionally ; 71 % said they advised smokers to stop at most or all consultations . A majority ( 74 % ) said that they recommended NRT to their patients . As with the GPs most practice nurses thought that nicotine replacement was effective ( 79 % ) , but fewer ( 42 % ) thought the cost was justified , and only about half ( 53 % ) thought it should be available on NHS prescription . Nurses who said they had been trained in smoking cessation engaged in more activity relating to smoking cessation , had more positive attitudes , and were more knowledgeable . CONCLUSION GPs and practice nurses accepted that intervening with smoking was an important part of their role and a large majority reported that they intervened at least with some smokers . This represents a promising baseline from which to proceed in terms of implementation of the new smoking cessation guidelines , but it is hoped that improvements can be made in terms of the frequency of updating records and intervening , and acceptance of the cost-effectiveness of NRT as a life preserving intervention The efficacy of physician anti-smoking intervention with 289 patients in a family practice setting was assessed . The design included two treatment conditions , physician advice and physician advice plus the offer of nicotine chewing gum ( NCG ) prescription . A no-advice group permitted assessment of the effects of repeated testing . The NCG group had higher rates of abstinence at all follow-up points , but the difference approached statistical significance at 3 months only ( p less than .10 ) . Comparison of those who actually used NCG to all other groups revealed significantly more users were abstinent at 1- and 3-month follow-up . A similar pattern occurred for proportion attempting cessation and smoking reduction . A dose-response relationship of gum use to outcome was identified . Long-term users ( greater than 20 days ) had 86 % abstinence at 3 months versus 18 % for short-term users . Thus , NCG does appear to have a role in family practice for promoting short-term cessation Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly PURPOSE Guidelines encourage primary care clinicians to document smoking status when obtaining patients ’ blood pressure , temperature , and pulse rate ( vital signs ) , but whether this practice promotes cessation counseling is unclear . We examined whether the vital sign intervention influences patient-reported frequency and intensity of tobacco cessation counseling . METHODS This study was a cluster-r and omized , controlled trial conducted in the Virginia Ambulatory Care Outcomes Research Network ( ACORN ) . At intervention practice s , nurses and medical assistants were instructed to assess the tobacco use status of every adult patient and record it with the traditional vital signs . Control practice s did not use any systematic tobacco screening or identification system . Outcomes were the proportion of smokers reporting clinician counseling of any kind and the frequency of 2 counseling subcomponents : simple quit advice and more intensive discussion . RESULTS A total of 6,729 adult patients ( 1,149 smokers ) at 18 primary care practice s completed exit question naires during a 6-month comparison period . Among 561 smokers at intervention practice s , 61.9 % reported receiving any counseling , compared with 53.4 % of the 588 smokers at control practice s , for a difference of 8.6 % ( P = .04 ) . The effect was largely restricted to simple advice , which was reported by 59.9 % of intervention patients and 51.5 % of control patients ( P=.04 ) . There was no significant increase in more extensive discussion , with 32.5 % and 29.3 % of patients at intervention and control practice s , respectively , reporting this type of counseling ( P=.18 ) . CONCLUSIONS The vital sign intervention promotes tobacco counseling at primary care practice s through a modest increase in simple advice to quit . When implemented as a st and -alone intervention , it does not appear to increase intensive counseling BACKGROUND AND OBJECTIVE GPs are an important source of smoking cessation advice . This research examined whether a model encouraging GP referral of patients who smoke to a specialist service would be acceptable and effective for increased smoking cessation when compared with a model of in- practice management . METHODS The study design was cluster r and omized controlled trial . Practice s were r and omized to one of two interventions , at a rate of 1:2 : ( i ) st and ard in- practice GP management or ( ii ) referral to a quitline service . The main outcome measures were sustained abstinence of > or=1 month duration at 3-month follow-up and > or=10 months duration at 12 months , using intention to treat analysis . RESULTS At 3-month follow-up , patients in the referral condition were twice as likely to report sustained abstinence than those in the in- practice condition [ 12.3 % compared with 6.9 % ; odds ratio ( OR ) = 1.92 ( 95 % confidence interval ( CI ) 1.17 - 3.13 ] . At 12-month follow-up , patients in the referral condition had nearly three times the odds of sustained abstinence [ 6.5 % compared with 2.6 % ; OR = 2.86 ( 95 % CI 0.94 - 8.71 ) ] . The intervention effect was mediated by the amount of help received outside the practice . CONCLUSIONS This research provided evidence that GPs referring smokers to an evidence -based quitline service results in increased cessation . The benefit is largely due to patients in the referral condition receiving more external help than patients in the in- practice condition , as they received equivalent practice -based help . Where suitable services exist , we recommend that referral become the normative strategy for management of smoking cessation in general practice to complement any practice -based help provided The results are reported from a multicentered , r and omized clinical trial of a physician-delivered smoking cessation intervention package . All physicians attended a four-hour training session during which the rationale s for the different aspects of the intervention were discussed , including a detailed description of the proper use of nicotine-bearing chewing gum . Patients were r and omized to receive an offer of a prescription of 2 mg of nicotine chewing gum in addition to the basic intervention ( n = 111 ) or the basic intervention alone ( n = 112 ) . The basic intervention included advice , setting a date for quitting , self-help material s , and the offer of supportive follow-up visits . Receptionists were instructed to recruit the first two smokers attending the practice each day . One-year smoking cessation was vali date d by cotinine saliva analysis . The vali date d three-month sustained abstinence rates at one year were 8.1 percent and 9.8 percent in the gum and no-gum groups , respectively . The 95 percent confidence interval about this difference was -9.3 percent to 6.4 percent . There is no evidence from this study that the offer of 2 mg of nicotine-bearing gum enhances smoking cessation rates when added to a comprehensive intervention offered to all smokers in primary care . Until larger trials are completed , however , the possibility that this dose of nicotine gum may produce small beneficial effects can not be excluded BACKGROUND This project examined tobacco policies and delivery of cessation services in nonprofit HMOs that collectively provide comprehensive medical care to more than 8 million members . METHODS Three annual surveys with health plan managers showed that all of these health plans had written tobacco control guidelines that became more comprehensive over the span of this study . We also surveyed a r and om sample of 4207 current smokers who had attended a primary care visit in the past year ( 399 - 528 at each of nine health plans ) . RESULTS Of these smokers , 71 % reported advice to quit , 56 % were asked about their willingness to quit , 49 % were provided some assistance in quitting ( mostly self-help material or information about classes or counseling ) , and 9 % were offered some kind of follow-up . Smokers receiving assistance in quitting reported higher satisfaction with their care . CONCLUSIONS In general , health plans with the most comprehensive policies also showed higher rates of implementing tobacco treatment programs in primary care . Compared with tobacco control efforts of a decade or more ago , considerable progress has been made . However , there is still room for improvement in the proportion of smokers who receive the most effective forms of assistance in quitting The purpose of this study was to examine the effectiveness of different practice -based approaches to assist patients of primary care physicians to quit smoking and sustain cessation . Forty-four nonsmoking general practitioners volunteered for the study . After a period of training , they r and omized 923 smoking clients , unselected for motivation toward quitting , to four different intervention groups : ( i ) minimal intervention , consisting of one single counselling session and a brief h and out on quitting techniques ; ( ii ) repeated counselling including reinforcing sessions at Months 1 , 3 , 6 , and 9 ; ( iii ) repeated counselling and use of nicotine gum ; and ( iv ) repeated counselling and spirometry . Biochemically vali date d smoking status was assessed at six and 12 months after recruitment . The proportion of verified quitters at 12 months was 4.8 percent among subjects r and omized to the minimal intervention group , compared to 5.5 percent , 7.5 percent , and 6.5 percent among those r and omized to the three repeated-counselling groups . In no treatment group was the outcome significantly different from that for one-time counselling at the ( P<0.05 ) level . Lack of power , contamination , and low attendance at reinforcing sessions should be taken into account in interpreting the results Objective : To compare the characteristics of smokers who do and do not receive smoking cessation treatment in primary care . Design : Prospect i ve cohort study using practice s registered with the pilot Q RESEARCH data base . Setting : 156 550 patients aged 18 years and over from 39 general practice s located within four strategic health authorities , representing the former Trent Region , UK . Subjects : Patients registered with practice s between 1 April 2001 and 31 March 2003 aged 18 years and over who were identified as smokers before the two year study period . Outcome : Prescription for smoking cessation treatment ( nicotine replacement therapy ( NRT ) or bupropion ) in the two year study period . Variables : Age , sex , deprivation score , co-morbidity . Results : Of the 29 492 patients recorded as current smokers at the start of the study period 1892 ( 6.4 % ) were given prescriptions for smoking cessation treatment during the subsequent two years . Of these , 1378 ( 72.8 % ) were given NRT alone , 406 ( 21.5 % ) bupropion alone , and 108 ( 5.7 % ) both treatments . Smokers were more likely to receive smoking cessation treatment if they lived in the most deprived areas ( odds ratio ( OR ) for the most relative to the least deprived fifth , adjusted for sex , age , and co-morbidity , 1.50 , 95 % confidence interval ( CI ) 1.26 to 1.78 ) , and if they were aged 25–74 years compared to 18–24 years or 75 and over . Smokers with co-morbidity were also more likely to receive smoking cessation treatment . Smokers were less likely to receive smoking cessation treatment if they were male ( adjusted OR 0.68 , 95 % CI 0.62 to 0.75 ) . Conclusion : The low proportion of smokers being prescribed these products strongly suggests that a major public health opportunity to prevent smoking related illness is being missed Medical advice and use of nicotine gum have recently received increased attention as effective tools to encourage smokers to quit , yet the relative value of nurse vs physician counseling has not been explored in depth . In this study , 425 smokers attending three urban primary care centers in Barcelona were systematic ally allocated to one of three groups : group A patients received a brief counseling session to quit from their family physician ; group B patients were given the same brief counseling along with a free supply of nicotine gum ; group C received a brief health-education session from the primary care nurse . Three hundred forty-nine patients ( 82 % ) could be reached by telephone at the two-month follow up . By that time , after correcting for the estimated validity of the phone report of smoking status , the proportion declaring themselves to be nonsmokers was 10.9 % , 11.1 % , and 10.8 % , respectively , without significant differences between them . At one-year follow up the proportions were 4.4 % , 5.3 % , and 6.0 % . In the logistic regression analysis , only the expected difficulty of quitting was predictive of one-year abstention , OR = 3.1 ( 95 % CI : 1.3 - 7.3 ) . The present study shows no difference between physician versus nurse counseling and no improvement in the proportion of quitters with the addition of nicotine gum in the physician-counseled group This study was design ed to see whether the offer and prescription of nicotine chewing gum would enhance the efficacy of general practitioners ' advice to stop smoking . A sample of 1938 cigarette smokers who attended the surgeries of 34 general practitioners in six group practice s were assigned by week of attendance ( in a balanced design ) to one of three groups : ( a ) non-intervention controls , ( b ) advice plus booklet , and ( c ) advice plus booklet plus the offer of nicotine gum . Follow up was done after four months and one year . The results show a clear advantage for those offered the nicotine gum ( p less than 0.001 ) . After correction for those who refused or failed chemical validation and those who switched from cigarettes to a pipe or cigars , the proportions who were abstinent at four months and still abstinent at one year were 3.9 % , 4.1 % , and 8.8 % in the three groups , respectively . These percentages are based on all cigarette smokers who attended the surgeries including those who did not wish to stop and those in the gum group who did not try the gum ( 47 % ) . The effect of the offer and prescription of gum was to motivate more smokers to try to stop , to increase the success rate among those who tried , and to reduce the relapse rate of those who stopped . The self selected subgroup of 8 % who used more than one box of 105 pieces of gum achieved a success rate of 24 % . It would be feasible and effective for general practitioners to include the offer of nicotine gum and brief instructions on its use as part of a minimal intervention routine with all cigarette smokers . A general practitioner who adopts such a routine with similar success could expect to achieve about 35 - 40 long term ex-smokers a year and so save the lives of about 10 of them . If replicated by all general practitioners throughout the country the yield of ex-smokers would be about one million a year Objective : To assess the relative impacts of three physician-delivered smoking interventions in combination with follow-up contact from behavioral counselors . Design : R and omized controlled trial with pre-post measures of smoking rates . This paper reports six-month outcome data . Setting : Participants were recruited from among patients seen by 196 medical and family practice residents in five primary care clinics . Participants : Participants were 1,286 patients out of 1,946 eligible smokers approached . The patient group was 57 % female and 91 % white , had an average age of 35 years , and smoked , on average , slightly over one pack per day . Intervention : Physicians were trained to provide each of three interventions : advice only , brief patient-centered counseling , and counseling plus prescription of nicotine-containing gum ( Nicorette ™ ) . Half the patients received follow-up in the form of telephone counseling at three-monthly intervals from behavioral counselors . Measurements and main results : Changes in smoking behaviors were assessed by telephone interview six months after physician intervention . The differences in one-week point prevalence cessation rates among the physician interventions were significant ( p<0.01 ) : advice only , 9.1 % ; counseling , 11.9 % ; counseling plus gum , 17.4 % ; with no effect for telephone counseling . The time elapsed from physician encounter to initial quitting and the length of that period of abstinence also showed significant benefit of the counseling interventions . Patients receiving physician counseling were much more likely than those not receiving counseling to rate their physician as very helpful ( p<0.001 ) . Multiple regression analyses are also reported . Conclusion : Smoking intervention counseling provided by physicians is well received by patients and significantly increases the likelihood of cessation at six months , an effect that is augmented by the prescription of nicotine-containing gum , when compared with physician-delivered advice . Follow-up telephone counseling does not contribute significantly to smoking behavior changes The objective of this study was to evaluate the effect of a simple smoking intervention programme , carried out by a large number of general practitioners ( GPs ) among pregnant and non-pregnant women . Four groups of women were defined by the dichotomies pregnant versus non-pregnant and intervention versus control . The intervention was semistructured , using a flip-over and a booklet , and it was implemented in an ordinary sequence of consultations . The study involved 187 GPs in western Norway . The subjects were 350 daily smoking pregnant women and 274 daily smoking non-pregnant women , 18 - 34 years of age . The point prevalence abstinence rate at 18 months was 15 and 20 % for pregnant and non-pregnant women , respectively , in the intervention groups , and 7 % in the control groups ( Ppregnant = 0.06 , Pnon-pregnant = 0.006 ) . Twenty-five per cent of the pregnant women and 34 % of the non-pregnant women reported that they had reduced their cigarette consumption , but had not stopped smoking entirely . If we include all drop-outs as smokers , the continuous abstinence rate during 15 months was 6%/0 % among pregnant women ( intervention/control ) and 5%/1 % among non-pregnant women . Stopping smoking was associated with having a non-smoking partner ( P = 0.001 ) , and being encouraged to do so by their partner ( P = 0.004 ) . The prevalence of both pregnant and non-pregnant women who stopped smoking was higher in the intervention than in the control groups . Pregnant women stopped smoking as frequently as non-pregnant individuals . ( ABSTRACT TRUNCATED AT 250 WORDS Although many family physicians may discuss smoking cessation with their patients , few do so consistently . A common belief among many physicians is that such efforts will not deter their patients from smoking . Others believe the time commitment required for a successful intervention is excessive . The present study addressed the above issues by examining the effect of a 3- to 5-minute unstructured physician discussion encouraging smoking cessation with family practice patients . Cigarette-smoking patients of two busy family practice s in southeast Michigan were r and omly assigned to either a control group receiving routine care or an intervention group receiving , in addition to routine care , smoking cessation counseling from their physician . A third comparison group was drawn from smokers in practice s not involved in delivering the intervention . Two hundred thirty-eight patients from the intervention group , 178 from the control group , and 47 from the comparison group were followed up with a telephone interview at 6 months . Intervention group patients made significantly more quit attempts than did those in the control group ( P less than .001 ) , which was similar to the comparison group . At the 6-month follow-up , 8 % of intervention group members , and 4 % of both the comparison and control groups reportedly were abstinent from smoking . Among those contacted at the 1-year follow-up , the respective percentages abstinent were 8 % , 3 % , and 4 % . Although these differences in quit rates were not statistically significant , the findings suggest that physicians can positively affect patient smoking cessation . This intervention was feasible in busy family practice s , highlighting its generalizability and applicability to other family practice setting s in the United States A r and omized controlled trial was conducted to evaluate the efficacy of smoking cessation instruction given to general smokers at an annual physical examination . Four hundred and twenty-six male and 42 female clients were r and omly assigned to an intervention group ( I ) , and 413 males and 76 females were assigned to a control ( C ) group . The I group was given an approximately 2-minute smoking cessation instruction by physicians , answered a quiz concerning tobacco , chose their own behavioral goals and were h and ed a leaflet on how to quit smoking . Subjects in both groups responded to a self-administered question naire and a 6-month and 12-month follow-up was performed by post card or telephone . The I group received an encouragement card one month after instruction and abstainers of the I group were awarded a telephone card at the 6-month follow-up . The results were as follows : 1 ) The male I group exhibited 7.3 % ( 6 months ) , 10.1 % ( 12 months ) abstinence rates and the male C group 4.4 % ( 6 months ) , 5.3 % ( 12 months ) , respectively . The difference in 12-month abstinence rates was statistically significant . 2 ) The female I group exhibited abstinence rates of 16.7 % ( 6 months ) , 23.8 % ( 12 months ) and the female C group 14.5 % ( 6 months ) , 17.1 % ( 12 months ) , respectively . 3 ) A multivariate analysis of smoking cessation showed that lower nicotine dependency , strong determination for smoking cessation , and being female were significant factors for abstinence at the 6-month follow-up . At 12 months , the smoking cessation instruction also became a significant factor . These data suggest that a simple smoking cessation instruction at an annual physical examination was effective for general smokers OBJECTIVE To study physician-smoker interactions around the receipt of smoking cessation medication prescriptions to better underst and the low rates of reported assistance and follow-up . METHODS A stratified r and om sample of smokers recently filling prescriptions for cessation medications was identified for a phone interview about the quitting experience . The transcriptions of those portions of 50 interviews that addressed cessation contacts with clinicians were review ed by the co- authors and analyzed for quantifiable data , observations , and themes . RESULTS Although there were low levels of reported physician adherence to the Assist and Arrange recommendations of the Public Health Service 5As clinical guideline for smoking cessation , 27 ( 55 % ) of these smokers were quit at 1 to 3 months after the medication fill . Smoker descriptions of the contacts with their physicians about smoking cessation suggested nonconfrontational , collaborative , and satisfying interactions that were flexibly dominated by either party . Physician assistance predominantly concerned use of the medication ( 66 % ) . CONCLUSIONS These physician-smoker interactions seemed to be mutually accommodative . Given the apparent high quit rates and limited evidence of smoker interest in other forms of assistance , perhaps a physician-dominant encounter is not as common or as necessary as has been thought This study aim ed to test the hypothesis that people aged 60 and older respond to assistance in stopping smoking . Using a single general practitioner visit backed up by a practice nurse , 14 % of the smokers had discontinued the habit 6 months after the intervention period . The intervention group also showed some improvements in a st and ardized measure of breathlessness Three hundred and sixty-six patients volunteered for a smoking cessation trial and were r and omly allocated to a control group or to three interventions : a single counselling visit to a physician , eight sessions of group health education or eight sessions of group behavior modification . Progress was assessed by smoking diaries , supported by saliva thiocyanate tests , before and after the intervention and six and 12 months later . Only the two group approaches showed a significant improvement compared to the control group immediately after the intervention ; these differences were no longer statistically significant six or 12 months later . The group methods proved to be more cost-effective than the physician intervention . However , when different sub-groups were examined , such as heavy or light smokers , a different pattern of results emerged . For very heavy smokers , the physician-led intervention proved almost as successful as the group approaches . Overall quitting results were disappointing , but the programs appear to be more successful at helping people reduce smoking OBJECTIVES Several countries have followed the US example in publishing national guidelines on smoking cessation interventions . Gauging responses to these guidelines can provide important lessons for future implementation and revision internationally . This study sought to assess General Practitioners ' ( GPs ' ) views on recently published English smoking cessation guidelines that form the foundation of the UK National Health Service 's smoking cessation strategy . DESIGN Postal survey in which GPs were asked to judge the appropriateness , effectiveness and practicability of key recommendations for primary care in recent national smoking cessation guidelines . SETTING General practice , Engl and and Wales . SUBJECTS R and om national sample of GPs ; 236 GPs completed the question naire ; effective response rate : 62 % . RESULTS Only 16 % of GPs accepted that all the recommendations in the guidelines were appropriate ; 43 % accepted that it was appropriate to check the smoking status of known smokers when they visit the surgery and only 30 % thought it was practicable to advise smokers to stop at every opportunity . However , 77 % of GPs thought that they should provide assistance for smokers wanting to stop ; 74 % believed that they should refer smokers to specialist services if appropriate and a similar proportion ( 77 % ) believed that it was appropriate to recommend nicotine replacement therapy . CONCLUSIONS There was greater acceptance by GPs that they should assist smokers wanting to stop than that they should routinely monitor smoking status and give opportunistic advice to patients to stop . Given that opportunistic advice is a cornerstone of the national guidelines there is a need to find ways of reconciling what is being recommended and what GPs feel is appropriate OBJECTIVE --To evaluate a structured , behavioural change , smoking cessation intervention design ed for use within general practice . DESIGN --R and omised controlled clinical trial . SETTING --General practice s in Newcastle , Australia . PATIENTS --311 Patients identified as smokers by a screening question were enrolled in the study . Of these , 101 were assigned to a structured behavioural change programme , 104 to a simple advice programme adapted from previous research , and 106 to a control group . No significant differences were found between groups for demographic and smoking related variables before the study . INTERVENTIONS -- Patients in the simple advice group received a brief statement of advice from the general practitioner as well as three pamphlets ; those in the structured intervention group were given strategies which included attitude and behavioural change programmes as well as techniques to aid compliance . The amount of smoking in all groups was assessed by self reports with validation by measurement of salivary cotinine concentrations . MAIN OUTCOME MEASURE -- Significant increase in cessation rates . CONCLUSIONS --Significant differences between controls and the structured behavioural change group were found at the one month follow up , but only for self reported abstinence . The simple advice programme did not produce any significant differences over the control group . General practitioner evaluation of the structured programme highlighted difficulties in relation to the duration of the intervention . Overall the structured programme in its present form did not appear to be an effective programme for use within general practice BACKGROUND The purpose of this study was , to identify predictors of quitting following general practitioners ' ( GP ) anti-smoking counseling . METHODS We studied determinants ( characterized following the Precede framework ) of successful quitting ( 1 year sustained abstinence , biochemically confirmed at 6- and 12-month follow-up ) among 861 smokers r and omized to the intervention groups based on repeated counseling ( RC ) , RC + spirometric testing , and RC + nicotine gum , in a smoking cessation trial carried out in Turin , Italy . RESULTS GPs ' intervention worked best for male ( OR = 2.30 ; 95 % CI , 1.13 - 4.52 ) and married ( OR = 3.63 ; 95 % CI , 1.37 - 9.59 ) smokers , for smokers who had maintained abstinence for at least 1 month in the past ( OR = 6.78 ; 95 % CI , 1.56 - 29.52 ) or at their first quit attempt ( OR = 10.91 ; 95 % CI , 2.37 - 50.13 ) , and for those who spontaneously reduced their coffee consumption ( OR = 3.30 ; 95 % CI , 1.59 - 6.82 ) ; heavy smokers ( > = 20 cig/day OR = 0.48 ; 95 % CI , 0.24 - 0.93 ) and those living with other smokers ( > = 1 smokers in the household : OR = 0.44 ; 95 % CI , 0.22 - 0.90 ) were less likely to give up . Previous antismoking advice by the GP represented a strong barrier to success for healthy smokers ( OR = 0.19 ; 95 % CI , 0.07 - 0.52 ) , but not for those reporting symptoms of shortness of breath ( OR = 0.63 ; 95 % CI , 0.39 - 9.20 ) . There were no interactions between predictors and treatment conditions . CONCLUSIONS Assessment of factors influencing quitting would allow GPs to tailor their message to address existing barriers and to help patients utilize their re sources for change BACKGROUND In a population -based sample of smokers in early motivational stages , we found a high acceptance of smoking cessation groups . METHODS Inter99 is a r and omized population -based intervention study , in Copenhagen , Denmark . Smokers in all motivational stages were included . All participants underwent a lifestyle consultation and 2,168 smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups . RESULTS Thirty-five percent were vali date d to be continuously abstinent at the end of the smoking cessation groups . Eighty-four percent of the smokers achieving sustained abstinence in our study had no serious plans to quit soon before the lifestyle consultation . Motivation to quit before the lifestyle consultation could not predict abstinence . Being a man , and having a job and at least 1 year of vocational training were predictors of abstinence in a multivariate model , whereas high nicotine dependence and living with a smoking spouse were predictors of failure . CONCLUSION High cessation rates were obtained in a population of heavy smokers with moderate nicotine dependence . It was possible to obtain sustained abstinence in smokers in early motivational stages . These smokers would probably not have been reached by traditional smoking campaigns The results of a physician-based intervention on smoking done by general practitioners in Barcelona ( Spain ) are described one month and one year after its inception . Among the 208 smokers in the intervention group there were more attempts to quit , and they were more successful than in the 216 smokers in the control group . The proportions of quitters after a year was 5.3 % and 2.3 % in each group ( p less than 0.05 ) . Among the variables related to success in quitting are self-reliance , the willingness to reduce or quit smoking , the intensity of the habit and the family environment Of 6052 adult patients who consulted their doctors in six Oxfordshire general practice s between October 1980 and February 1981 , 2110 ( 35 % ) were smokers . The smokers were allocated to one of four study groups -- a control ( non-intervention ) group ; a group that received verbal and written antismoking advice from the general practitioner ; a group that received this advice and also a demonstration of exhaled carbon monoxide ; and a group that received the advice plus the offer of further help from a health visitor . After one year 72 % of smokers replied to a postal follow up question naire : 11 % of the control group cl aim ed to have stopped smoking compared with 15 % in the group that received advice alone , 17 % in the exhaled carbon monoxide group , and 13 % in the health visitor group . Validation of these findings by assays of urinary concentrations of cotinine showed that between 24 % and 40 % of subjects may have misreported their smoking habits , but there was no indication that the rate of misreporting was higher in the intervention groups than in the control group . Giving advice routinely against smoking has a useful effect , and showing an immediate , personal , and potentially harmful consequence of smoking using a CO-oximeter may improve this , particularly in lower socioeconomic groups BACKGROUND Lack of interest has been cited as a reason not to offer cessation assistance to smokers , but research suggests that smokers accept treatments offered proactively . This study assessed acceptability , utilization , and effectiveness of free smoking cessation treatment among diverse primary care patients . METHOD Medical assistants invited 4174 adult smokers to participate . Enrollees ( 1869 ) self-selected or were assigned to receive free nicotine patch therapy alone or in combination with the Committed Quitters(R ) program , and for some , individual counseling . RESULTS In nearly 68 % of cases , patients accepted a treatment invitation ; 77 % of eligible smokers enrolled ; 85 % of these picked up free patches . Given a choice of treatments , 75 % of participants elected a psychosocial treatment in addition to patch therapy . Thirteen percent of treatment initiators achieved biochemically confirmed 7-day point-prevalence abstinence at 1 year , with no significant treatment effects . Minority patients showed greater initial interest but less utilization did than White patients . CONCLUSIONS Free , readily accessible smoking cessation treatment offered in primary care setting s was accepted and used by the majority of unselected smokers of diverse racial/ethnic origins . Psychosocial treatment components did not significantly increase abstinence rates . Barriers , rather than lack of interest , may keep minority smokers from using cessation treatments |
2,371 | 21,549,010 | Evidence from r and omized controlled trials showed that case management improves function and appropriate use of medications , increases use of community services and reduces nursing home admission .
Evidence , mostly from non-r and omized trials , showed that integrated care increases service use ; r and omized trials reported that integrated care does not improve clinical outcomes .
The lowest quality evidence was for consumer directed care which appears to increase satisfaction with care and community service use but has little effect on clinical outcomes .
Conclusions The outcomes of each model of care differ and correspond to the model 's focus .
Combining key elements of all three models may maximize outcomes | Background Costs and consumer preference have led to a shift from the long-term institutional care of aged older people to home and community based care .
The aim of this review is to evaluate the outcomes of case managed , integrated or consumer directed home and community care services for older persons , including those with dementia . | CONTEXT Illness and hospitalization often trigger functional decline among older persons . Home care services implemented for functional decline provide an opportunity to intervene to improve outcomes . OBJECTIVE To compare functional status and the likelihood of remaining at home for persons receiving restorative care vs usual home care . DESIGN AND SETTING Intervention using prospect i ve individual matching conducted between November 1 , 1998 , and April 30 , 2000 . Six offices of a home care agency in Connecticut were used . One branch office served as the restorative care unit and the other 5 served as usual care offices . PARTICIPANTS Patients receiving home care through the restorative care office who were 65 years or older ; in receipt of Medicare-covered home care lasting at least 7 days ; with absence of severe cognitive impairment ; and not terminal , bedridden , or requiring total care were matched with patients from 1 of the usual care offices . The matching factors included age , sex , race , baseline self-care function , cognitive status , whether hospitalization preceded the home care episode , and date of the home care episode . Of the 712 eligible restorative care patients , 691 ( 97 % ) were matched with a usual care patient . INTERVENTION Restorative care , provided by the home care agency nursing , therapy , and home health aide staff , was based on principles from geriatric medicine , nursing , rehabilitation , and goal attainment . MAIN OUTCOME MEASURES Remaining at home , functional status at completion of the home care episode , and duration and intensity of home care episode . RESULTS Compared with usual care , and after adjusting for baseline characteristics and other factors , restorative care was associated with a greater likelihood of remaining at home ( 82 % vs 71 % ; odds ratio [ OR ] , 1.99 ; 95 % confidence interval [ CI ] , 1.47 - 2.69 ) and a reduced likelihood of visiting an emergency department ( 10 % vs 20 % ; OR , 0.44 ; 95 % CI , 0.32 - 0.61 ) . Home care episodes were shorter ( mean [ SD ] , 24.8 [ 26.8 ] days vs 34.3 [ 44.2 ] days ; S = -17 821 ; P<.001 ) . Restorative care patients had better mean ( SD ) scores than usual care patients in self-care ( 11.0 [ 2.1 ] vs 10.7 [ 2.5 ] ; P = .07 after adjustment ) , home management ( 9.5 [ 2.9 ] vs 9.2 [ 3.0 ] ; P = .05 after adjustment ) , and mobility ( 3.3 [ 0.8 ] vs 3.2 [ 0.9 ] ; P = .02 after adjustment ) . CONCLUSIONS This trial suggests that reorganizing the structure and goals of home care can enhance health outcomes of older patients without increasing health care utilization STUDY QUESTION Did the Medicare Alzheimer 's Disease Demonstration , with its goal of improving caregiver outcomes through case management and subsidized community services , affect the nursing home entry rate of treatments with dementia compared to controls ? DATA SOURCES Interviews conducted at baseline and six months thereafter . Measures include date of nursing home entry , client and caregiver health , and income . STUDY DESIGN The demonstration r and omly assigned voluntary applicants into treatment and control groups . Treatment group cases were eligible for case management and for an 80 percent discount on community care benefits , up to about $ 600 per month . DATA COLLECTION All cases received baseline and semi-annual assessment interviews for up to three years after enrollment . Analyses are among cases that remained in the demonstration for more than 30 days after enrollment ( n = 8,095 ) . PRINCIPAL FINDINGS The intervention of case management and subsidized community service had no effect on nursing home entry rates for treatments overall , compared to those of controls , and few effects on treatment subgroups , with the exception of one site where it may have increased nursing home entry rates . CONCLUSIONS Providing case management and subsidized community services with the goal of improving caregiver outcomes may have little effect on nursing home entry rates for people with dementia Objectives The aim was to evaluate the effects of integrated home care and discharge practice on the functional ability ( FA ) and health-related quality of life ( HRQoL ) of home care patients . Methods A cluster r and omised trial ( CRT ) with Finnish municipalities ( n=22 ) as the units of r and omisation . At baseline the sample included 669 patients aged 65 years or over . Data consisted of interviews ( at discharge , and at 3-week and 6-month follow-up ) , medical records and care registers . The intervention was a generic prototype of care/case management- practice ( IHCaD- practice ) that was tailored to municipalities needs . The aim of the intervention was to st and ardize practice s and make written agreements between hospitals and home care administrations , and also within home care and to name a care/case manager pair for each home care patient . The main outcomes were HRQoL — as measured by a combination of the Nottingham Health Profile ( NHP ) and the EQ-5D instrument for measuring health status— and also Activities of Daily Living ( ADL ) . All analyses were based on intention-to-treat . Results At baseline over half of the patient population perceived their FA and HRQoL as poor . At the 6-month follow-up there were no improvements in FA or in EQ-5D scores , and no differences between groups . In energy , sleep , and pain the NHP improved significantly in both groups at the 3-week and at 6-month follow-up with no differences between groups . In the 3-week follow-up , physical mobility was higher in the trial group . Conclusions Although the effects of the new practice did not improve the patients ' FA and HRQoL , except for physical mobility at the 3-week follow-up , the workers thought that the intervention worked in practice . The intervention st and ardised practice s and helped to integrate services . The intervention was focused on staff activities and through the changed activities also had an effect on patients . It takes many years to achieve permanent changes in every worker 's individual practice and it is also likely that changes in working practice s would be visible before effects on patients . The use of other outcome measures , such as the use of services , may be clearer in showing a positive impact of the intervention rather than FA or STUDY QUESTION Did the Medicare Alzheimer 's Disease Demonstration with its case management and community service waivers affect the use of community-based long-term care services among people with dementia and their primary caregivers ? DATA SOURCES Baseline and periodic caregiver interviews . Measures include client and caregiver attributes and self-reported service use . STUDY DESIGN The demonstration r and omly assigned voluntary applicants into treatment and control groups . Treatment group cases were eligible for case management and for up to $ 699 per month in community care benefits . The actual monthly entitlement varied among the eight demonstration communities due to regional cost and inflation adjustments over time . Analyses are for the year after enrollment . DATA COLLECTION Analyses are of cases surviving six months or more in the community after enrollment ( n = 5,209 ) . Cases received baseline and semi-annual assessment s. PRINCIPAL FINDINGS The intervention of case management and community service reimbursement had a strong , consistent , and positive effect on the likelihood of using home care ( including homemaker/chore services , personal care services , companion services ) and adult day care . Treatment group clients were at least twice as likely as control group clients to be using any of the four community-based services . A similar , but less pervasive effect was achieved with caregiver training and support group participation . Reimbursement provided by the demonstration 's Medicare waiver was generally not sufficient to exceed the level of control group service acquired through private payment . CONCLUSIONS Reimbursement levels within the demonstration may have enabled more individuals to purchase some services , but they were not sufficient to increase the average level of use over those in the control group . No consistent differences between demonstration models were found in service use likelihood or average use among users Abstract Objective : To evaluate the impact of a programme of integrated social and medical care among frail elderly people living in the community . Design : R and omised study with 1 year follow up . Setting : Town in northern Italy ( Rovereto ) . Subjects : 200 older people already receiving conventional community care services . Intervention : R and om allocation to an intervention group receiving integrated social and medical care and case management or to a control group receiving conventional care . Main outcome measures : Admission to an institution , use and costs of health services , variations in functional status . Results : Survival analysis showed that admission to hospital or nursing home in the intervention group occurred later and was less common than in controls ( hazard ratio 0.69 ; 95 % confidence interval 0.53 to 0.91 ) . Health services were used to the same extent , but control subjects received more frequent home visits by general practitioners . In the intervention group the estimated financial savings were in the order of £ 1125 ( $ 1800 ) per year of follow up . The intervention group had improved physical function ( activities of daily living score improved by 5.1 % v 13.0 % loss in controls ; P<0.001 ) . Decline of cognitive status ( measured by the short portable mental status question naire ) was also reduced ( 3.8 % v 9.4 % ; P<0.05 ) . Conclusion : Integrated social and medical care with case management programmes may provide a cost effective approach to reduce admission to institutions and functional decline in older people living in the community . Key messages Responsibility for management of care of elderly people living in the community is poorly defined Integration of medical and social services together with care management programmes would improve such care in the community In a comparison of this option with a traditional and fragmented model of community care the integrated care approach reduced admission to institutions and functional decline in frail elderly people living in the community and also reduced OBJECTIVE To examine how a new model of consumer-directed care changes the way that consumers with disabilities meet their personal care needs and , in turn , affects their well-being . STUDY SETTING Eligible Medicaid beneficiaries in Arkansas , Florida , and New Jersey volunteered to participate in the demonstration and were r and omly assigned to receive an allowance and direct their own Medicaid supportive services as Cash and Counseling consumers ( the treatment group ) or to rely on Medicaid services as usual ( the control group ) . The demonstration included elderly and non-elderly adults in all three states and children in Florida . DATA SOURCES Telephone interviews administered 9 months after r and om assignment . METHODS Outcomes for the treatment and control group were compared , using regression analysis to control for consumers ' baseline characteristics . PRINCIPAL FINDINGS Treatment group members were more likely to receive paid care , had greater satisfaction with their care , and had fewer unmet needs than control group members in nearly every state and age group . However , among the elderly in Florida , Cash and Counseling had little effect on these outcomes because so few treatment group members actually received the allowance . Within each state and age group , consumers were not more susceptible to adverse health outcomes or injuries under Cash and Counseling . CONCLUSIONS Cash and Counseling substantially improves the lives of Medicaid beneficiaries of all ages if consumers actually receive the allowance that the program offers OBJECTIVES To compare the effects of nurse case management with usual care provided to community-dwelling frail older people in regard to quality of life , satisfaction with care , functional status , admission to hospital , length of hospital stay , and readmission to emergency department . DESIGN R and omized controlled trial . SETTING University hospital and two proximal community health centers . PARTICIPANTS 427 frail older people ( > or = 70 years of age and at risk for repeated hospital admissions ) discharged home from the emergency department . INTERVENTIONS EXPERIMENTAL Nurse case management , which consisted of coordination and provision of healthcare services by nurses , both in and out of hospital , for a 10-month period . CONTROL Usual care , which varied by healthcare provider and community health center . MEASUREMENTS Outcomes were assessed 10 months post-r and omization by telephone and /or home interview and by medical record review . Question naires included the SF-36 , CSQ-8 , and OARS . RESULTS No significant differences were found in quality of life , satisfaction with care , functional status , admission to hospital , or length of hospital stay . Nurse-case-managed older adults were readmitted to the emergency department significantly more often than their usual care counterparts . CONCLUSIONS Frail older people receiving nurse case management are more likely to use emergency health services without a concomitant increase in health benefits Context Dementia is an incurable chronic disease , but assistance to caregivers can reduce the severity of patients ' symptoms and delay institutionalization . Because this assistance requires provision of multiple health care and social services , patients and caregivers might benefit from a coordinated system of care . Contribution The investigators r and omly assigned patients with dementia and their caregivers to usual care or to a coordinated system of care . In the coordinated system , care managers regularly assessed patient and caregiver pairs and coordinated guideline -recommended provision of services by health care providers and community agencies using computerized information systems . The study found that pairs cared for in the coordinated system received higher- quality health care and more needed assistance than those who received usual care . Caution s The study focused on a relatively homogeneous population of white , well-educated , otherwise healthy , noninstitutionalized patients with health insurance . The findings might not apply to other population s. Implication s The quality of care for patients with dementia and their caregivers can be improved with a model of care in which services provided by the health system and community agencies are coordinated by a care manager . The Editors Dementia has enormous health and financial consequences for affected individuals , their family caregivers , and society ( 15 ) . Although most dementia is currently neither preventable nor reversible , existing practice guidelines reflect evidence from r and omized , controlled trials that caregiver assistance and support can delay institutionalization ( 68 ) , and nonpharmacologic management of problem behaviors and depression can reduce symptom severity and improve patient health ( 9 , 10 ) . Yet , adherence to published dementia care guidelines ( 1114 ) is poor ( 15 ) , including inappropriate use of psychoactive medications for initial management of agitation ( 16 ) ; low referral rates to community agencies ( 17 , 18 ) ; and underdetection of elder abuse , for which cognitive impairment is a risk factor ( 19 ) , and of depression ( 20 ) , a common comorbid condition ( 21 ) . There are few controlled trials of improvement interventions for dementia care . An opinion leader intervention improved neurologists ' reported adherence to dementia care guidelines ( 18 ) , and a recent trial using advanced practice nurses within primary care improved care quality ( 22 ) ; other trials reported limited impacts ( 23 , 24 ) . All studies were conducted primarily within or outside of health care delivery systems ; to date , trials of comprehensive , guideline -based dementia care interventions that incorporate all chronic care model components , including substantive collaboration between health systems and community agencies ( 25 , 26 ) , have not been reported . Yet , this would seem to be a well-suited approach because of the multifaceted nature of dementia care management and the need for coordinated efforts across health care delivery systems and community agencies to provide recommended medical , behavioral , and social services and support . To address gaps in care quality for persons with dementia , we design ed and tested a guideline -based , comprehensive dementia care management intervention in a clinic-level , cluster r and omized , controlled trial ( 27 ) . Intervention components were based on the chronic care model and emphasized linkages with community re sources and multiagency coordination ( 25 , 26 , 28 ) . Key components included dementia care managers , formal procedures for communication within and between organizations and agencies , Internet-based care management , collaborative care planning with caregivers , caregiver self-management support , ongoing follow-up , and provider education . We hypothesized that patient and caregiver dyads in intervention clinics would receive care in higher accordance with guidelines ; receive more community re sources and services ; have fewer unmet caregiving assistance needs ; and have better patient and caregiver health and caregiving quality , social support , and perceived care quality than dyads receiving usual care . Methods The institutional review boards of the University of California , Los Angeles , and all participating health care organizations approved the study procedures . All enrolled patient and caregiver dyads provided written informed consent . Three health care organizations ( Kaiser Permanente San Diego , Scripps Clinic , University of California , San Diego , Healthcare ) and 3 community agencies ( Alzheimer 's AssociationSan Diego Chapter , Southern Caregiver Re source Center , Meals on WheelsGreater San Diego ) providing services for persons with dementia and their informal caregivers in the San Diego metropolitan area participated . Private group practice , academic group practice , and health maintenance organization practice types were represented by the 3 health care organizations . Study Participants The study included 18 clinics from the participating health care organizations ( 4 to 8 per organization ) ( Table 1 ) . The inclusion criterion was that these be primary care clinics . Table 1 . Characteristics of Participating Health Care Organizations * Patients with dementia who were age 65 years or older and receiving Medicare were identified by querying health care organization administrative data bases for occurrence during the previous year of a dementia diagnosis code ( 29 ) at an outpatient visit or hospitalization or a cholinesterase inhibitor prescription . Patient lists were grouped by primary provider and were circulated to those providers for confirmation of dementia diagnosis and identification of additional potential participants from his or her practice ( generating < 5 % of the sample ) . Patients had to have an informal caregiver ( age 18 years ) . Patients were recruited by mail with English- and Spanish- language letters from their physician and an opt-out postcard , followed by up to 3 mailings of a patient consent or assent form ( depending on the physician 's design ation of the patient 's ability to provide consent ) , a caregiver consent form ( containing a proxy consent for the patient if he or she was judged unable to provide consent ) , and a baseline caregiver survey . R and omization was conducted at the clinic level , based on the clinic-focused design of the care management intervention . Within each health care organization , we paired clinics by patient volume ; within each pair , we r and omly assigned 1 clinic to the intervention and the other clinic to usual care using a computerized r and om-number generator operated by a study statistician . Participants were unaware of clinic r and omization status at enrollment and at completion of the baseline survey and were not reminded of r and omization status at follow-up . Intervention A steering committee that included a physician from each health care organization , a leader from each community agency , a community caregiver , and investigators used a formal method ( 30 ) to identify 23 existing dementia guideline recommendations as care goals ( 11 , 12 , 14 ) . They also design ed a structured assessment , algorithms linking specific care management actions to assessment results , and interorganization care coordination and referral protocol s. A key intervention element was health care organization and community agencybased dementia care managers ( primarily social workers ) who received formal training and used an Internet-based care management software system for care planning and coordination ( 25 , 26 , 28 ) . Every enrolled patient and caregiver dyad in the intervention group was assigned 1 health care organization care manager , who contacted them to schedule a structured home assessment . Assessment responses were entered into the software system , generating a preliminary problem list and guides to care-plan actions . The care manager collaborated with the caregiver to prioritize problem areas ; teach problem-solving skills ; initiate care plan actions ; and send an assessment summary , a problem list , and selected recommendations to the patient 's primary care physician and other design ated providers . A menu of potential care plan actions ( for example , referral for respite care services ) was documented in a comprehensive care management manual . The care management protocol included ongoing follow-up , usually by telephone , with frequency based on need and a formal in-home re assessment every 6 months to assess the need for major care-plan revisions . The software system had a feature to enable efficient tracking of multiple cases and tasks . Referrals to a particular community agency were guided by flagged problem areas . With patient and caregiver consent , referrals were communicated through the software system to that agency , whose design ated care manager subsequently received system access to the assessment , problem list , and care plan . Each dyad could have 1 or more community agency care managers . Care managers from the health care organizations and community agencies received the same formal education and training program , which was conducted jointly , and met monthly to refine care coordination procedures . Care management began within a month after enrollment of the first dyads and was active throughout the study follow-up unless a case was closed , for example , because a patient moved out of the study area and no longer was enrolled in the health care organization . At each intervention clinic , more than 90 minutes of st and ardized , interactive seminars ( in up to 5 sessions ) on relevant care issues , including evaluation of acute behavioral changes , depression management , and determination of decision-making capacity ( 31 ) , were offered to primary care providers . Selected intervention tools and documents with more detailed descriptions can be accessed at www.adc.ucla.edu/access/access.swf . Patients , caregivers , and providers in the usual care group were not offered study interventions . Outcome Measures Primary Outcome The study 's primary outcome was PURPOSE This study examined the effects of an early interventive social service program on the subjective well-being , permanent institutionalization , and mortality risk of low-income community-dwelling elders . DESIGN AND METHODS From a waiting list for community-based services , 105 " moderately at-risk " community-dwelling elders were recruited . Forty of these persons were r and omly assigned to receive the intervention , and the remainder did not receive the intervention . Participants were interviewed every 3 months for 18 months . Primary outcome measures were depression , satisfaction with social relationships , environmental mastery , life satisfaction , permanent institutionalization , and mortality . RESULTS No significant differences in sociodemographic or health characteristics were found between the intervention and control groups at baseline . Those elders who received the intervention had significantly higher subjective well-being and were less likely to be institutionalized or die than those in the comparison group across the 18-month period . IMPLICATION S The results make a strong case for the importance of community-based programs to the well-being of elders . Practitioners and policy makers should continue the search for community-based programs that are cost-effective and improve the quality of life for elders PURPOSE To investigate the prevalence of underpowered r and omized controlled trials ( RCTs ) presented at American Society of Clinical Oncology ( ASCO ) annual meetings . METHODS We surveyed all two-arm phase III RCTs presented at ASCO annual meetings from 1995 to 2003 for which negative results were obtained . Post hoc calculations were performed using a power of 80 % and an alpha level of .05 ( two sided ) to determine sample sizes required to detect small , medium , and large effect sizes . For studies reporting a proportion or time-to-event as primary end point , effect size was expressed as an odds ratio ( OR ) or hazard ratio ( HR ) , respectively , with a small effect size defined as OR/HR > or= 1.3 , medium effect size defined as OR/HR > or= 1.5 , and large effect size defined as OR/HR > or= 2.0 . Logistic regression was used to identify factors associated with lack of statistical power . RESULTS Of 423 negative RCTs for which post hoc sample size calculations could be performed , 45 ( 10.6 % ) , 138 ( 32.6 % ) , and 233 ( 55.1 % ) had adequate sample size to detect small , medium , and large effect sizes , respectively . Only 35 negative RCTs ( 7.1 % ) reported a reason for inadequate sample size . In a multivariable model , studies that were presented at oral sessions ( P = .0038 ) , multicenter studies supported by a cooperative group ( P < .0001 ) , and studies with time to event as primary outcome ( P < .0001 ) were more likely to have adequate sample size . CONCLUSION More than half of negative RCTs presented at ASCO annual meetings do not have an adequate sample to detect a medium-size treatment effect The Home Independence Program ( HIP ) is a short-term restorative programme targeted at older home-care clients , who do not have a diagnosis of dementia , when they are first referred for assistance or when they are referred for additional services because their needs have increased . This study compared the outcomes for individuals who participated in HIP with those of individuals who received ' usual ' home-care services . The study was conducted in metropolitan Perth , Western Australia , between 2001 and 2003 , when HIP was being trialled as a service in just one region . One hundred clients were recruited into each group and were visited at home on three occasions -- service start and at 3 months and 1 year . St and ardised outcome measures were used to measure functional dependency , morale , confidence in performing everyday activities without falling and functional mobility . Service outcomes were also examined at 3 months and 1 year . The HIP group showed improvements on all personal outcome measures compared with the control group . These improvements were , except for the morale scale , significantly associated with group assignment even when baseline differences between the groups were adjusted for . As regards service outcomes , the odds of the individuals who received HIP still requiring services was 0.07 ( 95 % CI = 0.03 - 0.15 , P < 0.001 ) times those for the individuals in the control group at 3 months and 0.14 times at 12 months ( 95 % CI = 0.07 - 0.29 , P < 0.001 ) . The results of this study supported the hypothesis that older individuals referred for home care who participated in a programme to promote their independence had better individual and service outcomes than individuals who received usual home care OBJECTIVE To examine the service experiences and outcomes of low-income Medicaid beneficiaries with disabilities under two different models for organizing home-based personal assistance services : agency-directed and consumer-directed . DATA SOURCE A survey of a r and om sample of 1,095 clients , age 18 and over , who receive services in California 's In-Home Supportive Services ( IHSS ) program funded primarily by Medicaid . Other data were obtained from the California Management and Payrolling System ( CMIPS ) . STUDY DESIGN The sample was stratified by service model ( agency-directed or consumer-directed ) , client age ( over or under age 65 ) , and severity . Data were collected on client demographics , condition/functional status , and supportive service experience . Outcome measures were developed in three areas : safety , unmet need , and service satisfaction . Factor analysis was used to reduce multiple outcome measures to nine dimensions . Multiple regression analysis was used to assess the effect of service model on each outcome dimension , taking into account the client-provider relationship , client demographics , and case mix . DATA COLLECTION Recipients of IHSS services as of mid-1996 were interviewed by telephone . The survey was conducted in late 1996 and early 1997 . PRINCIPAL FINDINGS On various outcomes , recipients in the consumer-directed model report more positive outcomes than those in the agency model , or they report no difference . Statistically significant differences emerge on recipient safety , unmet needs , and service satisfaction . A family member present as a paid provider is also associated with more positive reported outcomes within the consumer-directed model , but model differences persist even when this is taken into account . Although both models have strengths and weaknesses , from a recipient perspective the consumer-directed model is associated with more positive outcomes . CONCLUSIONS Although health professionals have expressed concerns about the capacity of consumer direction to assure quality , particularly with respect to safety , meeting unmet needs , and technical quality , our findings suggest that the consumer-directed service model is a viable alternative to the agency model . Because public programs are under growing pressure to address the long-term care needs of low-income people of all ages with disabilities , the Medicaid personal assistance benefit needs to be reassessed in light of these findings . Consumer-directed models may offer a less elaborate and possibly less costly option for organizing supportive services at home . Study limitations may limit the generalizability of these findings . This was a natural experiment , in which only some counties offered both service models and counties assigned recipients to a service model . The use of a telephone survey excluded important recipient subsets , notably people with severe cognitive impairments . A more definitive study would include direct observations as well as survey approaches PURPOSE To evaluate the clinical outcomes of a nurse care coordination program for people receiving services from a state-funded home and community-based waiver program called Missouri Care Options ( MCO ) . DESIGN A quasi-experimental design was used to compare 55 MCO clients who received nurse care coordination ( NCC ) and 30 clients who received MCO services but no nurse care coordination . METHODS Nurse care coordination consists of the assignment of a registered nurse who provides home care services for both the MCO program and Medicare home health services . Two st and ardized data sets , the Minimum Data Set ( MDS ) for resident care and planning and the Outcome Assessment Instrument and Data Set ( OASIS ) were collected at baseline , 6 months , and 12 months on both groups . Cognition was measured with the MDS Cognitive Performance Scale ( CPS ) , activities of daily living ( ADL ) as the sum of five MDS ADL items , depression with the MDS-Depression Rating Scale , and incontinence and pressure ulcers with specific MDS items . Three OASIS items were used to measure pain , dyspnea , and medication management . The Cochran-Mantel-Haenszel ( CMH ) method was used to test the association between the NCC intervention and clinical outcomes . FINDINGS At 12 months the NCC group scored significantly better statistically in the clinical outcomes of pain , dyspnea , and ADLs . No significant differences between groups were found in eight clinical outcome measures at 6 months . CONCLUSIONS Use of nurse care coordination for acute and chronic home care warrants further evaluation as a treatment approach for chronically ill older adults OBJECTIVES To determine whether a telephone care-management intervention for high-risk Medicare health maintenance organization ( HMO ) health plan enrollees can reduce costly medical service utilization . DESIGN R and omized , controlled trial measuring healthcare services utilization over three 12-month periods ( pre- , during , and postintervention ) . SETTING Two social service organizations partnered with a Medicare HMO and four contracted medical groups in southern California . PARTICIPANTS Eight hundred twenty-three patients aged 65 and older ; eligibility was determined using an algorithm to target older adults with high use of insured healthcare services . INTERVENTION After assessment , members in the intervention group were offered mutually agreed upon referrals to home- and community-based services ( HCBS ) , medical groups , or Medicare HMO health plan and followed monthly for 1 year . MEASUREMENTS Insured medical service utilization was measured across three 12-month periods . Acceptance and utilization of Care Advocate ( CA ) referrals were measured during the 12-month intervention period . RESULTS CA intervention members were significantly more likely than controls to use primary care physician services ( odds ratio (OR)=2.05 , P<.001 ) , and number of hospital admissions ( OR=0.43 , P<.01 ) and hospital days ( OR=0.39 , P<.05 ) were significantly more stable for CA group members than for controls . CONCLUSION Results suggest that a modest intervention linking older adults to HCBS may have important cost-saving implication s for HMOs serving community-dwelling older adults with high healthcare service utilization . Future studies , using a national sample , should verify the role of telephone care management in reducing the use of costly medical services OBJECTIVE This analysis evaluated mortality over 24 months for Medicare managed care members who participated in the Care Advocate Program ( CA Program ) design ed to link those with high health care utilization to home- and community-based services . DATA SOURCE Secondary data from the CA Program , part of the California HealthCare Foundation 's Elders in Managed Care Initiative . STUDY DESIGN R and omized-control trial in which participants ( N=781 ) were r and omly assigned to intent-to-treat ( ITT ) and control groups . ITT group received telephonic social care management and 12 months of follow-up . Various multivariate analyses were used to evaluate mortality risk throughout multiple study periods controlling for sociodemographic characteristics , health status , and health care utilization . POPULATION STUDIED Older adults ( 65 + ) enrolled in a Medicare managed care plan who had high health care utilization in the previous year . PRINCIPAL FINDINGS ITT group had a significantly lower odds of mortality throughout the study ( OR=0.55 ; p=.005 ) and during the care management intervention ( OR=0.45 ; p=.006 ) , whereas differential risk in the postintervention period was not statistically significant . Other significant predictors of mortality were age , gender , three chronic conditions ( cancer , heart disease , and kidney disease ) , and emergency room utilization . CONCLUSIONS Findings suggest that the care advocate model of social care management affected mortality while the program was in progress , but not after completion of the intervention phase . Key model elements accounted for the findings , which include individualized targeting , assessment , and monitoring ; consumer choice , control , and participant self-management ; and bridging medical and social service delivery systems through direct linkages and communication PURPOSE We describe the impact of two interventions , a consumer-directed voucher for in-home supportive services and a chronic disease self-management-health-promotion nurse intervention , on the probability of use of two types of home care-skilled home health care and personal assistance services-received by functionally impaired Medicare beneficiaries . DESIGN AND METHODS The Medicare Primary and Consumer-Directed Care Demonstration was a r and omized controlled trial in 19 counties in New York , West Virginia , and Ohio with four groups : disease-management-health-promotion nurse , consumer-directed voucher , combination ( nurse plus voucher ) , and control . We estimated a bivariate probit model for the 1,394 individuals aged 65 or older who had no private long-term-care insurance . RESULTS Whereas the nurse intervention alone had no effect on the probability of using either type of home care , the voucher alone increased the probability of personal assistance services use by 13 % ( p = .002 ) but not that of skilled home health care use . The combination of the two interventions increased the probability of personal assistance services use by 18 % ( p < .001 ) . IMPLICATION S The implementation of disease-management-health-promotion nurse interventions should not lead to a greater probability of skilled home health care or personal assistance services use , whereas the provision of consumer-directed vouchers should result in an increased probability of personal assistance services use , as intended STUDY QUESTION Does improved access to community-based care reduce perceived burden and reported levels of depression among primary caregivers of people with dementia ? DATA SOURCES Baseline and periodic caregiver interviews with participants in the Medicare Alzheimer 's Disease Demonstration . Client and caregiver attributes and caregiver outcomes such as depression and burden scores were among the measures . STUDY DESIGN Applicants to the demonstration ( all voluntary ) were r and omly assigned into treatment and control groups . Treatment group cases were eligible for case management and for up to $ 699 per month in community care benefits . ( The actual monthly entitlement varied among the eight demonstration communities due to regional cost differences and inflation adjustments over the four-year demonstration period . ) DATA COLLECTION A total of 5,307 eligible individuals received a baseline assessment at the time of application to the demonstration and at least one semi-annual re assessment . Clients and their caregivers were periodically reassessed producing a total of 20,707 observations . PRINCIPAL FINDINGS Persons in the treatment group had a high exposure to case management and a greater likelihood of community service use relative to those in the control group . Treatment group membership was associated with statistically significant , but very small reductions in caregiver burden ( in four of eight sites ) and depression ( three of eight sites ) over a 36-month tracking period . These findings are not sustained with all cases combined , or among a higher-re source demonstration model considered separately . CONCLUSIONS Both the fact that these programmatic differences did not translate into substantial treatment group reductions in caregiver burden or depression , and the consistency of these findings with those of prior case management evaluations suggest the need to reformulate this programmatic intervention into areas not previously tested : 24-hour care , crisis intervention , coordination with primary care , or chronic disease management Background . It has not been demonstrated that the implementation of computerized quality improvement strategies can improve client-centered outcomes in public community based , long-term care ( CBLTC ) programs . Objectives . To test and evaluate 2 innovative computer-assisted , client-centered quality improvement strategies for public community-based , long-term care . The first strategy , the Normative Treatment Planning ( NTP ) program , assesses needs , prescribes services , and evaluates outcomes . The second strategy , the Client Feedback System ( CFS ) program , provides service vendors with feedback on client perceptions of services . Research Design . A 2 × 2 factorial design with the 2 strategies using cluster r and omization . Subjects . A total of 2222 clients ( 86 % of eligible program clients ) enrolled in Indiana ’s state case management program and /or the Medicaid home and community-based services waiver program for the aged and disabled as of January 1 , 1995 . Measures . Outcomes of needs met and client satisfaction were measured through telephone surveys every 6 months for 2 years . Results . A total of 1006 participants ( 45 % ) completed the 2-year evaluation study . For the group using only the NTP program , perception of needs met and client satisfaction were significantly better than the control group over the 2 years . During this period , the group using only the CFS program had significantly better client satisfaction than the control group . However , the effect sizes of the significant differences were small , and no statistically significant effects were found for the group using both programs . Conclusions . Client-centered quality improvement strategies can be implemented to enable public CBLTC programs to meet client needs better and increase client satisfaction OBJECTIVES To determine whether community care of demented patients can be prolonged by means of a 2-year support program based on nurse case management . DESIGN R and omized controlled intervention study with 2-year follow-up . SETTING Demented patients entitled to payments from the Social Insurance Institution for community care , in five municipalities in eastern Finl and . PARTICIPANTS One hundred demented patients , age 65 and older , living at home with the primary support of informal caregivers , allocated at r and om to the intervention ( n = 53 ) or control group ( n = 47 ) . INTERVENTION Intervention patients and their caregivers were provided with a 2-year intervention program of systematic , comprehensive support by a dementia family care coordinator . MEASUREMENTS Time to institutionalization ( period in community care ) from enrollment of patients in the study to their placement in long-term institutional care . RESULTS During the first months , the rate of institutionalization was significantly lower in the intervention group than in the control group ( P = .042 ) , but the benefit of the intervention decreased with time ( P = .028 ) . Estimated probability of staying in community care up to 6 , 12 , and 24 months was 0.98 , 0.92 , and 0.63 in the intervention group and 0.91 , 0.81 , and 0.68 in the control group , respectively . Results also suggest that the intervention used in the study might be especially beneficial to patients with severe dementia and those with problems threatening the continuity of community care . CONCLUSIONS The placement of demented patients in long-term institutional care can be deferred with the support of a dementia family care coordinator . However , by the end of the 2-year intervention , the number of patients institutionalized was similar in the intervention and control group . It seems to be beneficial to direct this type of intensive support at severely demented patients and their caregivers . On the basis of our experiences , we suggest that intervention by a dementia family care coordinator should be targeted especially at patients with problems threatening the continuity of community care |
2,372 | 27,943,261 | There were little or no differences in the primary outcomes for patients who were concurrently receiving treatment for tuberculosis .
Authors ' conclusions Both drugs have similar benefits in initial treatment of HIV infection when combined with two NRTIs .
The adverse events encountered affect different systems , with EFV more likely to cause central nervous system adverse events and NVP more likely to raise transaminases , cause neutropenia and rash . | Abstract Background The advent of highly active antiretroviral therapy ( ART ) has reduced the morbidity and mortality due to HIV infection .
The World Health Organization ( WHO ) ART guidelines focus on three classes of antiretroviral drugs , namely nucleoside or nucleotide reverse transcriptase inhibitors ( NRTI ) , non‐nucleoside reverse transcriptase inhibitors ( NNRTI ) and protease inhibitors .
Two of the most common medications given as first‐line treatment are the NNRTIs , efavirenz ( EFV ) and nevirapine ( NVP ) .
It is unclear which NNRTI is more efficacious for initial therapy .
This systematic review was first published in 2010 .
Objectives To determine which non‐nucleoside reverse transcriptase inhibitor , either EFV or NVP , is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children . | ABSTRACT Background Patients infected with HIV-1 initiating antiretroviral therapy ( ART ) containing a non-nucleoside reverse transcriptase inhibitor ( NNRTI ) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor . We analysed whether lipid changes differed between the two most commonly used NNRTIs , nevirapine ( NVP ) and efavirenz ( EFV ) . Methods and Findings Prospect i ve analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up . Patients were allocated to NVP ( n = 417 ) , or EFV ( n = 289 ) in combination with stavudine and lamivudine . The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol ( HDL-c ) , total cholesterol ( TC ) , TC : HDL-c ratio , non-HDL-c , low-density lipoprotein cholesterol , and triglycerides . The increase of HDL-c was significantly larger for patients receiving NVP ( 42.5 % ) than for patients receiving EFV ( 33.7 % ; p = 0.036 ) , while the increase in TC was lower ( 26.9 % and 31.1 % , respectively ; p = 0.073 ) , result ing in a decrease of the TC : HDL-c ratio for patients receiving NVP ( −4.1 % ) and an increase for patients receiving EFV ( + 5.9 % ; p < 0.001 ) . The increase of non-HDL-c was smaller for patients receiving NVP ( 24.7 % ) than for patients receiving EFV ( 33.6 % ; p = 0.007 ) , as were the increases of triglycerides ( 20.1 % and 49.0 % , respectively ; p < 0.001 ) and low-density lipoprotein cholesterol ( 35.0 % and 40.0 % , respectively ; p = 0.378 ) . These differences remained , or even increased , after adjusting for changes in HIV-1 RNA and CD4 + cell levels , indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection . The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs . Conclusion NVP-containing ART shows larger increases in HDL-c and decreases in TC : HDL-c ratio than an EFV-containing regimen . Based on these findings , protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor , particularly those containing NVP , may be expected to result in a reduced risk of coronary heart disease OBJECTIVE This prospect i ve , observational , study evaluates the clinical outcomes , drug utilization patterns , and adherence to treatment of patients on highly active anti retroviral therapy ( HAART ) at a government institution in Kerala , India . METHODS Patients who met criteria for treatment of HIV/AIDS were enrolled into the study , given free NNRTI-based combination therapy , and were followed for a period of 6 months . Data regarding demographics , clinical outcome , laboratory results , drug utilization , adherence and adverse effects were collected . Analysis was conducted utilizing descriptive statistics , anova , Fisher-exact , and t-test . RESULTS One hundred and forty-two patients with HIV-1 were enrolled in the study into three treatment groups . The mean age was 37.88 years , 64 % of the patients were male , and 92 % were married . Group 1 was given zidovudine , lamivudine , and nevirapine [ n = 52 ( 37 % ) ] , group 2 was given lamivudine , stavudine , and nevirapine [ n = 51 ( 36 % ) ] , and group 3 was given lamivudine , stavudine , and efavirenz [ n = 39 ( 27 % ) ] . The increase in CD4 was 107.46 ( SD : 106.25 ) . Mean medication adherence for the 104 patients who completed the study , was 90.7 % ; for group 1 : 92.06 % , group 2 : 93.37%1 , and group 3 : 85.71 % ( P > 0.05 ) . Forty ( 38 % ) patients have at least one adverse event to HARRT , with headache being the most common side effect ( 11.5 % ) . Mortality rate was 3.5 % during the course of the study . CONCLUSION Provision of free NNRTI-based combination therapy to patients in Kerala , India , result ed in greater than 90 % adherence leading to better clinical outcomes in terms of increasing CD4 counts and low mortality , for patients consistently attending a treatment clinic Objectives : We wished to determine the efficacy of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in antiretroviral-naive patients commencing highly active antiretroviral therapy ( HAART ) and to evaluate the effect of calendar year , nucleoside analogue reverse transcriptase inhibitor ( NRTI ) backbone , sex , and ethnicity on treatment outcome . Methods : Antiretroviral-naive individuals commencing efavirenz or nevirapine with dual-nucleoside analogue backbones were identified from a prospect i ve data base . Virological success was defined as HIV viral load < 500 copies per milliliter . Treatment failure was defined as a switch or discontinuation of NNRTI or documented virological failure ( 2 measurements with viral load > 500 copies/mL ) . Results : From a cohort of 994 individuals , 73 % commenced efavirenz- and 27 % nevirapine-containing regimens . We found no differences between the 2 treatment groups for the time to virological success ( proportion with virological success : efavirenz 71 % , nevirapine 72 % , P = 0.77 ) or treatment failure ( proportion failing treatment : efavirenz 23 % , nevirapine 26 % , P = 0.58 ) . There was a significant difference in the calendar year for commencing HAART for the time to virological success and treatment failure ( P < 0.001 ) . In the multivariable model , the likelihood of virological success for stavudine/lamivudine was 52 % [ relative hazard ( RH ) 1.52 , 95 % confidence interval ( CI ) 1.17 to 1.97 , P = 0.002 ] . The nonthymidine analogue backbones as a group seemed to be least likely associated with virological success ( RH 0.62 , 95 % CI 0.48 to 0.80 , P < 0.001 ) . This was however largely driven by tenofovir/didanosine being significantly associated with treatment failure ( RH 6.48 , 95 % CI 3.81 to 11.0 , P < 0.001 ) . Sex and ethnicity were not associated with treatment outcome . Conclusions : We found no significant differences between nevirapine and efavirenz for the time to virological success or treatment failure . Calendar year of commencing HAART and NRTI backbones were significant predictors of virological success and treatment failure , explaining differences in data to the 2NN study . The weaker the NNRTI ( or the weaker the protease inhibitor ) the more important the NRTI backbone becomes Objectives and Design We used data from a r and omized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome ( IRIS ) occurring within 12 weeks of starting antiretroviral therapy , and to evaluate its association with patient outcome at 48 weeks . Methods HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were r and omized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment , and were then followed for 48 weeks . Tuberculosis cases were diagnosed using WHO guidelines , and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS . Results The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm3 and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1 % ( 35/573 ) . Fifty-three ( 9.2 % ) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy . Being female and having a low CD4 count , high HIV-1 RNA load , low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS . After adjustment for baseline body mass index , CD4 count and hemoglobin , occurrence of tuberculosis-IRIS was independently associated with 48-week mortality ( aOR 2.72 95%CI 1.14 - 6.54 ) . Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS . Conclusion In this large prospect i ve cohort , tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation OBJECTIVE The relationships between adverse events ( AEs ) and plasma concentrations of nevirapine ( NVP ) and efavirenz ( EFV ) were investigated as part of the large , international , r and omized 2NN study . METHODS Treatment-naive , HIV-1-infected patients received NVP ( once or twice daily ) , EFV or their combination , each in combination with lamivudine and stavudine . Blood sample s were collected on day 3 and weeks 1 , 2 , 4 , 24 and 48 . Concentrations of NVP and EFV were quantitatively assessed by a vali date d HPLC assay . Individual Bayesian estimates of the area under the plasma concentration-time curve over 24 h ( AUC24h ) , and minimum and maximum plasma concentrations ( Cmin and Cmax ) as measures for drug exposure of NVP and EFV , were generated using a previously developed population pharmacokinetic model . Pharmacokinetic parameters were compared for patients with and without central nervous system ( CNS ) and psychiatric AEs , hepatic events , liver enzyme elevations ( LEEs ) and rash . Furthermore , it was investigated whether a clear cut-off for a pharmacokinetic parameter could be identified above which the incidence of AEs was clearly increased . AEs were also related to demographic parameters and baseline characteristics . RESULTS In total , from 1077 patients , NVP ( 3024 sample s ) and EFV ( 1694 sample s ) plasma concentrations and AE data ( 825 observations ) were available . For all patients Cmin , Cmax and AUC24h were determined . When corrected for known covariates of gender , CD4 cell count at baseline , region , hepatitis coinfection and possible interactions between these factors , no significant associations between AEs and any tested exposure parameter of NVP was observed . Also , no target Cmin value , above which patients were at increased risk for AEs , could be established . On the other h and , geographical region , hepatitis coinfection , CD4 cell count and gender were found to be significantly related with the incidence of CNS and psychiatric AEs , hepatic events , LEEs and rash during the treatment with NVP . The occurrence of elevated liver enzymes during the first 6 weeks in the EFV-containing arm was significantly ( P = 0.036 ) correlated to the exposure of EFV ( Cmin ) . Only hepatitis coinfection impacted on LEEs during the first 6 weeks of treatment . With an EFV Cmin above 2.18 mg/l during the induction phase , patients were 4.4 ( range 1.3 - 15.5 ) times more at risk for elevated liver enzymes . No other correlations between AEs and EFV pharmacokinetics or patient characteristics could be identified . CONCLUSIONS Pharmacokinetic parameters of NVP did not have a relationship to AEs in the 2NN trial when corrected for known covariates . The value of periodical drug monitoring of NVP as a way to prevent toxicity is therefore limited . Treating physicians should instead focus on factors that are more predictive of AEs ( gender , CD4 count and hepatitis coinfection ) . High EFV Cmin levels result ed in elevated liver enzyme values during the first 6 weeks of treatment . Regular measurement of EFV levels and liver enzymes at the start of therapy may therefore be advised CONTEXT Rifampicin-based antitubercular therapy reduces the plasma concentrations of nevirapine and efavirenz . The virological consequences of these interactions are not well described . OBJECTIVE To assess the effectiveness and tolerability of concomitant efavirenz- or nevirapine-based combination antiretroviral therapy and rifampicin-based antitubercular therapy . DESIGN , SETTING , AND PARTICIPANTS Cohort analysis of prospect ively collected routine clinical data in a community-based South African antiretroviral treatment program . Antiretroviral treatment-naive adults enrolled between May 2001 and June 2006 were included in the analysis , and were followed up until the end of 2006 . INTERVENTIONS Patients starting antiretroviral therapy with or without concurrent antitubercular therapy received either efavirenz or nevirapine at st and ard doses . Patients developing tuberculosis while taking antiretroviral therapy that included nevirapine were either changed to efavirenz or continued taking nevirapine . MAIN OUTCOME MEASURES Viral load of 400 copies/mL or more after 6 , 12 , and 18 months of antiretroviral therapy ; time to the first viral load of 400 copies/mL or more ; time to confirmed virological failure ( 2 consecutive values > or = 5000 copies/mL ) ; time to death ; and time to treatment-limiting toxicity were assessed . RESULTS The analysis included 2035 individuals who started antiretroviral therapy with efavirenz ( 1074 with concurrent tuberculosis ) and 1935 with nevirapine ( 209 with concurrent tuberculosis ) . There were no differences in time to death or substitution of either antiretroviral drug for toxicity with and without concurrent tuberculosis . Patients starting nevirapine with concurrent tuberculosis were at a higher risk of elevated viral load most notably at 6 months ( 16.3 % ; 95 % confidence interval [ CI ] , 10.6%-23.5 % ) than those without tuberculosis ( 8.3 % ; 95 % CI , 6.7%-10.0 % ; adjusted odds ratio [ OR ] , 2.1 ; 95 % CI , 1.2 - 3.4 ; and in the combined estimate , adjusted OR , 1.7 ; 95 % CI , 1.2 - 2.6 ) . In the time-to-event analysis of confirmed virological failure ( 2 consecutive values of > or = 5000 copies/mL ) , patients starting nevirapine with concurrent tuberculosis developed virological failure sooner ( adjusted hazard ratio [ HR ] 2.2 ; 95 % CI , 1.3 - 3.7 ) . There were no differences between patients starting efavirenz with and without concurrent tuberculosis ( adjusted OR , 1.1 ; 95 % CI , 0.8 - 1.5 [ combined estimate ] and adjusted HR , 1.1 ; 95 % CI , 0.6 - 2.0 , respectively ) . There was no difference in time to virological rebound in patients free of tuberculosis and those developing tuberculosis during follow-up while taking nevirapine ( adjusted HR , 1.0 ; 95 % CI , 0.5 - 2.0 ) or efavirenz ( adjusted HR , 0.8 ; 95 % CI , 0.4 - 1.7 ) . CONCLUSION In this cohort study , virological outcomes were inferior when nevirapine-based antiretroviral therapy was commenced while taking antitubercular treatment ( vs without concurrent tuberculosis ) but comparable when starting efavirenz-based antiretroviral therapy ( vs without concurrent tuberculosis ) or when tuberculosis developed while taking established nevirapine- or efavirenz-based therapies Abstract PURPOSE : A r and omized , open-label , pilot study was undertaken to explore the antiviral activity and tolerability of two nonnucleoside reverse transcriptase inhibitors ( NNRTIs ) , nevirapine ( NVP ) and efavirenz ( EFV ) . METHOD : HIV-infected antiretroviral-naive adults with CD4 counts > 100 cells/mm3 and detectable plasma HIV RNA below 100,000 copies/mL were r and omized to receive didanosine ( ddI ) and stavudine ( d4 T ) plus either NVP or EFV . Assessment s were made every 12 weeks . Primary endpoints were the proportion of patients reaching plasma HIV RNA < 50 copies/mL and /or developing NNRTI-related toxicities leading to drug discontinuation . Baseline characteristics were comparable for participants in the EFV ( n = 31 ) and NVP arms ( n = 36 ) . RESULTS : At 48 weeks , 23/31 ( 74 % ) patients in the EFV group and 23/36 ( 64 % ) in the NVP group had < 50 HIV RNA copies/mL ( intention-to-treat analysis ) . Adverse events led to NNRTI discontinuation in 4 and 3 patients in the EFV and NVP arms , respectively . There were no statistically significant differences between groups regarding any primary endpoint . NVP and EFV along with two NRTIs may be equally well tolerated and effective at achieving < 50 HIV RNA copies/mL in naive patients with CD4 counts > 100 cells/mm3 and HIV RNA < 105 copies/mL. CONCLUSION : A much larger study is needed to demonstrate any significant differences between NVP and EFV , if they exist at all OBJECTIVE To study and compare the pattern of lipid profile changes in Thai HIV and tuberculosis ( TB ) co-infected patients after receiving two non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy ( ART ) . MATERIAL AND METHOD From an open label , r and omized , comparative trial comparing treatment outcome between HIV and TB co-infected patients receiving nevirapine ( NVP ) or efavirenz ( EFV ) combined with stavudine and lamivudine , patient 's body mass index ( BMI ) , CD4 cell count , plasma HIV-1 RNA , fasting blood glucose , plasma total cholesterol ( TC ) , low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , and triglyceride ( TG ) were collected at baseline , 24 , and 48 weeks of ART . RESULTS Of the 121 patients included in the present study , mean ( SD ) age was 36.9 ( 8.4 ) years and 66 % were male . After 48 weeks of ART the median ( IQR ) percentage of TC , LDL-C , HDL-C and TG values were 21.1 % ( 5.4 - 40.7 ) , 23.5 % ( -0.8 - 49.8 ) , 22.7 % ( 0 - 50 ) and -1.0 % ( -34.6 - 32.2 ) respectively . The median ( IQR ) percentage change of the HDL-C value was significantly higher in NVP-based than EFV-based ART ( 31.9 [ 9.6 - 50.0 ] vs. 12.2 [ -8.8 - 51.2 ] ; p = 0.03 ) . The proportions of patients with high TC ( 21.5 % ) and high LDL-C ( 29.2 % ) increased and low HDL-C ( 11.6 % ) decreased significantly at 48 weeks of ART compared to baseline ( all , p < 0.01 ) . The proportions of patients with high TC , high TG and low HDL-C were significantly higher in the EFV group than in the NVP group ( p = 0.03 for high TC , p = .01 for high TG and p < 0.01 for low HDL-C ) . CONCLUSION NNRTI-based ART is associated with increases of TC , LDL-C and HDL-C values in Thai HIV and TB co-infected patients . More favorable lipid profile is observed in NVP-based than EFV-based ART OBJECTIVE Our objective was to compare immunologic effectiveness of nevirapine and efavirenz based antiretroviral therapy in antiretroviral naïve HIV-1 infected Indian patients . DESIGN AND METHODS Study was an observational , non-r and omized , longitudinal cohort . Antiretroviral naive HIV-1 infected patients receiving efavirenz + 2NRTI ( n=254 ) and nevirapine + 2 NRTI ( n=857 ) from April 2000 were followed up at two tertiary care HIV clinics at Ahmedabad and Pune . Patients were followed up clinical ly monthly and CD4 was carried out every 3 monthly . All patients were examined for various side effects as well as development of various OIs . Data were analyzed using st and ard statistical methods . RESULTS Baseline characteristics for both the groups ( NVP and EFV ) were comparable . In the r and om effects model , there was an increase of 40.97 ( p < 0.05 ) units of CD4 cell counts with an unit increase in time in the NVP arm as against a 44.75 ( p < 0.05 ) units of increase in CD4 cell counts in the EFV group with a unit increase in time , which is significant for both groups . However , at any given point of time there was no difference in the rate of increase of CD4 count between the two treatment arms ( p = 0.58 ) . Hypersensitivity reaction ( 6.6 % in NVP vs. 2.32 % in EFV , p = 0.0146 ) and hepatitis ( 3.2 % in NVP vs. 0 % in EFV , p = 0.0085 ) were more common with nevirapine , while neurologic disturbances ( 0.93 % in NVP vs. 20.15 % in EFV , p = 0.0001 ) were more common with efavirenz . Incidence of distal sensory neuropathy and lipid abnormalities was similar in both the groups . CONCLUSION Use of NVP and EFV based HAART in antiretroviral naive Indian patients led to significant and durable rise in CD4 cell count . Although observational and non-r and omized , our study showed equivalent immunological response amongst NVP and EFV based HAART which is in line with the results of the 2NN study Background Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis ( HIV-TB patients ) . Nevirapine is a much cheaper drug than its alternative efavirenz , and might be beneficial in re source constrained setting s. Methods A r and omised open label trial was conducted at All India Institute of Medical Sciences , New Delhi , India . During the regimen of an antiretroviral therapy ( ART ) , naive HIV-TB patients were r and omly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy ( ATT ) . Participants were followed for 24 months after starting ART . The end points were virological , immunological and clinical responses , and progression of HIV disease marked by failure of ART . Results Of the 135 HIV-TB patients , who were receiving rifampicin based ATT , 68 were selected r and omly to receive efavirenz based ART and 67 to receive nevirapine based ART . The virological failure rates in the overall population , and the nevirapine and efavirenz groups were 14.1 % ( 19/135 ) ; 14.9 % ( 10/67 ) and 13.2 % ( 9/68 ) , respectively ( p = 0.94 ) . No significant difference was found between the groups in the rate of clinical , immunological or virological failures . The overall mortality was 17 % with no significant difference between the two groups . Except for the lead in period on day 14 , the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group . Conclusions Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference , irrespective of whether efavirenz or nevirapine was used . Therefore , nevirapine based ART could be an alternative in the re source limited setting s in patients with HIV and tuberculosis co-infection . Trial registration NCT No. 01805258 OBJECTIVE The aim of this 2NN pharmacokinetic sub study was to investigate the population pharmacokinetics of nevirapine and efavirenz . METHODS Treatment-naive , HIV-1-infected patients received nevirapine ( once or twice daily ) , efavirenz or a combination with lamivudine and stavudine . Blood sample s were collected on day 3 and weeks 1 , 2 , 4 , 24 and 48 . Using non-linear mixed effects modelling , pharmacokinetics of nevirapine and efavirenz and factors involved in the inter-individual variability were investigated . RESULTS Clearance of nevirapine in the induction phase ( < 14 days ) and at steady state ( > 28 days ) were 2.02 I/h and 2.81 I/h , respectively . Volume of distribution and absorption rate constant were 77.0 l and 1.66 h(-1 ) , respectively . Clearance of nevirapine was lower in females ( 13.8 % ) and in patients with hepatitis B ( 19.5 % ) . Patients from South America and Western countries had higher clearance of nevirapine compared with Thai and South African patients . The clearances of efavirenz in the induction phase and at steady state were 7.95 l/h and 8.82 l/h , respectively . The volume of distribution and absorption rate constant were 4181 and 0.287 h(-1 ) , respectively . Concomitant use of nevirapine increased clearance of efavirenz ( 43 % ) . Patients from Thail and had lower clearance than the rest of the population . CONCLUSIONS The population pharmacokinetics of nevirapine and efavirenz were assessed in the 2NN trial . For both drugs , an induction phase was distinguished from the steady-state phase . Gender , hepatitis B and geographical region were involved in the variability of the pharmacokinetics of nevirapine . Region and concomitantly used nevirapine were determinants of the pharmacokinetics of efavirenz OBJECTIVE To assess whether differences in safety profiles between nevirapine ( NVP ) and efavirenz ( EFV ) , as observed in the 2NN study , translated into differences in ' health related quality of life ' ( HRQoL ) . DESIGN A sub- study of the 2NN study , with antiretroviral-naive patients r and omly allocated to NVP ( once or twice daily ) , EFV or NVP+EFV , in addition to stavudine and lamivudine . METHODS Comparing differences in changes of HRQoL over 48 weeks as measured with the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) question naire , using analysis of variance . RESULTS The 2NN study enrolled 1216 patients . No vali date d question naires were available for 244 patients , and 55 patients had no HRQoL data at all , leaving 917 patients eligible for this sub- study . A total of 471 ( 51 % ) had HRQoL measurements both at baseline and week 48 . The majority ( 69 % ) of patients without HRQoL measurements did , however , complete the study . The change in the physical health score ( PHS ) was 3.9 for NVP , 3.4 for EFV and 2.4 for NVP+EFV ( P=0.712 ) . For the mental health score ( MHS ) these values were 6.1 , 7.0 and 3.9 , respectively ( P=0.098 ) . A baseline plasma HIV-1 RNA concentration ( pVL ) > or = 100,000 copies/ml and a decline in pVL ( per log10 ) were independently associated with an increase of PHS . An increase of MHS was only associated with pVL decline . Patients experiencing an adverse event during follow-up had a comparable change in PHS but a significantly smaller change in MHS , compared with those without an adverse event . CONCLUSIONS First-line ART containing NVP and /or EFV leads to an improvement in HRQoL. The gain in HRQoL was similar for NVP and EFV , but slightly lower for the combination of these drugs Background : National initiatives offering non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy ( cART ) have exp and ed in sub-Saharan Africa . The Tshepo study is the first clinical trial evaluating the long-term efficacy and tolerability of efavirenz versus nevirapine-based cART among adults in Botswana . Methods : A 3-year r and omized study ( n = 650 ) using a 3 × 2 × 2 factorial design comparing efficacy and tolerability among : ( i ) zidovudine/lamivudine versus zidovudine/didanosine versus stavudine/lamivudine ; ( ii ) efavirenz versus nevirapine ; and ( iii ) community-based supervision versus st and ard adherence strategies . This paper focuses on comparison ( ii ) . Results : There was no significant difference by assigned NNRTI in time to virological failure with resistance ( log-rank P = 0.14 ) , nevirapine versus efavirenz [ risk ratio ( RR ) 1.54 , 95 % CI 0.86–2.70 ] . Rates of virological failure with resistance were 9.6 % nevirapine-treated ( 95 % CI 6.8–13.5 ) versus 6.6 % efavirenz-treated ( 95 % CI 4.2–10.0 ) at 3 years . Women receiving nevirapine-based cART trended towards higher virological failure rates when compared with efavirenz-treated women , Holm-corrected ( log-rank P = 0.072 ) , nevirapine versus efavirenz ( RR 2.22 , 95 % CI 0.94–5.00 ) . A total of 139 patients had 176 treatment-modifying toxicities , with a shorter time to event in nevirapine-treated versus efavirenz-treated patients ( RR 1.85 , 1.20–2.86 ; log-rank P = 0.0002 ) . Conclusion : Tshepo-treated patients had excellent overall immunological and virological outcomes , and no significant differences were observed by r and omized NNRTI comparison . Nevirapine-treated women trended towards higher virological failure with resistance compared with efavirenz-treated women . Nevirapine-treated adults had higher treatment modifying toxicity rates when compared with those receiving efavirenz . Nevirapine-based cART can continue to be offered to women in sub-Saharan Africa if patient education concerning toxicity is emphasized , routine safety monitoring chemistries are performed and the potential risk of efavirenz-related teratogenicity is considered BACKGROUND In countries with a high incidence of HIV and tuberculosis co-infection , nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs . We aim ed to compare efficacy and safety of a nevirapine-based antiretroviral therapy ( started at full dose ) with an efavirenz-based regimen in co-infected patients . METHODS We did a multicentre , open-label , r and omised , non-inferiority trial at three health centres in Maputo , Mozambique . We enrolled adults ( ≥18 years ) with tuberculosis and previously untreated HIV infection ( CD4 cell counts < 250 cells per μL ) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal . 4 - 6 weeks after the start of tuberculosis treatment , we r and omly allocated patients ( 1:1 ) with central r and omisation , block sizes of two to six , and stratified by site and CD4 cell count to nevirapine ( 200 mg twice daily ) or efavirenz ( 600 mg once daily ) , plus lamivudine and stavudine . The primary endpoint was virological suppression at 48 weeks ( HIV-1 RNA < 50 copies per mL ) in all patients who received at least one dose of study drug ( intention-to-treat population ) ; death and loss to follow-up were recorded as treatment failure . The non-inferiority margin for the difference of efficacy was 10 % . We assessed efficacy in intention-to-treat and per- protocol population s and safety in all patients who received study drug . This study is registered with Clinical Trials.gov , number NCT00495326 . FINDINGS Between October , 2007 , and March , 2010 , we enrolled 285 patients into each group . 242 ( 85 % ) patients in the nevirapine group and 233 ( 82 % ) patients in the efavirenz group completed follow-up . In the intention-to-treat population , 184 patients ( 64·6 % , 95 % CI 58·7 - 70·1 ) allocated nevirapine achieved virological suppression at week 48 , as did 199 patients ( 69·8 % , 64·1 - 75·1 ) allocated efavirenz ( one-sided 95 % CI of the difference of efficacy 11·7 % ) . In the per- protocol population , 170 ( 70·0 % , 63·8 - 75·7 ) of 243 patients allocated nevirapine achieved virological suppression at week 48 , as did 194 ( 78·9 % , 73·2 - 83·8 ) of 246 patients allocated efavirenz ( one-sided 95 % CI 15·4 % ) . The median CD4 cell count at r and omisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine . 20 patients allocated nevirapine ( 7 % ) had grade 3 - 4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz ( 6 % ) . Three patients had severe rash after receipt of nevirapine ( 1 % ) but no patients did after receipt of efavirenz . 18 patients in the nevirapine group died , as did 17 patients in the efavirenz group . INTERPRETATION Although non-inferiority of the nevirapine-regimen was not shown , nevirapine at full dose could be a safe , acceptable alternative for patients unable to tolerate efavirenz . FUNDING French Research Agency for HIV/AIDS and hepatitis ( ANRS ) Background Guidelines recommend both protease inhibitor (PI)- and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens for initial therapy in HIV-positive individuals whilst clinical trial data comparing treatment options remain limited . Objective To assess whether drug selection ( PI versus NNRTI ) in antiretroviral-naive patients is related to virological response at 6 months within a clinical cohort . Design Data bases from two large clinics were used to identify all treatment-naive patients initiating highly active antiretroviral therapy ( PI/ two PI or NNRTI ) . Statistical models determined the likelihood of suppressing HIV viral load < 500 copies/ml , the risk of treatment failure by 6 months , and factors associated with treatment success . Results Of 1109 potentially eligible patients 888 met study criteria and were included ; 484 were prescribed a PI ( 40 % indinavir , 41 % nelfinavir ) and 404 were prescribed NNRTI ( 40 % efavirenz , 60 % nevirapine ) . Three treatment arms were compared : efavirenz versus nevirapine versus PI . After stratification by year and centre and adjustment for baseline variables , only treatment group and baseline viral load remained significantly associated with virological suppression at 6 months . Patients on efavirenz were significantly more likely to achieve an undetectable viral load than those on PI or nevirapine . The relative hazard for nevirapine was 0.77 ( 95 % confidence interval , 0.61–0.96 , P = 0.02 ) and that for PI was 0.74 ( 95 % confidence interval , 0.58–0.94 , P = 0.01 ) . Efavirenz also performed better in the analysis of treatment failure at 6 months . Conclusion Although observational cohort data may be susceptible to significant bias , this study suggests a better initial virological response for efavirenz compared to either nevirapine or the PI . Clinical trial data is required to confirm these findings To evaluate the rate of and risk factors for hepatotoxicity in tuberculosis ( TB ) and human immunodeficiency virus type 1 ( HIV-1 ) co-infected patients while receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy ( ART ) and a rifampicin (RMP)-containing anti-TB regimen . We analyzed data from the N2R study which was an open label , r and omized , comparative trial comparing treatment outcomes between 71 TB/HIV-1 co-infected patients receiving efavirenz (EFV)-based and nevirapine (NVP)-based ART ; all of whom were receiving RMP-containing anti-TB treatment . Demographic data , liver function test , CD4 cell count , plasma HIV-1 RNA , hepatitis B surface antigen and anti-hepatitis C virus antibody were collected before initiating ART ( week 0 ) . Liver enzymes and total bilirubin levels were monitored at 6 weeks , 12 weeks and 24 weeks after ART initiation . All patients were followed until TB therapy was completed . Of 142 patients , 8 patients were excluded . Among the remaining 134 patients , the mean+/-SD age was 36.8+/-8.6 years and 67.2 % were male . Severe hepatotoxicity ( grade 3 or 4 ) developed in 4 patients ( 2.9 % ) ; 3 patients ( 4.6 % ) in the NVP group and 1 patient ( 1.4 % ) in the EFV group . Severe hyperbilirubinemia ( grade 3 or 4 ) occurred in 7 patients ( 5.2 % ) ; 5 patients ( 7.7 % ) in the NVP group and 2 patients ( 2.9 % ) in the EFV group . Grade 1 or 2 hepatotoxicity occurred in 34 patients ( 31.4 % ) . Hepatitis C virus co-infection ( adjusted OR 3.03 ; 95%CI 1.26 - 7.29 ) was an independent risk factor associated with grade 1 - 4 hepatotoxicity ( p=0.013 ) . Monitoring of hepatotoxicity should be considered in TB/HIV-1 co-infected patients who are infected with HCV and receiving NVP Objective : To determine the incidence and risk factors for rash in Thai patients taking four different non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens . Methods : HIV-positive , antiretroviral-naive patients enrolled in the 2NN study in Thail and and followed for at least 1 week were included . Patients were r and omized to efavirenz ( EFV ) 600 mg once daily ( OD ) versus nevirapine ( NVP ) 200 mg twice daily ( BD ) versus NVP 400 mg OD versus NVP 400 mg OD + EFV 800 mg OD with stavudine/lamivudine . Results : Of 202 patients , 95 ( 47 % ) and 69 ( 34.2 % ) developed a rash from all reasons and from NNRTI , respectively . For NNRTI-related rash the incidences were EFV ( 20 % ) , NVP BD ( 21 % ) , NVP OD ( 38 % ) and NVP + EFV ( 67 % ) . The proportions of patients with grade I , II and III within the four treatment arms are as follows : EFV , 4.3 , 13 and 2.9 % ; NVP BD , 2.3 , 15.9 and 2.3 % ; NVP OD , 12.8 , 19.1 and 6.4 % ; and NVP + EFV , 11.9 , 47.6 and 7.1 % . Multivariate analyses showed females with CD4 cell count ≥250 × 106 cells/l , high body mass index ( > 21.3 kg/m2 ) , and a rise in CD4 ( ≥53 × 106 cells/l ) and alanine aminotransferase ( ALT ) ( ≥34 U/l ) at week 4 to be risk factors for rash . Conclusions : Thai patients had a high incidence of NNRTI-related rash when treated with NVP + EFV or NVP OD . NVP if used BD had the same rash incidence as EFV for rash of all grade s. Females , and persons with earlier HIV disease or with a large rise in CD4 + cell count after starting therapy are at greater risk for NNRTI-related The CPCRA ( Terry Beirn Community Programs for Clinical Research on AIDS ) 058 FIRST ( Flexible Initial Retrovirus Suppressive Therapies ) trial is a large , long-term , r and omized , prospect i ve comparison of three different antiretroviral strategies in highly active antiretroviral therapy-naïve , HIV-1-infected persons . The trial was design ed as a flexible framework upon which other studies could be added to answer more limited , but still important , questions . This article presents the study design , discusses the challenges we have faced in implementing the trial , and describes our preliminary experiences . Control Clin Trials 2001;22:176 - Objective : To describe early hospitalization for severe malnutrition in HIV-infected children initiating antiretroviral therapy ( ART ) . Design : R and omized trial of induction-maintenance and monitoring strategies in HIV-infected children . Setting : Three tertiary hospitals in Ug and a and one in Zimbabwe . Participants : 1207 HIV-infected children , median age 6 years ( range , 3 months to 17 years ) . Intervention : Abacavir , lamivudine and nevirapine or efavirenz were given ; children in induction-maintenance arms also received zidovudine to week 36 . Pre-ART inpatient/outpatient nutritional rehabilitation for children with baseline severe malnutrition . Main outcome measures : Hospitalization for severe malnutrition and change in CD4 cell percentage by week 12 after ART . Mortality and change in weight-for-age Z-score ( WAZ ) by week 24 after ART . Results : Thirty-nine of 1207 ( 3.2 % ) children were hospitalized for severe malnutrition ( 20 with oedema ) , median 28 days [ interquartile range ( IQR ) 14 , 36 ] after ART for marasmus and 26 days ( IQR 14 , 56 ) after ART for kwashiorkor . Hospitalized children had lower baseline and greater 24-week rise in WAZ than nonhospitalized children ( P < 0.001 ) . Twenty-nine of 39 ( 74 % ) children admitted for severe malnutrition had underlying infections . Of 220 children with advanced disease ( baseline WAZ and CD4 cell Z-scores both < −3 ) , 7.3 % [ 95 % confidence interval ( CI ) 3.8 , 10.7 ] developed kwashiorkor and 3.6 % ( 95 % CI 1.2 , 6.1 ) developed marasmus by week 12 . CD4 cell percentage rise was similar among groups ( P = 0.37 ) . Twenty-four-week mortality was 32 , 20 and 1.7 % among children hospitalized with marasmus , kwashiorkor and not hospitalized , respectively , ( P < 0.001 ) . Conclusion : One in nine children with advanced HIV required early hospitalization for severe malnutrition after ART , with a 15-fold increase in 6-month mortality compared with nonhospitalized children . Integration of HIV/malnutrition services and further research to determine optimal ART timing , role of supplementary feeding and antimicrobial prophylaxis are urgently required Backgound : A substantial number of patients start their first-line antiretroviral therapy at an advanced stage of an HIV-1 infection . Potential differences between specific drug regimens in antiviral efficacy and safety in these patients are of major importance . Methods : A post-hoc analysis within the r and omized controlled 2NN trial comparing efficacy between regimes containing nevirapine ( NVP ) , efavirenz ( EFV ) , or both , in addition to stavudine and lamivudine . Primary outcome : risk of virologic failure in different strata of baseline CD4 T-lymphocyte counts and plasma HIV-1 RNA concentrations ( pVL ) . Virologic failure : never reaching a pVL < 400 copies/ml , or a rebound to two consecutive values > 400 copies/ml . Results : The risk of virologic failure was increased at very low CD4 counts ( < 25 × 106 cells/l ) compared to CD4 counts > 200 × 106 cells/l [ hazard ratio ( HR ) , 1.28 ; 95 % confidence interval ( CI ) , 0.93–1.77 ] . The same was seen for a pVL ≥ 100 000 copies/ml compared to a lower pVL ( HR , 1.20 ; CI , 0.96–1.50 ) . There were no statistically significant differences between NVP and EFV in risk of virologic failure within any of the CD4 or pVL strata , although EFV performed slightly better in the low CD4 stratum . The incidence of rash in the NVP group was significantly higher in female patients with higher CD4 cell counts , while adverse events in the EFV group were not associated with CD4 cell count . Conclusions : Initial antiretroviral therapy including NVP or EFV is effective in patients with an advanced HIV-1 infection . A high baseline CD4 cell count is associated with the occurrence of rash in female patients using NVP BACKGROUND The aim of the present study was to determine appropriate tenofovir-based regimens meriting evaluation in large-scale r and omized trials among sub-Saharan African patients . METHODS This was a r and omized open-label 96-week prospect i ve pilot study evaluating four first-line regimens : tenofovir/emtricitabine/nevirapine ( group 1 ) , tenofovir/lopinavir/ritonavir ( group 2 ) , tenofovir/emtricitabine/zidovudine ( group 3 ) and tenofovir/emtricitabine/efavirenz ( group 4 ) in antiretroviral-naive , HIV-1-infected patients in Senegal and Cameroon . The primary end point was defined as an HIV-1 RNA viral load < 50 copies/ml ( study detection limit ) at week 16 in ≥50 % of patients using intention-to-treat analysis . RESULTS At baseline , 119 patients included were 34 % male , had a median plasma viral load of 5.4 log10 copies/ml and median CD4(+ ) T-cell count of 200 cells/mm(3 ) ( range 53 - 358 ) . The primary end point was achieved for groups 1 , 3 and 4 ( 58 % [ n=31 ] , 62 % [ n=29 ] and 53 % [ n=30 ] , respectively ) , but not for group 2 ( 38 % [ n=29 ] ) . At week 96 , undetectable HIV-1 RNA had been achieved in 74 % of patients in group 1 , 38 % in group 2 , 72 % in group 3 and 73 % in group 4 . Patients with detectable HIV-1 RNA at week 16 were more likely to have baseline HIV-1 RNA≥100,000 copies/ml ( adjusted OR 5.56 , 95 % CI 1.72 , 16.67 ) . HIV mutations associated with protease inhibitor resistance emerged in three patients , all of whom were in group 2 . Anaemia occurred in two group 3 patients and was the only serious treatment-related adverse event . CONCLUSIONS Three efficient and safe tenofovir-based triple regimens were identified ; the two-drug regimen ( tenofovir/lopinavir/ritonavir ) did not achieve the protocol -defined virological threshold of efficacy BACKGROUND We analyzed the effect of exposure to nonnucleoside reverse-transcriptase inhibitors ( NNRTIs ) and protease inhibitors ( PIs ) on the progression of liver fibrosis in patients with human immunodeficiency virus ( HIV ) and hepatitis C virus coinfection . METHODS We analyzed data and liver biopsy findings for 201 coinfected patients . Fibrosis was scored following the French METAVIR Cooperative Study Group . We used multinomial logistic regression analysis and the fibrosis progression rate to assess the association between cumulative exposure to antiretroviral drugs and stage of fibrosis . RESULTS The adjusted odds ratio ( AOR ) and 95 % confidence interval ( CI ) of having a fibrosis stage score of 0 or 1 , compared with 3 or 4 , increased with each additional year of exposure to HAART ( AOR , 1.32 ; 95 % CI , 1.04 - 1,67 ) , to NNRTIs as a class ( AOR , 1.64 ; 95 % CI , 1.18 - 2.27 ) , to efavirenz ( AOR , 1.54 ; 95 % CI , 1.03 - 2.30 ) , and to nevirapine ( AOR , 1.72 ; 95 % CI , 1.15 - 2.78 ) . This effect was not found with PIs as a class . The AOR ( 95 % CI ) of having a fibrosis stage score of 2 versus 3 or 4 increased with each additional year of exposure to NNRTIs ( AOR , 1.51 ; 95 % CI , 1.08 - 2.10 ) and nevirapine ( AOR , 1.58 ; 95 % CI , 1.06 - 2.37 ) . This effect was not found with highly active antiretroviral therapy , PIs , or efavirenz . The AOR ( 95 % CI ) of having a fibrosis progression rate < or = 0.1 versus > 0.1 increased with each additional year of exposure to highly active antiretroviral therapy ( AOR , 1.31 ; 95 % CI , 1.07 - 1.60 ) , to NNRTIs ( AOR , 1.33 ; 95 % CI , 1.03 - 1.70 ) , and to nevirapine ( AOR , 1.44 ; 95 % CI , 1.07 - 1.95 ) . This effect was not found with PIs or with efavirenz . CONCLUSIONS In contrast with previous studies , we found that exposure to NNRTIs was clearly associated with a reduction in fibrosis progression , whereas exposure to PIs was not . Of note , exposure to nevirapine was more consistently associated with a reduction in fibrosis progression than was exposure to efavirenz . Prospect i ve work is needed in this area The non-nucleoside reverse transcriptase inhibitors ( NNRTIs ) efavirenz ( EFV ) and nevirapine ( NVP ) taken in combination with nucleoside reverse transcriptase inhibitors ( NRTIs ) have both shown to be just as highly effective as protease inhibitors ( PIs ) in reducing viral load in patients infected with HIV . Our study compares the performance of these two NNRTIs with each other . This was a non-r and omized , prospect i ve , two-arm , multi-centre trial . We evaluated all patients with an EFV- or NVP-containing antiretroviral regimen . The primary endpoint was the difference in success rates defined as a viral load of < /=50 copies/mL at week 48 . chi(2)-tests were used for naïve and pretreated patients using intention-to-treat ( ITT ) and on-treatment analysis . As secondary endpoints , a viral load of < /=500 copies/mL and CD4 count at week 48 for naïve patients were evaluated . A Cox regression was used to adjust for prespecified covariates . We included 662 patients ( NVP 337 , EFV 325 ) . The difference in success rates in the ITT analysis was 4.5 % ( -11.5 % , 19.0 % ) , P=0.578 . Pretreated patients with a triple therapy show a difference of 10.1 ( -0.3 , 20.6 ) , P=0.056 . Non-significant results appeared for all secondary analyses . In this trial , no difference between EFV and NVP in combination with NRTI backbone therapy can be shown , regarding viral load . Further r and omized studies are necessary to evaluate possible differences BACKGROUND Coinfection with hepatitis C virus ( HCV ) and human immunodeficiency virus ( HIV ) is a known risk factor for hepatotoxicity in patients receiving highly active antiretroviral therapy ( HAART ) . The aim of this study was to evaluate the role of HCV-related liver fibrosis in HAART-associated hepatotoxicity . METHODS In a prospect i ve study involving 107 patients who underwent liver biopsy , fibrosis was grade d according 5 stages , from F0 ( no fibrosis ) to F4 ( cirrhosis ) . Hepatotoxicity was defined as an increase in levels of aspartate aminotransferase and alanine aminotransferase to > 5 times the upper limit of normal , or a > 3.5-fold increase if baseline levels were abnormal . The incidence of hepatotoxicity was compared with liver fibrosis stage and with time and composition of HAART . RESULTS Overall , 27 patients ( 25 % ) had hepatotoxic events ( 5.1 events/100 person-years of therapy ) . The incidence was greater for patients with stage F3 or F4 fibrosis ( 38 % ) than for those with stage F1 or F2 fibrosis ( 15 % ; 7.6 vs. 3 events/100 person-years ; relative risk , 2.75 ; 95 % confidence interval , 1.08 - 6.97 ; P=.013 ) . Duration of HCV infection , duration of HAART , diagnosis of acquired immunodeficiency syndrome , HCV load , HCV genotype , and nadir CD4(+ ) cell count did not affect the risk of hepatotoxicity . Of the 86 patients who received nonnucleoside reverse-transcriptase inhibitors ( NNRTIs ) , 11 ( 13 % ) developed liver toxicity . In these patients , fibrosis stages F1 and F2 were associated with similar rates of toxicity ( 3 events/100 person-years for patients who received nevirapine , 3.3 events/100 person-years for those who received efavirenz , and 3.4 events/100 person-years for those who received non-NNRTIs ) . There was a greater incidence among patients with F3 or F4 fibrosis who received NNRTIs ( 11.7 events/100 person-years for patients who received nevirapine , and 8.6 events/100 person-years for those who received efavirenz ) , compared with those who received non-NNRTIs ( 4 events/100 person-years ) . CONCLUSIONS HAART-associated hepatotoxicity correlates with liver histological stage in patients coinfected with HIV and HCV . There was no difference in hepatotoxicity risk for different antiretroviral therapies in patients with mild-to-moderate fibrosis BACKGROUND Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy ( HAART ) has been the most affordable regimen for the HIV-infected in developing countries . There are limited data comparing nevirapine ( NVP ) to efavirenz ( EFV ) in HIV-infected children . This study aim ed to assess the efficacy and tolerability of NVP-based regimens compared to EFV-based regimens in HIV-infected children in Thail and . METHODS The medical records of HIV-infected children who had received NNRTI-based regimens for more than 6 months at the Department of Pediatrics , Siriraj Hospital , Mahidol University , Thail and , were review ed . RESULTS Of the 139 HIV-infected children studied , 70 were male , and the median age at treatment initiation was 6.08 years ( range 0.32 - 14.56 years ) ; the median duration of follow-up was 36 months ( range 6 - 66 months ) . The median baseline CD4 cell count was 185cells/mm(3 ) ( range 2 - 3482cells/mm(3 ) ) and the median baseline CD4 percentage was 7.20 % ( range 0.11 - 36.57 % ) . An NVP-based regimen was initiated in 61 ( 44 % ) : 38 antiretroviral (ARV)-naïve and 23 ARV-experienced . An EFV-based regimen was initiated in 78 ( 56 % ) : 34 ARV-naïve and 44 ARV-experienced . The CD4 cell count and percentage gains were not different between the NVP and EFV groups in both the ARV-naïve and the ARV-experienced . However , ARV-naïve children who received an EFV regimen had significantly lower baseline CD4 levels than those who received an NVP regimen . ARV-naïve children had a better CD4 response than the ARV-experienced . The survival rates of children in the NVP groups were not different from those in the EFV groups for both the ARV-naïve and the ARV-experienced . Treatment failure occurred in one ARV-naïve NVP case ( 2.6 % ) , two ARV-naïve EFV cases ( 5.8 % ) , and nine ARV-experienced NVP cases ( 39 % ) at 24 months of treatment , and 11 ARV-experienced EFV cases ( 25 % ) at 18 months of treatment . Seven ( 10 % ) children had adverse effects from treatment with NVP . The main side effects were rash and hepatitis ; six had to switch to EFV . Four ( 5 % ) children had adverse effects from treatment with EFV ; two had to switch to NVP . CONCLUSIONS Both NVP- and EFV-based HAART regimens were effective in children in Thail and for at least 3 years . HIV-infected Thai children generally tolerated NNRTI well OBJECTIVE To compare virological and immunological responses to nevirapine (NVP)-based and efavirenz (EFV)-based highly active antiretroviral therapy ( HAART ) regimens in antiretroviral-naïve patients with advanced HIV infection . METHODS A retrospective observational cohort study was conducted on antiretroviral-naïve HIV-infected patients whose pretreatment CD4 cell counts were less than 100 cells/microL or whose viral loads were greater than 100,000 HIV-1 RNA copies/mL. RESULTS Baseline characteristics of patients in the NVP ( n=24 ) and EFV ( n=29 ) groups were not different . The proportion of patients with viral loads > 100,000 copies/mL was higher in the EFV group . The probability of virological success estimated by the Kaplan-Meier method showed that 3- and 6-month success rates were 30.8 % [ 95 % confidence interval ( CI ) : 16.7 - 52.2 % ] and 63.1 % ( 95 % CI : 44.7 - 81.3 % ) for the NVP group . The corresponding values were 41.2 % ( 95 % CI : 25.8 - 61.0 % ) and 62.9 % ( 95 % CI : 45.7 - 80.1 % ) for the EFV-based group . The median success times of the two groups were about 4 and 3 months ( P=0.678 ) , respectively , for NVP and EFV . Cox 's proportional hazard was used after adjusting for age , previous opportunistic infections ( OIs ) , and viral load at baseline , and showed that patients who received the NVP-based regimen had about 25 % [ hazard ratio (HR)=0.75 , 95 % CI : 0.37 - 1.51 ] less chance of virological success than patients who received the EFV-based regimen ( P=0.415 ) . The median times to CD4 > or = 100 cells/microL were 5.6 and 4.4 months for the NVP- and EFV-based regimens , respectively ( log-rank test , P=0.144 ) . CONCLUSIONS NVP- and EFV-based HAART regimens as initial regimens in patients with advanced HIV infection are effective and comparable , in term of virological and immunological responses . However , further large-scale r and omized controlled clinical trials in this group of patients with advanced HIV infection are needed INTRODUCTION Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection . However , some concerns persist regarding antiviral efficacy , adherence , toxicity and resistance evolution in the long term . METHODS A total of 161 antiretroviral-naive HIV-1-infected patients were r and omized to receive stavudine/didanosine/efavirenz ( group A ) or zidovudine/lamivudine/ nelfinavir ( group B ) or to alternate between the two regimens every 3 months starting with regimen A ( group C ) . Antiviral efficacy , adherence , safety and tolerability were analysed every 12 weeks . RESULTS After 96 weeks , time to virological failure was significantly delayed in the alternating regimen compared with the st and ards of care regimens . Virological suppression was seen in 46 % , 48 % and 58 % of patients in groups A , B and C , respectively , in the intention-to-treat analysis and in 75 % , 76 % and 97 % in the on-treatment analysis ( A vs C : P=0.014 ; B vs C : P=0.016 ; A vs B : P=0.849 ) . At the end of the study , 94 % of patients in group A and 92 % in groups B and C reported an adherence greater than 95 % . Alternating therapy was associated with a similar impact on CD4 + counts in comparison with the st and ards of care regimens , as well as a lower mitochondrial DNA/nuclear DNA ( mtDNA/nDNA ) ratio decrease in the mitochondrial sub study performed on 37 patients . The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles . DISCUSSION Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations . Moreover , the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups . The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in st and ard regimens BACKGROUND To our knowledge , to date , no prospect i ve , r and omized , clinical trial has compared st and ard doses of efavirenz- and nevirapine-based antiretroviral therapy among patients with concurrent human immunodeficiency virus type 1 ( HIV-1 ) infection and tuberculosis ( TB ) who are receiving rifampicin . METHODS Rifampicin recipients with concurrent HIV-1 infection and TB were r and omized to receive antiretroviral therapy that included either efavirenz ( 600 mg per day ) or nevirapine ( 400 mg per day ) . Efavirenz and nevirapine concentrations at 12 h after dosing ( C12 ) were monitored at weeks 6 and 12 . CD4 + cell counts and HIV-1 RNA levels were assessed every 12 weeks . RESULTS One hundred forty-two patients were r and omized into 2 groups equally . The mean body weight of patients was 53 kg , the mean CD4 + cell count was 65 cells/mm3 , and the median HIV-1 RNA level was 5.8 log10 copies/mL. At weeks 6 and 12 , the mean C12 of efavirenz ( + /- st and ard deviation ) were 4.27+/-4.49 and 3.54+/-3.78 mg/L , respectively , and those for nevirapine were 5.59+/-3.48 and 5.6+/-2.65 mg/L , respectively . Interpatient variability in the efavirenz group was 2.3-fold greater than that in the nevirapine group ( coefficient of variation , 107 % vs. 47 % ) . At week 12 , 3.1 % of patients in the efavirenz group and 21.3 % in the nevirapine group had C12 values that were less than the recommended minimum concentrations ( odds ratio , 8.396 ; 95 % confidence interval , 1.808 - 38.993 ; P= .002 ) . Intention-to-treat analysis revealed that 73.2 % and 71.8 % of patients in the efavirenz and nevirapine groups , respectively , achieved HIV-1 RNA levels < 50 copies/mL at week 48 , with respective mean CD4 + cell counts of 274 and 252 cells/mm3 ( P > .05 ) . Multivariate analysis revealed that patients with low C12 values and those with a body weight < 55 kg were 3.6 and 2.4 times more likely , respectively , to develop all-cause treatment failure ( P < .05 ) . CONCLUSIONS Antiretroviral therapy regimens containing efavirenz ( 600 mg per day ) were less compromised by concomitant use of rifampicin than were those that contained nevirapine ( 400 mg per day ) in patients with concurrent HIV-1 infection and TB . Low drug exposure and low body weight are important predictive factors for treatment failure BACKGROUND The 2NN Study was a r and omised comparison of the non-nucleoside reverse-transcriptase inhibitors ( NNRTI ) nevirapine and efavirenz . METHODS In this multicentre , open-label , r and omised trial , 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily , nevirapine 200 mg twice daily , efavirenz 600 mg once daily , or nevirapine ( 400 mg ) and efavirenz ( 800 mg ) once daily , plus stavudine and lamivudine , for 48 weeks . The primary endpoint was the proportion of patients with treatment failure ( less than 1 log(10 ) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards , disease progression [ new Centers for Disease Control and Prevention grade C event or death ] , or change of allocated treatment ) . Analyses were by intention to treat . FINDINGS Treatment failure occurred in 96 ( 43.6 % ) of 220 patients assigned nevirapine once daily , 169 ( 43.7 % ) of 387 assigned nevirapine twice daily , 151 ( 37.8 % ) of 400 assigned efavirenz , and 111 ( 53.1 % ) of 209 assigned nevirapine plus efavirenz . The difference between nevirapine twice daily and efavirenz was 5.9 % ( 95 % CI -0.9 to 12.8 ) . There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 ( p=0.193 ) or the increases in CD4-positive cells ( p=0.800 ) . Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events , and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz . Of 25 observed deaths , two were attributed to nevirapine . INTERPRETATION Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy , so triple-drug regimens with either NNRTI are valid for first-line treatment . There are , however , differences in safety profiles . Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events OBJECTIVES To describe the longitudinal changes in hepatic function among HIV-infected tuberculosis ( TB ) patients receiving once-daily nevirapine (NVP)- or efavirenz (EFV)-based antiretroviral treatment ( ART ) along with rifampin-containing anti-TB treatment . METHODS This was a nested study within a r and omized clinical trial , taking place between May 2006 and June 2008 at the National Institute for Research in Tuberculosis , Chennai , India . Antiretroviral-naïve HIV-infected TB patients were initiated on an intermittent short-course regimen and r and omized to receive didanosine and lamivudine with either NVP ( 400 mg ) or EFV ( 600 mg ) once-daily . Blood was analyzed for alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , serum alkaline phosphatase ( SAP ) , and bilirubin at baseline , at ART initiation , fortnightly after ART initiation until 2 months , then monthly until 6 months and 6-monthly thereafter . RESULTS Of the 168 patients included ( 79 % men , median CD4 count 93 cells/mm3 , median viral load 242,000 copies/ml ) , 104 were on EFV-based ART and 64 on NVP-based ART . There was a small but statistically significant elevation in ALT and SAP at 2 weeks and AST at 6 weeks after ART initiation . The proportion of patients with rate-limiting toxicity of liver enzymes was small . None had treatment terminated because of hepatotoxicity . CONCLUSION Hepatotoxicity is not a major concern when HIV-infected TB patients , with normal baseline liver function initiate treatment for both infections simultaneously BACKGROUND The introduction of combination antiretroviral therapy and protease inhibitors has led to reports of falling mortality rates among people infected with HIV-1 . We examined the change in these mortality rates of HIV-1-infected patients across Europe during 1994 - 98 , and assessed the extent to which changes can be explained by the use of new therapeutic regimens . METHODS We analysed data from EuroSIDA , which is a prospect i ve , observational , European , multicentre cohort of 4270 HIV-1-infected patients . We compared death rates in each 6 month period from September , 1994 , to March , 1998 . FINDINGS By March , 1998 , 1215 patients had died . The mortality rate from March to September , 1995 , was 23.3 deaths per 100 person-years of follow-up ( 95 % CI 20.6 - 26.0 ) , and fell to 4.1 per 100 person-years of follow-up ( 2.3 - 5.9 ) between September , 1997 , and March , 1998 . From March to September , 1997 , the death rate was 65.4 per 100 person-years of follow-up for those on no treatment , 7.5 per 100 person-years of follow-up for patients on dual therapy , and 3.4 per 100 person-years of follow-up for patients on triple-combination therapy . Compared with patients who were followed up from September , 1994 , to March , 1995 , patients seen between September , 1997 , and March , 1998 , had a relative hazard of death of 0.16 ( 0.08 - 0.32 ) , which rose to 0.90 ( 0.50 - 1.64 ) after adjustment for treatment . INTERPRETATION Death rates across Europe among patients infected with HIV-1 have been falling since September , 1995 , and at the beginning of 1998 were less than a fifth of their previous level . A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments AIM For several years Nonnucleoside reverse transciptase inhibitors ( NNRTIs ) in antiretroviral therapy have been associated with hepatic side effects . Particularly the hepatotoxic potential of Nevirapine is well analysed today . We performed a prospect i ve , multicenter study to compare the hepatotoxicity of Efavirenz ( EFV ) with that of Nevirapine ( NVP ) and to investigate further risk factors . MATERIAL AND METHODS The study included HIV-1-infected patients from five clinics and private medical practice s in southwestern Germany who initiated an antiretroviral therapy with NVP or EFV between July 1998 and December 2001 . Among 296 patients in total , 151 received EFV and 145 received NVP . Laboratory tests during the course of treatment included liver enzymes , HIV-RNA and CD4 cell-count . Additionally , signs of clinical hepatitis were recorded . Hepatotoxicity was grade d in the manner of Sulkowsky et al. ( 2000 ) , who used a scale modified from that of the AIDS Clinical Trials Group . RESULTS Hepatitis C virus and hepatitis B virus were detected in 10.1 % and 4.1 % of patients , respectively . The overall rate of severe hepatotoxicity ( grade 3 to 4 elevations in aspartate aminotransferase and /or alanine aminotransferase ) was 2 of 151 ( 1.3 % ) in patients prescribed EFV and 3 of 145 ( 2.1 % ) in patients prescribed NVP . Mild-to-moderate hepatotoxicity ( grade 2 elevation ) was observed in 6.0 % ( EFV ) and 3.4 % ( NVP ) of patients . Incidence of mild-to-moderate and severe hepatotoxicity did not differ significantly between the study groups . 3 of 14 patients ( 2.1 % ) with grade 2 elevation of liver enzymes ( LEE ) and 4 of 5 patients ( 80 % ) with grade 3 to 4 LEE were symptomatic . Only risk factor for the development of mild-to-moderate hepatotoxicity was hepatitis C coinfection . CONCLUSION Increases of liver enzymes during therapy with NVP or EFV are not unusual , but are mostly mild-to-moderate and asymptomatic . LEE occurs just as frequent in patients prescribed EFV as in patients prescribed NVP Human immunodeficiency virus (HIV)-infected South African patients ( n=468 ) received blinded lamivudine or emtricitabine , stavudine , and either nevirapine or efavirenz ( based on screening viral load ) . Baseline characteristics were analyzed in univariate and multivariate regression , to identify risk factors for hepatotoxicity ( grade 3 or greater increase in serum aminotransferase levels ) . The occurrence of early hepatotoxicity was 17 % in the nevirapine group and 0 % in the efavirenz group and was balanced between the lamivudine and emtricitabine arms . Two subjects died of hepatic failure . Independent risk factors were body-mass index ( BMI ) < 18.5 , female sex , serum albumin level < 35 g/L , mean corpuscular volume > 85 fL , plasma HIV-1 RNA load < 20,000 copies/mL , aspartate aminotransferase level < 75 IU/L , and lactate dehydrogenase level < 164 IU/L. The use of nevirapine in female patients with a low BMI should be discouraged Twenty-six Thai HIV-infected children , aged 2 years or less were prospect ively enrolled to receive non-nucleoside reverse transcription inhibitor-based highly active antiretroviral therapy ( HAART ) . Twenty-two children ( 85 % ) had World Health Organization clinical stage 3 or 4 . The median baseline CD4 cell percentage and plasma HIV RNA were 17 % and 5.9 log 10 copies/mL , respectively . The median age at HAART initiation was 9.8 months ( range , 1.5–24.0 ) . One child died . The mean CD4 cell percentages at 24 , 48 , and 96 weeks of treatment were 26 % , 31 % , and 37 % , respectively . The proportions of children with virologic suppression ( < 400 copies/mL ) at week 24 and 48 were 14/26 ( 54 % ) and 19/26 ( 73 % ) , respectively . Non-nucleoside reverse transcription inhibitor-based HAART is safe and effective in HIV-infected young children in a re source -limited setting Objective To explore relationships between exposure to nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial . Methods The elimination rate constant of plasma HIV-1 RNA ( k ) was calculated during the first 2 weeks of treatment with nevirapine , zidovudine and didanosine in 51 antiretroviral-naive HIV-1-infected patients . The relationships between the value of k , the time to reach an undetectable HIV-1 RNA concentration in plasma ( < 20 copies/ml ) and the success of therapy after 52 weeks of treatment as dependent variables and the exposure to nevirapine , baseline HIV-1 RNA and baseline CD4 cell count as independent variables , were explored using linear regression analyses , proportional hazard models and logistic analyses , respectively . Results The value of k for HIV-1 RNA in plasma was positively and significantly associated with the mean plasma nevirapine concentration during the first 2 weeks of therapy ( P = 0.011 ) and the baseline HIV-1 RNA ( P = 0.008 ) . Patients with a higher exposure to nevirapine reached undetectable levels of HIV-1 RNA in plasma more rapidly ( P = 0.03 ) . From 12 weeks on , the median nevirapine plasma concentration was significantly correlated with success of therapy after 52 weeks ( P < 0.02 ) . Conclusions A high exposure to nevirapine ( in a twice daily regimen ) is significantly associated with improved virological response in the short as well as in the long term . These findings suggest that optimization of nevirapine concentration might be used as a tool to improve virological outcome in ( antiretroviral-naive ) patients treated with nevirapine BACKGROUND Nevirapine ( NVP ) can be safely and effectively administered once-daily but has not been assessed in human immunodeficiency virus (HIV)-infected patients with tuberculosis ( TB ) . We studied the safety and efficacy of once-daily NVP , compared with efavirenz ( EFV ; st and ard therapy ) ; both drugs were administered in combination with 2 nucleoside reverse-transcriptase inhibitors . METHODS An open-label , noninferiority , r and omized controlled clinical trial was conducted at 3 sites in southern India . HIV-infected patients with TB were treated with a st and ard short-course anti-TB regimen ( 2EHRZ(3)/4RH(3 ) ; [ 2 months of Ethambutol , Isoniazid , Rifampicin , Pyrazinamide / 4 months of Isoniazid and Rifampicin ] thrice weekly ) and r and omized to receive once-daily EFV at a dose of 600 mg or NVP at a dose of 400 mg ( after 14 days of 200 mg administered once daily ) with didanosine 250/400 mg and lamivudine 300 mg after 2 months . Sputum smears and mycobacterial cultures were performed every month . CD4 + cell count , viral load , and liver function test results were monitored periodically . Primary outcome was a composite of death , virological failure , default , or serious adverse event ( SAE ) at 24 weeks . Both intent-to-treat and per protocol analyses were done , and planned interim analyses were performed . RESULTS A total of 116 patients ( 75 % [ 87 patients ] of whom had pulmonary TB ) , with a mean age of 36 years , a median CD4 + cell count of 84 cells/mm(3 ) , and a median viral load of 310 000 copies/mL , were r and omized . At 24 weeks , 50 of 59 patients in the EFV group and 37 of 57 patients in the NVP group had virological suppression ( P = .024 ) . There were no deaths , 1 SAE , and 5 treatment failures in the EFV arm , compared with 5 deaths , 2 SAEs , and 10 treatment failures in the NVP arm . The trial was halted by the data and safety monitoring board at the second interim analysis . Favorable TB treatment outcomes were observed in 93 % of the patients in the EFV arm and 84 % of the patients in the NVP arm ( P = .058 ) . CONCLUSIONS Compared with a regimen of didanosine , lamivudine , and EFV , a regimen of once-daily didanosine , lamivudine , and NVP was inferior and was associated with more frequent virologic failure and death . Clinical Trials Registration . NCT00332306 Abstract Purpose : To compare long-term virologic , immunologic , and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens . Method : The FIRST study r and omized patients into three strategy arms : PI+NRTI , NNRTI+NRTI , and PI+NNRTI+NRTI . NNRTI was determined by optional r and omization ( NVP or EFV ) or by choice . For this r and omized sub study , the primary endpoint was HIV RNA > 50 copies/mL after 8 months or death . Genotypic resistance testing was done at virologic failure ( VF ; HIV RNA > 1000 copies/mL at or after 4 months ) . Results : 228 persons ( 111 r and omized to EFV , 117 to NVP ) were followed for median 5 years . Rates per 100 person years for the primary endpoint were 41.2 ( EFV ) and 42.8 ( NVP ; p = .59 ) . The percent of persons with HIV RNA < 50 copies/mL was similar throughout follow-up ( p = .24 ) , as were average increases in CD4 + cells ( p = .30 ) . 423 persons declining the sub study chose EFV ; 264 chose NVP . There were 915 persons in the combined cohort ( r and omized and choice ) . In the combined cohort , the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP . Conclusions : EFV-based regimens as initial therapy result ed in a lower risk of VF and VF with resistance than did NVP-based regimens , although immunologic and clinical outcomes were similar Abstract Objective : To compare the two nonnucleoside reverse transcriptase inhibitors ( NNRTIs ) when first introduced in an antiretroviral regimen , a prospect i ve open-label assessment of the frequency , severity , risk factors , and outcome of hepatotoxicity was performed . Method : Liver enzymes were followed-up during 18 months in patients who received efavirenz ( EFV ; 324 patients ) or nevirapine ( NVP ; 299 ) . Results : The two study groups were comparable , except for the lower baseline CD4 + count found in the EFV group . No differences were found when considering the type and duration of eventual prior anti-HIV therapy ; frequency and length of protease inhibitors , methadone , or anti-tubercular drug use ; HCV-HBV co-infection ; other hepatobiliary disorders ; and alcohol-drug abuse . The frequency of overall and first-month drug interruption proved similar in the two study groups . A hepatotoxicity characterized by at least a 2-fold increase of transaminases versus baseline was significantly linked with NVP , and the number of patients showing hepatotoxicity tended to a reduction in the EFV group . Also the time to peak transaminase alterations was shorter in the NVP group . All significant differences regarding liver-pancreatic toxicities were controlled per eventual baseline hepatobiliary-pancreatic diseases , HIV stage , and concurrent drug therapies . Discussion : Hepatotoxicity is a significant concern in the setting of antiretroviral-treated HIV disease . NVP-based HAART may be more hepatotoxic than EFV-based HAART , and a role is played by chronic liver disorders . Although concurrent hepatobiliary disorders and the possible hepatotoxicity of antiretrovirals do not represent contraindications to nonnucleoside inhibitor use , strict monitoring is recommended Abstract : An open-label , observational , prospect i ve 18-month survey was conducted to compare the efficacy and tolerability of the 2 available nonnucleoside reverse transcriptase inhibitors ( NNRTIs ) in all possible indications of current clinical practice . A broad range of clinical and laboratory variables accounting for drug efficacy and tolerability ( with special emphasis on metabolic and hepatic toxicity ) were measured in 287 evaluable patients treated with efavirenz , compared with 258 subjects taking nevirapine for 18 months . A separate efficacy analysis was performed in 154 antiretroviral-naive subjects , 298 patients experienced with 2–7 prior anti-HIV lines who ab and oned protease inhibitors ( PIs ) , and 103 subjects entering a salvage regimen containing at least 4 drugs , including PIs . Antiretroviral-naive patients experienced greater efavirenz activity at 3–12 months ( maximum HIV RNA drop = −2.4 log10 copies/mL ) , associated with a significantly higher rate of complete viral suppression , while immunologic results proved significant only after 6–9 months . When assessing experienced patients and those on rescue regimens , a similar and progressively blunted laboratory response was achieved , on the ground of a worse baseline virologic and immunologic profile , and duration of prior anti-HIV therapy . Both first-month ( 4.2 and 4.3 % for efavirenz and nevirapine , respectively ) and overall discontinuation rates ( 11.5 and 12 % , respectively ) proved similar , but a profound difference emerged as to the different spectrum of untoward events : central nervous system ( CNS ) disturbances , persisting metabolic abnormalities , and possibly gynecomastia and laboratory pancreatic abnormalities for efavirenz vs. immediate allergy and increased hepatotoxicity ( regardless of chronic infection with hepatitis B or C virus and methadone use ) for nevirapine . A limited virologic and immunologic advantage of efavirenz was observed in the first 12-month assessment of antiretroviral-naive patients , whereas all other examined situations did not disclose relevant efficacy differences between efavirenz and nevirapine throughout the 18-month comparison . Although the short- and long-term toxicity and withdrawal rates of the 2 drugs were comparable , the different pathways prompting allergic , metabolic , liver , and CNS disturbances observed with NNRTIs deserve careful investigation , to prevent toxicity of these relevant antiretroviral compounds Context The effects of the U.S. President 's Emergency Plan for AIDS Relief ( PEPFAR ) are unknown . Contribution Using data obtained from the United Nations , the authors detected a decrease in the number of HIV-related deaths in African countries receiving U.S. assistance after PEPFAR was introduced . Caution Many factors other than introduction of PEPFAR could have contributed to the observed findings . Implication The PEPFAR program seems to be having some favorable effects in African countries receiving AIDS assistance . The Editors Join the dialogue on health care reform . Comment on the perspectives published in Annals and offer ideas of your own . All thoughtful voices should be heard . Alleviating the burden of HIV in sub-Saharan Africa is one of the great challenges of our time ( 1 ) . Infection with HIV is the leading cause of death in Africa , and it is responsible for a reduction in life expectancy in many countries ( 2 ) . Available re sources to prevent and treat HIV in less developed countries have exp and ed more than 5-fold since the Declaration of Commitment on HIV/AIDS , adopted by the United Nations General Assembly in 2001 ( 3 , 4 ) , but the expansion has not been evenly distributed . Since 2003 , the U.S. President 's Emergency Plan for AIDS Relief ( PEPFAR ) provided the majority of its initial $ 18.8 billion budget to 15 focus countries12 of them in Africafor HIV and AIDS prevention , treatment , and care ( 5 , 6 ) . Although the criteria for selecting focus countries were not explicit , they were related to the burden of disease , the focus countries ' governmental commitment to fighting HIV , administrative capacity , and a willingness to partner with the U.S. government . Nearly half of PEPFAR 's re sources were spent on antiretroviral drugs and treatment infrastructure , and about one fifth was spent on prevention programs , of which one third was earmarked for abstinence-only programs . Through its various activities , PEPFAR aim ed to support the provision of life-saving antiretrovirals to 2 million people and prevent 7 million HIV infections in the focus countries within 5 years . Of the 3 major funders of HIV and AIDS programs ( PEPFAR ; The Global Fund to Fight AIDS , Tuberculosis , and Malaria ; and the World Bank ) , PEPFAR is unique in its distinctive approaches and disproportionate funding of a few countries ( 710 ) . In July 2008 , the U.S. Senate reauthorized PEPFAR with a $ 48 billion budget for the next 5 years , including a broader emphasis on strengthening health systems ( 11 ) . Leadership in the battle against HIV has been one of the United States ' most important legacies in Africa ( 12 , 13 ) . However , despite the substantial financial commitment and the important role PEPFAR plays abroad , no quantitative evaluation of the program 's outcomes has been completed . The original legislation m and ated a short-term evaluation that the Institute of Medicine completed in 2007 ( 14 ) . The report scrutinized the ability of PEPFAR to meet its targets for delivery of prevention , treatment , and care services in the focus countries , and it found that within 2 years , PEPFAR supported expansion of HIV and AIDS activities in the focus countries ; however , it did not evaluate health-related outcomes , such as HIV mortality , incidence , or prevalence . The number of human lives affected and the financial stakes make it essential to assess the impact of PEPFAR 's investment in Africa . Although the full impact of PEPFAR may not be felt for years , an ongoing evaluation of programmatic outcomes is central to the direction of future policies . Therefore , we quantitatively evaluated HIV-related outcomes in PEPFAR focus countries compared with other countries in sub-Saharan Africa with a generalized HIV epidemic . Methods Country Selection All countries of central , east , west , and south Africa and the isl and nations of Cape Verde , Comoros , Madagascar , Mauritius , So Tom and Prncipe , and Seychelles were eligible for this analysis . We excluded countries without epidemiologic data and those in which the HIV epidemic was not generalized . Generalized epidemic was defined as HIV prevalence of more than 1 % in antenatal clinics and a predominantly heterosexual mode of transmission ( 9 , 15 ) . We examined the countries that PEPFAR selected as focus countries as the intervention group and design ated all other sub-Saharan African countries with a generalized HIV epidemic as the control group . Data Sources The joint United Nations Programme on HIV/AIDS ( UNAIDS ) has monitored the Declaration of Commitment on HIV/AIDS by working with individual countries to measure the global epidemiology of HIV and AIDS ( 16 ) . We used country and year epidemiologic data obtained through UNAIDS from 1997 to 2007 as the outcome variables for this study . The UNAIDS determines the prevalence trends by using sentinel and population -based surveys . The prevalence estimates , vital registry data , and model-based calculations are then used to determine mortality and the number of people living with HIV . All the estimates are given uncertainty bounds that depend on the quality of the primary data and the strength of the assumptions used in the estimation process ( 17 ) . We obtained data on Global Fund allocation of re sources , population structure , governance indicators , life expectancy , and per capita gross domestic product from publicly available data bases ( 10 , 1820 ) . Study Periods and Outcomes We chose 2 study periods for this analysis : an early period , from 1997 to 2002 , before PEPFAR began , and a late period , from 2004 to 2007 , during PEPFAR 's activities . We excluded 2003 , the watershed year when PEPFAR 's operations were getting organized . Three outcomes were examined : HIV prevalence among adults 15 to 49 years of age , the number of deaths due to HIV or AIDS , and the number of adults living with HIV . We used these indicators as outcomes because they reflect the most consistent measures for cross-country comparisons available over time . The indicators are publicly available ( 21 ) . Statistical Analysis We compared trends of the epidemic outcomes between the focus and control countries during the early and late periods . We tested the hypothesis that the epidemic would show greater improvement ( or less worsening ) in the focus countries than in the control countries during the late period , after the onset of PEPFAR 's activities . We included the early period to separate the effects of PEPFAR from the natural course of the epidemic and any between-country differences ; that is , we wanted to compare not only the relative trends after PEPFAR began but also any changes in the relative trends before and during PEPFAR . We analyzed the trends by using a fixed-effects model for longitudinal data with fixed time and country effects ( 22 ) . We clustered by country and calculated robust st and ard errors because of the inherent bias in serially correlated data ( 23 ) . Year and PEPFAR design ation as a focus country , and an interaction term between them , were included as predictors in the unadjusted model . Except for prevalence rates , the outcomes we examined depend on the size of the population . To account for that , we examined the percentage change in the outcomes of interest by using log transformations of the outcomes ( 24 ) . For prevalence rates , we report the difference between the focus and control countries of the change in prevalence rather than the difference in percentage change . We report the interaction term coefficient , which estimates the difference in the trends between the focus and control countries . For example , a coefficient of 2 % in the number of deaths from 2004 to 2007 suggests that during that period , the percentage change in the number of deaths was 2 % less in the focus countries than in the control countries ( which means that deaths increased more slowly or decreased more rapidly , depending on the overall trend ) . We used Stata software , version 9.2 ( StataCorp , College Station , Texas ) , for all analyses and Stata 's xtreg comm and for the main regression . In adjusted analyses , we accounted for baseline HIV prevalence in 1997 , population size , life expectancy , per capita gross domestic product , the amount of funding from the Global Fund for HIV per capita , and 4 measures of governance from the World Bank 's Worldwide Governance Indicators : control of corruption , political stability , rule of law , and government effectiveness ( 20 ) . The indicators measure the quality of governance in more than 200 countries on the basis of 35 data sources from 32 organizations . They have been available since 1996 and are widely used in development research ( 25 , 26 ) . We also changed the model structure to allow for r and om year effects . Because none of these additional analyses changed the direction or significance of the relative effect of PEPFAR , we report the results of the unadjusted analyses . To account for uncertainty in the primary data and model estimates of the UNAIDS data , we did 2 sensitivity analyses ( 27 ) . First , we performed a Monte Carlo process where the outcome variable was drawn r and omly from a uniform distribution of values within the uncertainty bounds for each country-year observation , and the analysis was repeated 1000 times . We also performed a sensitivity analysis where we r and omly selected groups of focus countries and ran the analysis 1000 times to verify our analyses were not biased in favor of finding significant differences ( 23 ) . Role of the Funding Source This work was supported in part by a training grant from the Agency for Healthcare Research and Quality . The funding agency had no part in the design and conduct of the study ; collection , management , analysis , and interpretation of the data ; or preparation , review , or approval of the manuscript . Results Sample Characteristics We examined 12 PEPFAR focus countries and 29 control countries from sub-Saharan Africa for the analysis . Tables 1 and 2 show the selected countries and their baseline characteristics , respectively . The focus countries had a significantly BACKGROUND Children with HIV will be on antiretroviral therapy ( ART ) longer than adults , and therefore the durability of first-line ART and timing of switch to second-line are key questions . We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor ( NNRTI ) first-line ART and viral load switch criteria in children . METHODS In a r and omised open-label factorial trial , we compared effectiveness of two nucleoside reverse transcriptase inhibitors ( NRTIs ) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America . R and om assignment was by computer-generated sequentially numbered lists stratified by age , region , and by exposure to perinatal ART . Primary outcome was change in viral load between baseline and 4 years . Analysis was by intention to treat , which we defined as all patients that started treatment . This study is registered with IS RCT N , number IS RCT N73318385 . FINDINGS Between Sept 25 , 2002 , and Sept 7 , 2005 , 266 children ( median age 6.5 years ; IQR 2.8 - 12.9 ) were r and omly assigned treatment regimens : 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL ( PI-low ) , 65 protease inhibitor and switch at 30,000 copies per mL ( PI-higher ) , 68 NNRTI and switch at 1000 copies per mL ( NNRTI-low ) , and 67 NNRTI and switch at 30,000 copies per mL ( NNRTI-higher ) . Median follow-up was 5.0 years ( IQR 4.2 - 6.0 ) and 188 ( 71 % ) children were on first-line ART at trial end . At 4 years , mean reductions in viral load were -3.16 log(10 ) copies per mL for protease inhibitors versus -3.31 log(10 ) copies per mL for NNRTIs ( difference -0.15 log(10 ) copies per mL , 95 % CI -0.41 to 0.11 ; p=0.26 ) , and -3.26 log(10 ) copies per mL for switching at the low versus -3.20 log(10 ) copies per mL for switching at the higher threshold ( difference 0.06 log(10 ) copies per mL , 95 % CI -0.20 to 0.32 ; p=0.56 ) . Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group . NNRTI resistance was selected early , and about 10 % more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group . Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events ; both were balanced across r and omised groups . INTERPRETATION Good long-term outcomes were achieved with all treatments strategies . Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited , because the risk of selecting for NRTI and protease-inhibitor resistance is low . FUNDING Paediatric European Network for Treatment of AIDS ( PENTA ) and Pediatric AIDS Clinical Trials Group ( PACTG/IMPAACT ) The current st and ard of care for initial antiretroviral therapy is a combination of 2 nucleoside analogues with a third agent , a protease inhibitor ( PI ) , a non-nucleoside reverse transcriptase inhibitor or a third nucleoside analogue . Recent data heralding the arrival of potent PI-sparing regimens for initial anti-retroviral therapy and concerns regarding PI-related metabolic disturbances have led to significant shifts in treatment practice s. Protease inhibitor-sparing regimens with optimal antiviral activity may have several advantages over PI-based therapy for initial or prolonged therapy . These advantages include more convenient , non-food dependent dosing regimens , lower tablet volume , fewer drug interactions , central nervous system penetration and the maintenance of PIs as an option for second line therapy . However , no data currently exist directly comparing triple therapy regimens based on the three leading PI-sparing agents , efavirenz , nevirapine or abacavir . All these agents have been compared in r and omized controlled studies in treatment naïve patients to triple therapy with the PI indinavir . In these studies , similar responses to indinavir were observed with nevirapine or abacavir regimens , whereas superiority was observed with efavirenz . Limited data in high viral load patients treated with nevirapine based regimens currently exist . However , the superiority of efavirenz over indinavir based regimens was also observed in comparative data in this patient subset . PI-sparing approaches appear generally well tolerated with few individuals discontinuing in clinical studies due to adverse drug events . The majority of adverse events with efavirenz and nevirapine occur within the first month , are predictable and are manageable without therapy interruption . Similarly , apart from a rare ( 3 % ) hypersensitivity reaction , which requires therapy cessation without rechallenge , adverse effects with abacavir are uncommon Owing to their low toxicity , low price , and ease of use , efavirenz ( EFV ) and nevirapine ( NVP ) are frequently used as part of antiretroviral regimens for AIDS treatment . Several clinical trials have already studied their efficacy and tolerance . However , long-term observations of the effects of these drugs in patients are limited . We used data from a prospect i ve Senegalese cohort to analyze long-term tolerance and efficacy of these two drugs in a low-re sources setting . Patients were included if they started their therapy with EFV or NVP . They were censored after treatment discontinuation . The primary endpoint was the time to treatment discontinuation . Secondary endpoints included time to death , time to disease progression , occurrence of severe adverse effects , CD4 cell recovery , and virological response . Confounding factors were controlled using marginal structural models . The median follow-up time in both EFV and NVP arms was 48 months . The hazard ratio ( HR ) of drug discontinuation in the EFV arm vs. the NVP arm was 0.84 ( 0.34 ; 1.87 ) . There was a borderline difference in virological response [ HR 1.38 ( 0.999 ; 1.89 ) ] but no differences in time to death [ HR 1.15 ( 0.41 ; 3.24 ) ] , time to AIDS progression [ HR 1.25 ( 0.61 ; 2.58 ) ] , or time to increase in CD4 cell count above 500 cells/mm3 . Adverse effects were different between NVP and EFV , but long-term tolerance was good for both . This analysis provided further information on long-term tolerance and efficacy of EFV and NVP in a re source -limited setting |
2,373 | 23,353,036 | Hypothermia was associated with cerebrovascular disturbances on rewarming and possibly with pneumonia in adult patients .
Given the quality of the data currently available , no benefit of PTH on mortality or neurological morbidity could be identified . | This systematic review delineates the effect of primary therapeutic hypothermia ( PTH ) ( initiated on presentation of the patient ) on both mortality and neurological outcome in patients with traumatic brain injury .
The safety profile of the therapy is also assessed . | BACKGROUND The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury . We aim ed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury . METHODS The National Acute Brain Injury Study : Hypothermia II ( NABIS : H II ) was a r and omised , multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada . Patients with non-penetrating brain injury who were 16 - 45 years old and were not responsive to instructions were r and omly assigned ( 1:1 ) by a r and om number generator to hypothermia or normothermia . Patients r and omly assigned to hypothermia were cooled to 35 ° C until their trauma assessment was completed . Patients who had none of a second set of exclusion criteria were either cooled to 33 ° C for 48 h and then gradually rewarmed or treated at normothermia , depending upon their initial treatment assignment . Investigators who assessed the outcome measures were masked to treatment allocation . The primary outcome was the Glasgow outcome scale score at 6 months . Analysis was by modified intention to treat . This trial is registered with Clinical Trials.gov , NCT00178711 . FINDINGS Enrolment occurred from December , 2005 , to June , 2009 , when the trial was terminated for futility . Follow-up was from June , 2006 , to December , 2009 . 232 patients were initially r and omised a mean of 1·6 h ( SD 0·5 ) after injury : 119 to hypothermia and 113 to normothermia . 97 patients ( 52 in the hypothermia group and 45 in the normothermia group ) did not meet any of the second set of exclusion criteria . The mean time to 35 ° C for the 52 patients in the hypothermia group was 2·6 h ( SD 1·2 ) and to 33 ° C was 4·4 h ( 1·5 ) . Outcome was poor ( severe disability , vegetative state , or death ) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group ( relative risk [ RR ] 1·08 , 95 % CI 0·76 - 1·53 ; p=0·67 ) . 12 patients in the hypothermia group died compared with eight in the normothermia group ( RR 1·30 , 95 % CI 0·58 - 2·52 ; p=0·52 ) . INTERPRETATION This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury BACKGROUND Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies , but the results were not definitive . To study this issue , we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury . METHODS The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were r and omly assigned to be treated with hypothermia ( body temperature , 33 degrees C ) , which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling , or normothermia . All patients otherwise received st and ard treatment . The primary outcome measure was functional status six months after the injury . RESULTS The mean age of the patients and the type and severity of injury in the two treatment groups were similar . The mean ( + /-SD ) time from injury to r and omization was 4.3+/-1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group , and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours . The outcome was poor ( defined as severe disability , a vegetative state , or death ) in 57 percent of the patients in both groups . Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group ( P=0.79 ) . The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group . Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group . CONCLUSIONS Treatment with hypothermia , with the body temperature reaching 33 degrees C within eight hours after injury , is not effective in improving outcomes in patients with severe brain injury OBJECTIVE To observe the changes of evoked potentials after severe brain injury and the effect of mild hypothermia on acute severe brain injury . METHODS A total of 44 patients with severe closed head injury ( GCS 3 - 8 , admitted within 10 hours from injury ) admitted from May 1998 to March 1999 were selected for this study . All patients were admitted into the intensive care unit and divided into 2 groups , Group A ( GCS 3 - 5 ) and Group B ( GCS 6 - 8 ) . Patients were also r and omly assigned to either normothermia or hypothermia subgroups . Patients in the hypothermia group were cooled to 32 - 34 degrees C. Median nerve short-latency somatosensory evoked potentials ( SLSEP ) and brain stem auditory evoked potentials ( BAEP ) were recorded before cooling and 4 , 24 , 48 , 72 , 96 and 120 hours , respectively after cooling and temperature resuming . SLSEP and BAEP were measured at the same time in the normothermia group ( control group ) . The changes of evoked potentials ( EP ) were analyzed by statistical methods . RESULTS In the Group B , N(20 ) amplitudes in SLSEP and I/V amplitudes in BAEP after mild hypothermia treatment in the hypothermia group differed significantly from those in the control group ( P<0.05 ) . However , in the Group A , no significant difference in all parameters was found . CONCLUSIONS These results demonstrate that mild hypothermia treatment ( 32 - 34 degrees C ) in the Group B has a significant neuroelectrophysiological effect on severe brain injury . Nevertheless , the effect of mild hypothermia in the Group A is not apparent and needs further study ing Background Traumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union . Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming . A recent meta- analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly ( 1 ° C/4 hours ) . Previous experience with cooling also appears to be important if complications , which may outweigh the benefits of hypothermia , are to be avoided . Methods / design This is a pragmatic , multi-centre r and omised controlled trial examining the effects of hypothermia 32 - 35 ° C , titrated to reduce intracranial pressure < 20 mmHg , on morbidity and mortality 6 months after traumatic brain injury . The study aims to recruit 1800 patients over 41 months . Enrolment started in April 2010 . Participants are r and omised to either st and ard care or st and ard care with titrated therapeutic hypothermia . Hypothermia is initiated with 20 - 30 ml/kg of intravenous , refrigerated 0.9 % saline and maintained using each centre 's usual cooling technique . There is a guideline for detection and treatment of shivering in the intervention group . Hypothermia is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to maintain intracranial pressure < 20 mmHg . Intracranial hypertension is defined as an intracranial pressure > 20 mmHg in accordance with the Brain Trauma Foundation Guidelines , 2007 . Discussion The Eurotherm3235Trial is the most important clinical trial in critical care ever conceived by European intensive care medicine , because it was launched and funded by the European Society of Intensive Care Medicine and will be the largest non-commercial r and omised controlled trial due to the substantial number of centres required to deliver the target number of patients . It represents a new and fundamental step for intensive care medicine in Europe . Recruitment will continue until January 2013 and interested clinicians from intensive care units worldwide can still join this important collaboration by contacting the Trial Coordinating Team via the trial website http://www.eurotherm3235trial.eu . Trial registration Current Controlled Trials IS RCT Recent experimental studies have demonstrated that mild hypothermia at about 34 degrees C can be effective in the control of intracranial hypertension . A r and omized controlled study of mild hypothermia was carried out in 33 severely head-injured patients . All patients fulfilled the following criteria : 1 ) persistent intracranial pressure ( ICP ) greater than 20 mm Hg despite fluid restriction , hyperventilation , and high-dose barbiturate therapy ; 2 ) an ICP lower than the mean arterial blood pressure ; and 3 ) a Glasgow Coma Scale score of 8 or less . The patients were divided into two groups : one received mild hypothermia ( 16 patients ) and one served as a control group ( 17 patients ) . Mild hypothermia significantly reduced the ICP and increased the cerebral perfusion pressure . Eight patients ( 50 % ) in the hypothermia group and three ( 18 % ) in the control group survived ( p < 0.05 ) , while five ( 31 % ) in the hypothermia group and 12 ( 71 % ) in the control group died of uncontrollable intracranial hypertension ( p < 0.05 ) . In five patients in the hypothermia group , cerebral blood flow was measured by the hydrogen clearance method and arteriojugular venous oxygen difference was evaluated before and during mild hypothermia . Mild hypothermia significantly decreased the cerebral blood flow , arteriojugular venous oxygen difference , and cerebral metabolic rate of oxygen ( p < 0.01 ) . The results of this preliminary investigation suggest that mild hypothermia is a safe and effective method to control traumatic intracranial hypertension and to improve mortality and morbidity rates PURPOSE We investigated the effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy ( TBI ) . METHODS Eighty patients with severe TBI after unilateral craniotomy were r and omized into a therapeutic hypothermia group with the brain temperature maintained at 33 degrees C to 35 degrees C for 4 days , and a normothermia control group in the intensive care unit . Vital signs , intracranial pressure , serum superoxide dismutase level , Glasgow Outcome Scale scores , and complications were prospect ively analyzed . RESULTS The mean intracranial pressure values of the therapeutic hypothermia group at 24 , 48 , and 72 hours after injury were much lower than those of the control group ( 23.49 + /- 2.38 , 24.68 + /- 1.71 , and 22.51 + /- 2.44 vs 25.87 + /- 2.18 , 25.90 + /- 1.86 , and 24.57 + /- 3.95 mm Hg ; P = .000 , .000 , and .003 , respectively ) . The mean serum superoxide dismutase levels of the therapeutic hypothermia group at days 3 and 7 were much higher than those of the control group at the same time point ( 533.0 + /- 103.4 and 600.5 + /- 82.9 vs 458.7 + /- 68.1 and 497.0 + /- 57.3 mug/L , respectively ; P = .000 ) . The percentage of favorable neurologic outcome 1 year after injury was 70.0 % and 47.5 % , respectively ( P = .041 ) . Complications , including pulmonary infections ( 57.5 % in the therapeutic hypothermia group vs 32.5 % in the control group ; P = .025 ) were managed without severe sequelae . CONCLUSIONS Therapeutic mild hypothermia provides a promising way in the intensive care unit for patients with severe TBI after craniotomy Studies in adults have demonstrated improved outcomes using moderate hypothermia in the management of acute traumatic brain injury ( 1–6 ) . Moderate hypothermia may reduce secondary brain injury by reducing cerebral ischemia , edema , and tissue injury and by attenuating the production of excitatory amino acids ( 7–10 ) . A rat model utilizing mechanical traumatic brain injury and transient forebrain ischemia demonstrated that the peak time of vulnerability for posttraumatic secondary brain ischemia occurs within the first 24 hrs ( 11 ) . Another model demonstrated that apoptotic cells were detectable for up to 72 hrs after the initial brain injury , reaching a peak at approximately 24 to 48 hrs . In the animals treated with moderate hypothermia ( 32 ° C ) , the numbers of apoptotic cells were reduced , and DNA fragmentation was inhibited ( 12 ) . Studies evaluating the efficacy of moderate hypothermia in the management of acute traumatic brain injury have had variable entry criteria , time to entry , and duration of hypothermia . Shiozaki et al. ( 1 ) utilized hypothermia of 33.5–34.5 ° C for a minimum of 48 hrs after failure of conventional therapy , including barbiturate therapy . Tateishi et al. ( 13 ) induced hypothermia within 24 hrs and continued for a mean duration of 68 hrs ( range , 20–118 hrs ) . Marion et al. ( 2 , 3 ) reported a mean time of 10 hrs from injury to hypothermia that was maintained for 24 hrs . Clifton et al. ( 5 , 14 ) induced cooling within 6 hrs of injury and maintained hypothermia for 48 hrs . Although hypothermia has been utilized for 40 yrs in the management of traumatic brain injury in adults ( 15–17 ) , reports of its use in children are few ( 18 ) . Due to the paucity of information in the pediatric population and animal data that suggest that significant secondary brain injury and apoptosis occur 24 to 48 hrs after brain injury ( 11 , 12 ) , we opted for a study design similar to that of Clifton et al. ( 5 , 14 ) . We hypothesized that in children with acute traumatic brain injury , 48 hrs of moderate hypothermia ( 32– 34 ° C , initiated within 6 hrs of injury ) , in conjunction with st and ard conventional management of intracranial hypertension , would result in decreased severity and duration of intracranial hypertension and a favorable cerebral physiology compared with patients treated with normothermia . Furthermore , we hypothesized that this duration of moderate hypothermia would be safe and not associated with serious adverse clinical events , such as bleeding , electrolyte disturbances , pneumonia , or other infections Aim of this study was to examine the hypothesis that only a subgroup of patients with lesser primary brain damage after severe head injury may benefit from therapeutic hypothermia . We prospect ively analysed 72 patients with severe head injury , r and omized into groups with ( n = 37 ) and without ( n = 35 ) hypothermia of 34 degrees C maintained for 72 hours . The influence of hypothermia on ICP , CPP and neurological outcome was analysed in the context of the extent of primary brain damage . Patients with normothermia and primary lesions ( n = 17 ) values : GCS on admission 5 ( median ) , ICP 18.9 ( mean ) , CPP 73 ( mean ) , GOS 4 ( median ) . Patients with normothermia and extracerebral hematomas ( n = 20 ) : GCS 4 , ICP 16 , CPP 71 , GOS 3 . Patients with hypothermia and primary lesions ( n = 21 ) : GCS 4,62 , ICP 10 , 81 , CPP 78,1 , GOS 4 . Patients with hypothermia and extracerebral hematomas ( n = 14 ) : GCS 5 , ICP 13.2 , CPP 78 , GOS 5 . Hypothermia decreased ICP and increased CPP regardless of the type of brain injury . Hypothermia was not able to improve outcome in patients with primary brain lesions but this pilot study suggests that it significantly improves outcome in patients with extracerebral hematomas Forty-six patients with severe nonpenetrating brain injury [ Glasgow Coma Scale ( GCS ) 4 - 7 ] were r and omized to st and ard management at 37 degrees C ( n = 22 ) and to st and ard management with systemic hypothermia to 32 to 33 degrees C ( n = 24 ) . The two groups were balanced in terms of age ( Wilcoxon 's rank sum test , p > 0.95 ) , r and omizing GCS ( chi-square test , p = 0.54 ) , and primary diagnosis . Cooling was begun within 6 h of injury by use of cooling blankets . Metocurine and morphine were given hourly during induction and maintenance of hypothermia . Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications . Seizure incidence was lower in the hypothermia group ( Fisher 's exact text , p = 0.019 ) . Sepsis was seen more commonly in the hypothermia group , but difference was not statistically significant ( chi-square test ) . Mean Glasgow Outcome Scale ( GOS ) score at 3 months after injury showed an absolute increase of 16 % ( i.e. , 36.4 - 52.2 % ) in the number of patients in the Good Recovery/Moderate Disability ( GR/MD ) category as compared with Severe Disability/Vegetative/Dead ( SD/V/D ) ( chi-square test , p > 0.287 ) . Based on evidence of improved neurologic outcome with minimal toxicity , we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted OBJECTIVE : To determine whether moderate hypothermia ( HYPO ) ( 32–33 ° C ) begun in the early period after severe traumatic brain injury ( TBI ) and maintained for 48 hours is safe compared with normothermia ( NORM ) ( 36.5–37.5 ° C ) . METHODS : After severe ( Glasgow Coma Scale score ≤8 ) nonpenetrating TBI , 48 children less than 13 years of age admitted within 6 hours of injury were r and omized after stratification by age to moderate HYPO ( 32–33 ° C ) treatment in conjunction with st and ardized head injury management versus NORM in a multicenter trial . An additional 27 patients were entered into a parallel single-institution trial of excluded patients because of late transfer or consent ( delayed in transfer > 6 h but within 24 h of admission ) , unknown time of injury ( e.g. , child abuse ) , and adolescence ( e.g. , aged 13–18 yr ) . Assessment s of safety included mortality , infection , coagulopathy , arrhythmias , and hemorrhage as well as ability to maintain target temperature , mean intracranial pressure ( ICP ) , and percent time of ICP less than 20 mm Hg during the cooling and subsequent rewarming phases . Additionally , assessment s of neurocognitive outcomes were obtained at 3 and 6 months of follow-up . RESULTS : Moderate HYPO after severe TBI in children was found to be safe relative to st and ard management and NORM in children of all ages and in children with delay of initiation of treatment up to 24 hours . Although there was decreased mortality in HYPO in both studies , there was an increased potential for arrhythmias with HYPO , although they were manageable with fluid administration or rewarming . Additionally , there was a reduction in mean ICP during the first 72 hours after injury in both studies , although rebound ICP elevations in HYPO compared with those in NORM were noted for up to 10 to 12 hours after rewarming . Although functional outcome at 3 or 6 months did not differ between treatment groups , functional outcome tended to improve from the 3- to 6-month cognitive assessment in HYPO compared with NORM , although the sample size was too small for any definitive conclusions . CONCLUSION : HYPO is likely a safe therapeutic intervention for children after severe TBI up to 24 hours after injury . Further studies are necessary and warranted to determine its effect on functional outcome and intracranial hypertension Abstract Objective . To examine the effect of controlled moderate hypothermia on thyroid response in head-injured patients . Design . Prospect i ve , controlled , r and omized study . Setting . University hospital intensive care unit ( ICU ) . Patients . Twenty-eight patients with severe blunt head injury ( Glasgow Coma Scale ≤9 ) . Intervention . Patients were r and omly assigned to a hypothermia or a normothermia group . Hypothermia ( 32–33 ° C ) was induced within 8 h after trauma and maintained for a mean of 36 h. All patients were se date d and mechanically ventilated . Measurements and results . Thyroid-stimulating hormone ( TSH ) , free and total triiodothyronine ( FT3/TT3 ) , reverse triiodothyronine ( RT3 ) and thyroxine ( FT4/TT4 ) were measured during the hypothermia or corresponding normothermia period , after regaining normothermia and 4–6 days later . Of 28 patients included in the study , 11 subjects were treated with hypothermia and 13 patients with normothermia . Four patients had to be excluded . In both groups , serum concentrations of TT3 and FT3 were just below the lower normal range whereas RT3 serum concentrations were near the upper limit of the normal range . TSH serum concentrations were not increased . No statistically significant intra- or inter-group differences were observed . Conclusions . Thyroid hormone patterns during moderate hypothermia in head-injured patients did not differ from the well known " low T3 state " which is observed in other forms of severe illness OBJECT The criteria for the use of mild hypothermia ( 34 degrees C ) in severely head injured patients have not been st and ardized . A prospect i ve r and omized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure ( ICP ) . METHODS At 11 medical centers , 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided r and omly into two groups : the mild hypothermia group ( HT group , 45 patients ) and the normothermia group ( NT group , 46 patients ) . Patients in the HT group were exposed to mild hypothermia ( 34 degrees C ) for 48 hours , followed by rewarming at 1 degrees C per day for 3 days , whereas patients in the NT group were exposed to normothermia ( 37 degrees C ) for 5 days . The two groups were similar with respect to prognostic factors , and there was no difference in clinical outcome at 3 months postinjury . During treatment , there was a significantly greater use of neuromuscular blocking agents in the HT group ( p = 0.011 ) . During the initial 2 weeks postinjury , the incidences of pneumonia , meningitis , leukocytopenia , thrombocytopenia , hypernatremia , hypokalemia , and hyperamylasemia were significantly higher in the HT than in the NT group ( p < 0.05 ) . CONCLUSIONS Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients Objective To examine the levels of thromboxane B2 ( TXB2 ) and 6-keto prostagl and in F1&agr ; ( 6-keto PGF1&agr ; ) production in arterial and internal jugular bulb sera in patients with traumatic brain injury ( TBI ) . TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites . Design A prospect i ve , r and omized study . Setting The intensive care unit of a medical university hospital . Interventions Twenty-six ventilated TBI patents ( Glasgow Coma Scale score on admission , ≤8 points ) were divided r and omly into two groups : a hypothermic group ( n = 15 ) , in which the patients were cooled to 32 to 33 ° C after being giving vecuronium , midazolam , and buprenorphine ; and a normothermic group ( n = 11 ) , in which the patients ’ body temperature was controlled at 36 to 37 ° C by surface cooling using the same treatment as the hypothermic group . Body temperature control including normothermia was started 3 to 4 hrs after injury . The duration of hypothermia usually lasted for 3 to 4 days , after which the patients were rewarmed at a rate of approximately 1 ° C per day . Measurements and Main Results Blood sampling for TXB2 and 6-keto PGF1&agr ; was started shortly after admission in both groups . Arterial TXB2 levels on admission in both groups were elevated remarkably , but not 6-keto PGF1&agr ; , thereby causing an imbalance of the prostanoids after injury . In the normothermic group , TXB2 decreased transiently , but this prostanoid increased again 3 days after the injury . In the hypothermic group , such prostanoid differences disappeared shortly after therapy , and the condition was sustained for 10 days . Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera , which may reflect reduced cerebral prostanoid production . The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group ( p = .04 ) . Conclusion The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI , thereby attenuating an imbalance of thromboxane A2 and prostagl and in I2 . However , it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI An extensive literature suggests that there are minimal complications of systemic hypothermia in humans at and above 30 degrees C for periods of several days . Intracranial hemorrhage has been found to complicate profound hypothermia ( 10 - 15 degrees C ) , and ventricular arrhythmias occur at temperatures below 30 degrees C. Our initial clinical studies were with 21 patients undergoing elective craniotomy cooled to 30 - 32 degrees C for 1 - 8 h ( mean 4 h ) . Hypothermia was induced by surface cooling with water blankets . No complications were found . Among 11 patients with severe brain injury , cooling to levels below 32 degrees C was associated with ventricular arrhythmias in 1 patient and atrioventricular block in 1 patient . Asymptomatic hypokalemia was found routinely and treated with potassium replacement . No intracranial hemorrhage or other complications were found . With surface cooling , intravascular temperature dropped at 1.6 degrees C/h . Based on the safety of surface cooling to a core temperature of 32 degrees C for 48 h , we are conducting a r and omized study of this level of hypothermia in patients with severe brain injury , cooled within 6 h of injury BACKGROUND The therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury were studied . METHODS All 396 patients with severe head injury [ Glasgow Coma Scale score ( GCS ) equal to or less than 8 on admission ] were r and omly divided into the hypothermic group ( 198 cases ) and the control group ( 198 cases ) . Hypothermia was induced within 24 hours of injury . Rewarming began 1 to 7 days ( average 62.4 + /- 27.6 h ) after the rectal temperature ( RT ) reached 32.0 to 35.0 degrees C. Meanwhile , the vital signs , intracranial pressure ( ICP ) , blood gas values , blood electrolytes , brain tissue oxygen pressure ( P(bt)O2 ) , brain tissue temperature ( BT ) , cerebral blood flow ( CBF ) , and jugular venous oxygen saturation ( S(jv)O2 ) were measured . The rectal temperature of control patients was induced to 36.5 to 37.0 degrees C. According to GOS , the prognosis of the patients was evaluated . RESULTS In comparison with control group , during mild hypothermia the high level of ICP , hyperglycemia and blood lactic acid significantly decreased ( p < 0.05 ) and cerebral flow improved dominantly . The vital signs , blood gas values , and blood electrolytes did not change significantly . Decreased mortality and good recovery were also found in hypothermia group . CONCLUSIONS Mild hypothermia is safe and effective for preventing brain damage on patients with severe head injury , as well as reducing mortality and improving the prognosis . It is important to monitor P(bt)O2 , BT , CBF , and S(jv)O2 in hypothermic therapy BACKGROUND Infectious complications are among the most serious problems that occur in severely head-injured patients treated with mild hypothermia . The mechanism underlying the susceptibility to infection has not been clarified . Heat shock protein ( HSP ) 60 has been reported to play an essential role in innate immunity . Thus , we conducted a study to clarify the impact of mild hypothermia on the expression of HSPs in polymorphonuclear leukocytes ( PMNLs ) in severely head-injured patients . METHODS Between September 1997 and November 1999 , 17 severely head-injured patients with a Glasgow Coma Scale score of 8 or less at admission in whom intracranial pressure could be maintained below 20 mm Hg by conventional therapy were r and omly assigned to two treatment groups : a mild hypothermia group ( HT group , nine patients ) and a normothermia group ( NT group , eight patients ) . The HT group was subjected to mild hypothermia ( intracranial temperature , 34 degrees C ) for 48 hours followed by rewarming at a rate of 1 degrees C per day for 3 days , whereas the NT group was subjected to normothermia ( intracranial temperature , 37 degrees C ) for 5 days . Blood sample s were serially obtained at three time points ; days 0 to 1 , days 2 to 5 , and days 6 to 14 after head injury . We measured the expression of HSP27 , HSP60 , HSP70 , and HSP90 by flow cytometry . RESULTS The two groups were similar with respect to prognostic factors , and there was no difference in clinical outcome . The expression of PMNL HSP60 in the HT group was significantly lower in all three time periods compared with that in the NT group ( p < 0.05 ) , whereas expression of the other HSPs did not differ significantly between the groups . The incidence of infectious complications was significantly increased in the HT group over that in the NT group ( p < 0.05 ) . In in vitro studies , PMNLs from 10 healthy volunteers were incubated at 37 degrees C , 34 degrees C , or 26 degrees C for 1 hour with sodium arsenite ( 100 micromol/L ) , an HSP inducer . The expression of HSP60 at 26 degrees C and 34 degrees C was significantly lower than that at 37 degrees C ( p < 0.05 ) , whereas expression of the other HSPs did not differ significantly at 26 degrees C , 34 degrees C , or 37 degrees C. CONCLUSION Mild hypothermia reduces the expression of HSP60 in PMNLs from severely head-injured patients . Thus , mild hypothermia may suppress innate immunity |
2,374 | 22,682,572 | There is strong evidence that some , but not all , psychosocial treatments are effective in treating alcohol problems .
Those with the strongest empirical support are motivational enhancement therapy , various cognitive-behavioural interventions , and brief interventions .
When these modalities have been compared with one another in well- design ed clinical trials , they have been shown to be of comparable effectiveness . | Our objectives were to review the effectiveness of psychosocial modalities in the treatment of alcohol use disorders and problems , and to examine the impact of therapists on treatment outcome , the evidence on best practice s for comorbid conditions , and the evidence on treatment matching . | AIMS This study tested the hypothesis that patients with more severe substance use disorders ( SUDs ) at intake respond better when treated in more structured and intensive setting s ( i.e. in-patient/residential versus out-patient ) , whereas patients with less severe SUD problems have similar outcomes regardless of treatment setting . DESIGN , SETTING AND PARTICIPANTS Up to 50 new patients were selected r and omly from each of a r and om and representative sample of 50 Department of Veterans Affairs ( VA ) SUD treatment programs ( total n = 1917 patients ) , and were followed-up an average of 6.7 months later ( n = 1277 ) . MEASURES Patients completed a brief self-report version of the Addiction Severity Index ( ASI ) at baseline and at follow-up . FINDINGS In mixed-model regression analyses , baseline substance use severity predicted follow-up substance use severity and there were no main effects of treatment setting . However , interaction effects were found , such that more severe patients experienced better alcohol and drug outcomes following in-patient/residential treatment versus out-patient treatment ; on the other h and , patients with lower baseline ASI drug severity had better drug outcomes following out-patient treatment than in-patient treatment . Treatment setting was unrelated to alcohol outcomes in patients with less severe ASI alcohol scores . CONCLUSIONS Results provide some support to the matching hypothesis that for patients who have higher levels of substance use severity at intake , treatment in in-patient/residential treatment setting s is associated with better outcomes than out-patient treatment . More research needs to be conducted before in-patient/residential setting s are further reduced as a part of the SUD continuum of care in the United States Objective : To determine the prevalence of concurrent personality disorders ( PDs ) among alcoholic men and women seeking outpatient treatment , and to examine their effect on the course of alcohol treatment . Method : Patients with alcohol use disorders ( n = 165 ) were assessed by clinical and semi-structured interviews , as well as self-report scales , to measure levels of psychological distress , impulsivity , social functioning , and addiction severity at treatment intake . PD diagnoses were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Personality Disorder ( SCID-II ) . Course in treatment was monitored prospect ively for 12 weeks . Results : Using the results of the SCID-II ( n = 138 ) , the sample was divided into 3 groups — that is , no PD 41 % ( n = 57 ) , Cluster B PD 32 % ( n = 44 ) , and other PD 27 % ( n = 37 ) . The 3 groups did not differ in their alcohol use severity at intake . However , the Cluster B PD group achieved alcohol milestones at a younger age . Subjects with a PD had more severe psychological and social problems at intake . The Cluster B PD group showed significantly higher levels of impulsivity at intake , greater likelihood of early treatment dropout , and quicker times to first slip and to relapse . Conclusions : This study supports the high prevalence of concurrent PDs , particularly Cluster B PDs , among treatment-seeking alcoholics . The relation between observed high levels of impulsivity and worse course in early alcohol treatment among people with a Cluster B PD merits further investigation BACKGROUND Our initial attempts to " match " substance-abuse patients from an employee assistance program to an optimal setting or program failed . Scientifically , we found no differential predictors of better outcomes by setting or program . From a practical perspective , it was impossible to place patients in the intended programs . This led to a second study , design ed to identify specific patient problems and match professional services to those problems within each of the 4 programs . METHODS Ninety-four new patients admitted to 4 substance-abuse treatment programs were r and omly assigned to st and ard treatment and treated in the usual manner or were assigned to " matched " services , in which patients received at least 3 professional sessions directed at their important employment , family , or psychiatric problems . RESULTS Matched patients stayed in treatment longer , were more likely to complete treatment , and had better posttreatment outcomes than did the st and ard patients treated in the same programs . CONCLUSIONS For logistical , financial , and clinical reasons , it is improbable that patients will be matched to specific types of programs . However , within any program , it is possible and practical to match appropriate services to patients ' specific treatment problems . This strategy was clinical ly and administratively practical , attractive to patients , and responsible for a 20 % to 30 % increase in the effectiveness of this substance-abuse treatment system 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 AIMS Post-discharge monitoring and early reintervention have become st and ard practice when managing numerous chronic conditions . These two experiments tested the effectiveness of recovery management checkup ( RMC ) protocol s for adult chronic substance users . INTERVENTION RMC included quarterly monitoring ; motivational interviewing to provide personalized feedback and to resolve ambivalence about substance use ; treatment linkage , engagement and retention protocol s to increase the amount of treatment received . PARTICIPANTS AND SETTING Recruited from sequential addiction treatment admissions , participants in the two experiments were , on average , 36 and 38 years of age , mainly female ( 59 % versus 46 % ) , African American ( 85 % versus 80 % ) and met past-year criteria for dependence ( 87 % versus 76 % ) . DESIGN Participants in both experiments were assigned r and omly to the RMC or control condition and interviewed quarterly for 2 years . MEASUREMENT The Global Appraisal of Individual Needs ( GAIN ) was the main assessment instrument . FINDINGS RMC participant outcomes were better than control participants in both experiments . Effect sizes were larger in the second experiment in terms of reducing days to readmission ( Cohen 's d = 0.41 versus d = 0.22 ) , successive quarters in the community using substances ( d = -0.32 versus -0.19 ) , past-month symptoms of abuse/dependence ( d = -0.23 versus -0.02 ) and increasing the days of abstinence over 2 years ( d = + 0.29 versus 0.04 ) . CONCLUSION RMC , which provided ongoing monitoring and linkage , is feasible to conduct and is effective for adults with chronic substance dependence This study reports 3-year outcomes for clients who had been treated in the five outpatient sites of Project MATCH , a multisite clinical trial design ed to test a priori client treatment matching hypotheses . The main purpose of this study was to characterize the status of the matching hypotheses at the 3-year follow-up . This entailed investigating which matching findings were sustained or even strengthened across the 3-year study period , and whether any hypotheses that were not supported earlier eventually emerged at 3 years , or conversely , whether matching findings discerned earlier dissipated at this later time . This research also examines the prognostic effects of the client matching attributes , characterizes the overall outcomes at 37 to 39 months , and explores differential effects of the three treatments at extended follow-up . With regard to the matching effects , client anger demonstrated the most consistent interaction in the trial , with significant matching effects evident at both the 1-year and 3-year follow-ups . As predicted , clients high in anger fared better in Motivational Enhancement Therapy ( MET ) than in the other two MATCH treatments : Cognitive-Behavioral Therapy ( CBT ) and Twelve-Step Facilitation ( TSF ) . Among subjects in the highest third of the anger variable , clients treated in MET had on average 76.4 % abstinent days , whereas their counterparts in the other two treatments ( CBT and TSF ) had on average 66 % abstinent days . Conversely , clients low in anger performed better after treatment in CBT and TSF than in MET . Significant matching effects for the support for drinking variable emerged in the 3-year outcome analysis , such that clients whose social networks were more supportive of drinking derived greater benefit from TSF treatment than from MET . Among subjects in the highest third of the support for drinking variable , TSF participants were abstinent 16.1 % more days than MET participants . At the lower end of this variable , difference in percent days abstinent between MET and TSF was 3 % , with MET clients having more abstinent days . A significant matching effect for psychiatric severity that appeared in the first year posttreatment was not observed after 3 years . Of the 21 client attributes used in testing the matching hypotheses , 11 had prognostic value at 3 years . Among these , readiness-to-change and self-efficacy emerged as the strongest predictors of long-term drinking outcome . With regard to the overall outcomes , the reductions in drinking that were observed in the first year after treatment were sustained over the 3-year follow-up period : almost 30 % of the subjects were totally abstinent in months 37 to 39 , whereas those who did report drinking nevertheless remained abstinent an average of two-thirds of the time . As in the 1-year follow-up , there were few differences among the three treatments , although TSF continued to show a possible slight advantage 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 Over 50 % of people with a severe mental illness also use illicit drugs and /or alcohol at hazardous levels . This review is based on the findings of 25 r and omized controlled trials which assessed the effectiveness of psychosocial interventions , offered either as one-off treatments or as an integrated or nonintegrated program , to reduce substance use by people with a severe mental illness . The findings showed that there was no consistent evidence to support any one psychosocial treatment over another . Differences across trials with regard to outcome measures , sample characteristics , type of mental illness and substance used , setting s , levels of adherence to treatment guidelines , and st and ard care all made pooling results difficult . More quality trials are required that adhere to proper r and omization methods ; use clinical ly valuable , reliable , and vali date d measurement scales ; and clearly report data , including retention in treatment , relapse , and abstinence rates . Future trials of this quality will allow a more thorough assessment of the efficacy of psychosocial interventions for reducing substance use in this challenging population This study examines the linkages in the treatment process chains that are thought to underlie two prevalent approaches to substance abuse treatment , traditional 12-Step treatment and cognitive-behavioral treatment . The focus is on the " proximal outcomes " specified by the two treatment approaches and their relation to " ultimate " substance use outcomes assessed at a 1-year follow-up . A total of 2687 men who received treatment in 15 Department of Veterans Affairs substance abuse treatment programs were assessed at treatment entry , at or near discharge , and at a 1-year follow-up . Based on the results of factor analyses , composite proximal outcomes variables were constructed to assess 12-Step cognitions , 12-Step behaviors , cognitive-behavioral beliefs , substance-specific coping , and general coping . Correlation analyses indicated that some of the proximal outcome composites assessed at treatment discharge were linked to 1-year outcomes , but the relationships were weak ( r = .09 to .15 ) . At follow-up , the cross-sectional relationships between the proximal outcome composites and two substance use outcomes were stronger , but still modest in magnitude ( r = .16 to .39 ) . The weak predictive findings suggest some mechanism is needed to sustain treatment-induced change on proximal outcomes so that positive ultimate outcomes can be achieved more frequently . In this regard , participation in continuing care was associated with enhanced maintenance of treatment gains on proximal outcomes . However , the modest cross-sectional relationships between proximal and substance use outcomes at follow-up suggest that the theories on which 12-Step and cognitive-behavioral substance abuse treatments are based are not sufficiently comprehensive The impact of the counselor in substance abuse rehabilitation has been question ed . The unexpected resignations of two counselors provided a natural opportunity to examine the effects of counselor assignment in a methadone maintenance treatment program with the effects of the medication philosophy , program rules , and supplementary services held constant . Sixty-one patients who had been assigned to these two counselors were assigned to four other counselors in a virtually r and om manner . It was reasoned that if the new counselor had relatively little impact , then there would be little difference in performance from pre to posttransfer or among the four caseloads during the 6-month period following the transfer . Performance measures included urinalysis results , methadone dosage , prescriptions for psychotropic medications , employment , and arrest rates . Results indicated statistically significant and clinical ly meaningful differences in the posttransfer performance of the four caseloads . One counselor significantly reduced the average methadone dose of his/her caseload as well as the number of patients prescribed ancillary medications , while concurrently reducing positive urine tests , unemployment and arrests . In contrast , another counselor significantly increased the average methadone dose in his/ her caseload but still showed increases in positive urine tests and unemployment . As has been found in prior studies , background and formal education differences among the counselors were not related to the observed performance differences . However , differences in the content and process of counseling among the counselors were associated with the differences in patient outcome . These process differences are discussed in relation to earlier studies of professional psychotherapy Abstract Objective To compare the effectiveness of social behaviour and network therapy , a new treatment for alcohol problems , with that of the proved motivational enhancement therapy . Design Pragmatic r and omised trial . Setting Seven treatment sites around Birmingham , Cardiff , and Leeds . Participants 742 clients with alcohol problems ; 689 ( 93.0 % ) were interviewed at three months and 617 ( 83.2 % ) at 12 months . Interventions Social behaviour and network therapy and motivational enhancement therapy . Main outcome measures Changes in alcohol consumption , alcohol dependence , and alcohol related problems over 12 months . Results Both groups reported substantial reductions in alcohol consumption , dependence , and problems , and better mental health related quality of life over 12 months . Between groups we found only one significant difference in outcome , probably due to chance : the social network group showed significantly better physical health at three months . Non-significant differences at 12 months in the motivational group relative to the social network group included : the number of drinks consumed per drinking day had decreased by an extra 1.1 ( 95 % confidence interval −1.0 to 3.2 ) ; scores on the Leeds dependence question naire had improved by an extra 0.6 ( −0.7 to 2.0 ) ; scores on the alcohol problems question naire had improved by an extra 0.5 ( −0.4 to 1.4 ) ; but the number of days abstinent from drinking had increased by 1.2 % less ( −4.5 % to 6.9 % ) . Conclusion The novel social behaviour and network therapy for alcohol problems did not differ significantly in effectiveness from the proved motivational enhancement therapy This study examined data collected on over 5,000 clients seen by 71 therapists over a 6-year period in a University Counseling Center . Clients were given the Outcome Question naire-45 ( OQ-45 ) on a session-by-session basis to track their treatment response . Data were also collected on therapists ' theoretical orientation , years of experience , gender , and type of training . Data were analyzed using hierarchical linear modeling ( HLM ) to see if general therapist traits ( i.e. , theoretical orientation , type of training ) accounted for differences in clients ' rate of improvement . Data were then analyzed , again using HLM with therapists as a fixed effect , to compare individual therapists to see if there were significant differences in the efficiency of treatment . In addition , pre- minus posttest OQ-45 scores were examined to see if there were differences in the overall outcome of clients . There was a significant amount of variation among therapists ' clients ' rates of improvement . Therapist feedback reports were generated to summarize client outcome for individual providers in contrast to center averages and in an attempt to improve client outcome This study examined the relatively unexplored contribution of the therapist 's performance in determining outcomes of treatment . Nine therapists were studied : three performed supportive-expressive psychotherapy ; three , cognitive-behavioral psychotherapy ; and three , drug counseling . Profound differences were discovered in the therapists ' success with the patients in their case loads . Four potential determinants of these differences were explored : patient factors ; therapist factors ; patient-therapist relationship factors ; and therapy factors . Results showed that patient characteristics within each case load ( after r and om assignments ) were similar and disclosed no differences that would have explained the differences in success ; therapist 's personal qualities were correlated with outcomes but not significantly ( mean r = .32 ) ; an early-in-treatment measure of the patient-therapist relationship , the Helping Alliance Question naire , yielded significant correlations with outcomes ( mean r = .65 ) ; among the therapy techniques , " purity " provided significant correlations with outcomes ( mean r = .44 ) , both across therapists and within each therapist 's case load . The three therapist-related factors were moderately associated with each other SUMMARY When Oregon shifted to managed care for Medicaid-funded substance abuse treatment , st and ardized patient placement and discharge criteria were rapidly implemented statewide . This prospect i ve , naturalistic study examines the validity and impact of placement criteria with a sample of 240 adults presenting for treatment compared to a sample of 287 in Washington state , where implementation was phased in slowly . Baseline profile analysis suggested better differentiation between Level II and Level III clients for the Oregon sample and better implementation than with the Washington sample , presumably because Oregon clinicians received more training and had more experience with the criteria . A majority of the Oregon sample was placed in intensive outpatient programs , consistent with the recommended level of care . In this study , placement criteria showed good potential for changing treatment planning behavior , increasing individualization , and improving utilization of new levels of care This study compared inpatient , intensive outpatient , and st and ard outpatient treatment setting s for persons with alcoholism and tested a priori hypotheses about the interaction of setting with client alcohol involvement and social network support for drinking . Participants ( N = 192 ) were assigned r and omly in cohorts to 1 of the 3 setting s. The setting s did not differ in posttreatment primary drinking outcomes , although in patients had significantly fewer jail and residential treatment days combined than out patients . Clients high in alcohol involvement benefited more from inpatient than outpatient care ; the opposite was true at low alcohol involvement levels . Network drinking support did not moderate setting effects . Clients low in cognitive functioning also appeared to benefit more from inpatient than outpatient care . Improved outcomes might be achieved by matching degree of alcohol involvement and cognitive functioning to level of care This study examined several hypotheses for matching patients to 12-Step and cognitive-behavioral ( CB ) treatments in a multisite evaluation of VA inpatient substance abuse programs . A total of 804 male patients in five 12-Step programs , and 1069 male patients in five CB programs completed an intake , discharge , and 1-year follow-up question naire . The findings did not support the notion that certain patient characteristics would differentially predict better outcomes after 12-Step and CB treatment This conclusion held when the purest 12-Step and CB programs were used , and when patients who received the full dose of treatment ( i.e. , treatment completers ) were examined separately . Process analyses of the hypothesized mechanisms underlying the patient-treatment matching effects did not yield the expected links among patient characteristics , proximal outcomes , and 1-year outcomes . Our conclusion is that there is no advantage to matching men with substance abuse problems to 12-Step or CB treatments based on the patient attributes measured here The majority of people presenting for publicly-funded substance abuse treatment relapse and receive multiple episodes of care before achieving long-term recovery . This Early Re-Intervention experiment evaluates the impact of a Recovery Management Checkup ( RMC ) protocol that includes quarterly recovery management checkups ( assessment s , motivational interviewing , and linkage to treatment re-entry ) . Data are from 448 adults who were r and omly assigned to either RMC or an attention ( assessment only ) control group . Participants were 59 % female , 85 % African American , and 75 % aged 30 - 49 . Participants assigned to RMC were significantly more likely than those in the control group to return to treatment , to return to treatment sooner , and to spend more subsequent days in treatment ; they were significantly less likely to be in need of additional treatment at 24 months . This demonstrates the importance of post-discharge recovery management checkups as a means to improve the long-term outcomes of people with chronic substance use disorders |
2,375 | 20,824,842 | The quality of intervention studies intended to increase h and hygiene compliance remains disappointing .
Although multifaceted campaigns with social marketing or staff involvement appear to have an effect , there is insufficient evidence to draw a firm conclusion . | BACKGROUND Health care-associated infection is a major cause of morbidity and mortality .
H and hygiene is regarded as an effective preventive measure .
OBJECTIVES To up date the review done in 2007 , to assess the short and longer-term success of strategies to improve h and hygiene compliance and to determine whether a sustained increase in h and hygiene compliance can reduce rates of health care-associated infection . | In a pediatric intensive care unit we conducted a 1-year prospect i ve study of 454 patients to determine whether wearing a gown decreased the overall nosocomial infection rate , incidence of intravascular catheter colonization , breaks in h and washing technique , and traffic . The overall infection rate was 26 ( 13 % ) of 198 admissions during the gown-wearing periods v 23 ( 9 % ) of 256 admissions for the periods when gowns were not worn ( P less than .25 ) . Of 348 intravascular catheter tips cultured 16 ( 4.6 % ) were colonized during gown-wearing periods compared with 21 ( 6.3 % ) of 330 when no gowns were worn ( P less than .25 ) . Of 78 patient contacts 54 ( 69 % ) were followed by no h and washing during gown-wearing periods and 59 ( 70 % ) of 84 contacts were followed by no h and washing during periods when no gowns were worn . The mean occurrence of visits per patient per hour and total visits per hour differed between gown-wearing and no-gown-wearing periods by analysis of variance , P less than .01 and P less than .005 , respectively . Although traffic was decreased during periods of gown use , overgowns are an expensive , ineffective method of decreasing nosocomial infection rates , vascular catheter colonization rates , and breaks in h and washing technique OBJECTIVE To assess the efficacy of a multimodal , central ly coordinated , multisite h and hygiene culture-change program ( HHCCP ) for reducing rates of methicillin-resistant Staphylococcus aureus ( MRSA ) bacteraemia and disease in Victorian hospitals . DESIGN , PARTICIPANTS AND SETTING A pilot HHCCP was conducted over a 24-month period ( October 2004 to September 2006 ) in six Victorian health care institutions ( 4 urban , 2 rural ; total beds , 2379 ) . Subsequently , we assessed the efficacy of an identical program implemented throughout Victorian public hospitals over a 12-month period ( beginning between March 2006 and July 2006 ) . MAIN OUTCOME MEASURES Rates of h and hygiene ( HH ) compliance ; rates of MRSA disease ( patients with bacteraemia and number of clinical isolates per 100 patient discharges [ PD ] ) . RESULTS Mean HH compliance improved significantly at all pilot program sites , from 21 % ( 95 % CI , 20%-22 % ) at baseline to 48 % ( 95 % CI , 47%-49 % ) at 12 months and 47 % ( 95 % CI , 46%-48 % ; range , 31%-75 % ) at 24 months . Mean baseline rates for the number of patients with MRSA bacteraemia and the number of clinical MRSA isolates were 0.05/100 PD per month ( range , 0.00 - 0.13 ) and 1.39/100 PD per month ( range , 0.16 - 2.39 ) , respectively . These were significantly reduced after 24 months to 0.02/100 PD per month for bacteraemia ( P = 0.035 for trend ; 65 fewer patients with bacteraemia ) and 0.73/100 PD per month for MRSA isolates ( P = 0.003 ; 716 fewer isolates ) . Similar findings were noted 12 months after the statewide roll-out , with an increase in mean HH compliance ( from 20 % to 53 % ; P < 0.001 ) and reductions in the rates of MRSA isolates ( P = 0.043 ) and bacteraemias ( P = 0.09 ) . CONCLUSIONS Pilot and subsequent statewide implementation of a multimodal HHCCP was effective in significantly improving HH compliance and reducing rates of MRSA infection Abstract H and washing practice s are persistently suboptimal among healthcare professionals and are also stubbornly resistant to change . The purpose of this quasi-experimental intervention trial was to assess the impact of an intervention to change organizational culture on frequency of staff h and washing ( as measured by counting devices inserted into soap dispensers on four critical care units ) and nosocomial infections associated with methicillin-resistant Staphylococcus aureus ( MRSA ) and vancomycin-resistant enterococci ( VRE ) . All staff in one of two hospitals in the mid-Atlantic region received an intervention with multiple components design ed to change organizational culture ; the second hospital served as a comparison . Over a period of 8 months , 860 567 soap dispensings were recorded , with significant improvements in the study hospital after 6 months of follow-up . Rates of MRSA were not significantly different between the two hospitals , but rates of VRE were significantly reduced in the intervention hospital during implementation Background Limited data describe the sustained impact of h and hygiene programs ( HHPs ) implemented in teaching hospitals , where the burden of healthcare-associated infections ( HAIs ) is high . We use a quasi-experimental , before and after , study design with prospect i ve hospital-wide surveillance of HAIs to assess the cost effectiveness of HHPs . Methods and Findings A 4-year hospital-wide HHP , with particular emphasis on using an alcohol-based h and rub , was implemented in April 2004 at a 2,200-bed teaching hospital in Taiwan . Compliance was measured by direct observation and the use of h and rub products . Poisson regression analyses were employed to evaluate the densities and trends of HAIs during the preintervention ( January 1999 to March 2004 ) and intervention ( April 2004 to December 2007 ) periods . The economic impact was estimated based on a case-control study in Taiwan . We observed 8,420 opportunities for h and hygiene during the study period . Compliance improved from 43.3 % in April 2004 to 95.6 % in 2007 ( p<.001 ) , and was closely correlated with increased consumption of the alcohol-based h and rub ( r = 0.9399 ) . The disease severity score ( Charlson comorbidity index ) increased ( p = .002 ) during the intervention period . Nevertheless , we observed an 8.9 % decrease in HAIs and a decline in the occurrence of bloodstream , methicillin-resistant Staphylococcus aureus , extensively drug-resistant Acinetobacter baumannii , and intensive care unit infections . The intervention had no discernable impact on HAI rates in the hematology/oncology wards . The net benefit of the HHP was US$ 5,289,364 , and the benefit-cost ratio was 23.7 with a 3 % discount rate . Conclusions Implementation of a HHP reduces preventable HAIs and is cost effective OBJECTIVE To evaluate the effectiveness of a positive deviance strategy for the improvement of h and hygiene compliance in 2 adult step-down units . DESIGN A 9-month , controlled trial comparing the effect of positive deviance on compliance with h and hygiene . SETTING Two 20-bed step-down units at a tertiary care private hospital . METHODS The first phase of our study was a 3-month baseline period ( from April to June 2008 ) in which h and hygiene episodes were counted by use of electronic h and washing counters . From July to September 2008 ( ie , the second phase ) , a positive deviance strategy was implemented in the east unit ; the west unit was the control unit . During the period from October to December 2008 ( ie , the third phase ) , positive deviance was applied in both units . RESULTS During the first phase , there was no statistically significant difference between the 2 step-down units in the number of episodes of h and hygiene per 1,000 patient-days or in the incidence density of healthcare-associated infections ( HAIs ) per 1,000 patient-days . During the second phase , there were 62,000 h and hygiene episodes per 1,000 patient-days in the east unit and 33,570 h and hygiene episodes per 1,000 patient-days in the west unit ( P < .01 ) . The incidence density of HAIs per 1,000 patient-days was 6.5 in the east unit and 12.7 in the west unit ( p = .04 ) . During the third phase , there was no statistically significant difference in h and hygiene episodes per 1,000 patient-days ( P = .16 ) or in incidence density of HAIs per 1,000 patient-days . CONCLUSION A positive deviance strategy yielded a significant improvement in h and hygiene , which was associated with a decrease in the overall incidence of HAIs It is now well known that st and ard statistical procedures become invali date d when applied to cluster r and omized trials in which the unit of inference is the individual . A result ing consequence is that research ers conducting such trials are faced with a multitude of design choices , including selection of the primary unit of inference , the degree to which clusters should be matched or stratified by prognostic factors at baseline , and decisions related to cluster subsampling . Moreover , application of ethical principles developed for individually r and omized trials may also require modification . We discuss several topics related to these issues , with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided OBJECTIVES . H and hygiene promotion interventions rarely result in sustained improvement , and an assessment of their impact on individual infection risk has been lacking . We sought to measure the impact of h and hygiene promotion on health care worker compliance and health care – associated infection risk among neonates . METHODS . We conducted an intervention study with a 9-month follow-up among all of the health care workers at the neonatal unit of the Children 's Hospital , University of Geneva Hospitals , between March 2001 and February 2004 . A multifaceted h and hygiene education program was introduced with compliance assessed during successive observational surveys . Health care – associated infections were prospect ively monitored , and genotypic relatedness of bloodstream pathogens was assessed by pulsed-field gel electrophoresis . A comparison of observed h and hygiene compliance and infection rates before , during , and after the intervention was conducted . RESULTS . A total of 5325 opportunities for h and hygiene were observed . Overall compliance improved gradually from 42 % to 55 % across study phases . This trend remained significant after adjustment for possible confounders and paralleled the measured increase in h and -rub consumption ( from 66.6 to 89.2 L per 1000 patient-days ) . A 9-month follow-up survey showed sustained improvement in compliance ( 54 % ) , notably with direct patient contact ( 49 % at baseline vs 64 % at follow-up ) . Improved compliance was independently associated with infection risk reduction among very low birth weight neonates . Bacteremia caused by clonally related pathogens markedly decreased after the intervention . CONCLUSIONS . H and hygiene promotion , guided by health care workers ' perceptions , identification of the dynamics of bacterial contamination of health care workers ' h and s , and performance feedback , is effective in sustaining compliance improvement and is independently associated with infection risk reduction among high-risk neonates OBJECTIVES To assess h and washing frequency according to CDC recommendations ; and to test a simple intervention to increase h and washing compliance , design ed for the unique setting of the ED . METHODS A prospect i ve , observational , before- and -after study design with a convenience sampling technique was used to assess h and washing compliance in the ED of a 742-bed urban , university-affiliated medical center with 65,000 visits annually . Emergency physicians ( EPs ) , registered nurses ( RNs ) , and nurse practitioners ( NPs ) were informed that their patient encounters were being monitored , but the nature of the study was kept confidential . A single observer evaluated individual EPs , RNs , and NPs in one- , two- , or three-hour blocks , recording compliance with CDC h and washing recommendations . After two weeks , brightly colored signs with CDC recommendations for h and washing were posted at all sinks and a copy of a related publication on h and washing by medical personnel was distributed to all staff . H and washing behaviors were again observed . RESULTS A total of 252 situations requiring h and washing were observed , 132 pre-intervention and 120 post-intervention . Total h and washing , h and washing by each staff design ation , and h and washing in each CDC recommendation category -- except h and washing between contacts with different patients --all showed tendencies toward improvement , though none was significant ( p > 0.05 ) . Both the NPs and RNs demonstrated significantly higher adherence to recommended h and washing between patients after the intervention than did the EPs ( 85 % vs 71 % vs 31 % , p < 0.01 and p < 0.05 , respectively ) . CONCLUSION Despite a trend in improvement of compliance with CDC recommendations , h and washing among ED personnel remained unacceptably low Introduction Achieving a sustained improvement in h and -hygiene compliance is the WHO ’s first global patient safety challenge . There is no RCT evidence showing how to do this . Systematic review s suggest feedback is most effective and call for long term well design ed RCTs , applying behavioural theory to intervention design to optimise effectiveness . Methods Three year stepped wedge cluster RCT of a feedback intervention testing hypothesis that the intervention was more effective than routine practice in 16 English/Welsh Hospitals ( 16 Intensive Therapy Units [ ITU ] ; 44 Acute Care of the Elderly [ ACE ] wards ) routinely implementing a national cleanyourh and s campaign ) . Intervention-based on Goal & Control theories . Repeating 4 week cycle ( 20 mins/week ) of observation , feedback and personalised action planning , recorded on forms . Computer-generated stepwise entry of all hospitals to intervention . Hospitals aware only of own allocation . Primary outcome : direct blinded h and hygiene compliance ( % ) . Results All 16 trusts ( 60 wards ) r and omised , 33 wards implemented intervention ( 11 ITU , 22 ACE ) . Mixed effects regression analysis ( all wards ) accounting for confounders , temporal trends , ward type and fidelity to intervention ( forms/month used ) . Intention to Treat Analysis Estimated odds ratio ( OR ) for h and hygiene compliance rose post r and omisation ( 1.44 ; 95 % CI 1.18 , 1.76;p<0.001 ) in ITUs but not ACE wards , equivalent to 7–9 % absolute increase in compliance . Per- Protocol Analysis for Implementing Wards OR for compliance rose for both ACE ( 1.67 [ 1.28–2.22 ] ; p<0.001 ) & ITUs ( 2.09 [1.55–2.81];p<0.001 ) equating to absolute increases of 10–13 % and 13–18 % respectively . Fidelity to intervention closely related to compliance on ITUs ( OR 1.12 [ 1.04 , 1.20];p = 0.003 per completed form ) but not ACE wards . Conclusion Despite difficulties in implementation , intention-to-treat , per- protocol and fidelity to intervention , analyses showed an intervention coupling feedback to personalised action planning produced moderate but significant sustained improvements in h and -hygiene compliance , in wards implementing a national h and -hygiene campaign . Further implementation studies are needed to maximise the intervention ’s effect in different setting s. Trial Registration Controlled-Trials.com IS RCT In this prospect i ve cluster r and omized controlled trial we evaluated the impact of short-term provision of enhanced infection control support on infection control practice in nursing homes in South London . Twelve nursing homes were recruited , six each in intervention ( 300 residents ) and control ( 265 residents ) groups . Baseline observations of h and hygiene facilities , environmental cleanliness and safe disposal of clinical waste showed poor compliance in both groups . Post-intervention observations showed improvement in both groups . There was no statistical difference between the two groups in the compliance for h and hygiene facilities ( P=0.69 ) ; environmental cleanliness ( P=0.43 ) and safe disposal of clinical waste ( P=0.96 ) . In both groups , greatest improvement was in compliance with safe disposal of clinical waste and the least improvement was in h and hygiene facilities . Since infection control practice improved in intervention and control groups , we could not demonstrate that provision of short-term , enhanced , infection control support in nursing homes had a significant impact in infection control practice Introduction H and hygiene is one of the cornerstones of the prevention of health care-associated infection , but health care worker ( HCW ) compliance with good practice s remains low . Alcohol-based h and rub is the new st and ard for h and hygiene action worldwide and usually requires a system change for its successful introduction in routine care . Product acceptability by HCWs is a crucial step in this process . Methods We conducted a prospect i ve intervention study to compare the impact on HCW compliance of a liquid ( study phase I ) versus a gel ( phase II ) h and rub formulation of the same product during daily patient care . All staff ( 102 HCWs ) of the medical intensive care unit participated . Compliance with h and hygiene was monitored by a single observer . Skin tolerance and product acceptability were assessed using subjective and objective scoring systems , self-report question naires , and biometric measurements . Logistic regression was used to estimate the association between predictors and compliance with the h and rub formulation as the main explanatory variable and to adjust for potential risk factors . Results Overall compliance ( phases I and II ) with h and hygiene practice s among nurses , physicians , nursing assistants , and other HCWs was 39.1 % , 27.1 % , 31.1 % , and 13.9 % , respectively ( p = 0.027 ) . Easy access to h and rub improved compliance ( 35.3 % versus 50.6 % , p = 0.035 ) . Nurse status , working on morning shifts , use of the gel formulation , and availability of the alcohol-based h and rub in the HCW 's pocket were independently associated with higher compliance . Immediate accessibility was the strongest predictor . Based on self- assessment , observer assessment , and the measurement of epidermal water content , the gel performed significantly better than the liquid formulation . Conclusion Facilitated access to an alcohol-based gel formulation leads to improved compliance with h and hygiene and better skin condition in HCWs A national effort to reduce nosocomial infections includes a program developed at the National Institutes of Health to encourage h and washing in hospitals and day care centers . The program promotes a symbolic teddy bear ( T. Bear ) with slogans to remind hospital personnel and patients to practice h and washing . One of the items used is a stuffed toy T. Bear to be dispensed to the hospitalized child . Considering the manner in which children h and le stuffed toys , we suspected the T. Bear might serve as a " fomite " for transmission of nosocomial microbes . A prospect i ve study of 39 sterilized T. Bears revealed that all became colonized with bacteria , fungi , or both within 1 week of hospitalization . Hospital acquired organisms cultured from the T. Bear included Staphylococcus epidermidis , Staphylococcus aureus , alpha streptococci , Corynebacterium acnes , Micrococcus sp , Klebsiella pneumoniae , Pseudomonas aeruginosa , Escherichia coli , Bacillus sp , and species of C and ida , Cryptococcus , Trichosporon , Aspergillus and others . Concomitant cultures of the patients revealed similar isolates . Although the T. Bear h and washing campaign should not be discredited , the promotional toy may pose an unnecessary expense and hazard and should not be used in hospitals or day care centers BACKGROUND H and hygiene prevents cross infection in hospitals , but compliance with recommended instructions is commonly poor . We attempted to promote h and hygiene by implementing a hospital-wide programme , with special emphasis on bedside , alcohol-based h and disinfection . We measured nosocomial infections in parallel . METHODS We monitored the overall compliance with h and hygiene during routine patient care in a teaching hospital in Geneva , Switzerl and , before and during implementation of a h and -hygiene campaign . Seven hospital-wide observational surveys were done twice yearly from December , 1994 , to December , 1997 . Secondary outcome measures were nosocomial infection rates , attack rates of methicillin-resistant Staphylococcus aureus ( MRSA ) , and consumption of h and rub disinfectant . FINDINGS We observed more than 20,000 opportunities for h and hygiene . Compliance improved progressively from 48 % in 1994 , to 66 % in 1997 ( p<0.001 ) . Although recourse to h and washing with soap and water remained stable , frequency of h and disinfection substantially increased during the study period ( p<0.001 ) . This result was unchanged after adjustment for known risk factors of poor adherence . H and hygiene improved significantly among nurses and nursing assistants , but remained poor among doctors . During the same period , overall nosocomial infection decreased ( prevalence of 16.9 % in 1994 to 9.9 % in 1998 ; p=0.04 ) , MRSA transmission rates decreased ( 2.16 to 0.93 episodes per 10,000 patient-days ; p<0.001 ) , and the consumption of alcohol-based h and rub solution increased from 3.5 to 15.4 L per 1000 patient-days between 1993 and 1998 ( p<0.001 ) . INTERPRETATION The campaign produced a sustained improvement in compliance with h and hygiene , coinciding with a reduction of nosocomial infections and MRSA transmission . The promotion of bedside , antiseptic h and rubs largely contributed to the increase in compliance We tested the effectiveness of specific vs. general infection control interventions in a teaching hospital in Guatemala City . After 3 months of prospect i ve surveillance , we implemented targeted interventions ( i.e. , modification of respiratory tract care and use of a closed urinary catheter drainage system ) , an educational program focused on respiratory intervention , and general interventions ( i.e. , aseptic technique ) . The rate of nosocomial pneumonia , the most common nosocomial infection , decreased from 33 % ( 41 of 123 patients ) before intervention to 16 % ( 21 of 130 patients ) after intervention ( P = .001 ) . Although the frequency of h and washing increased from 5 % to 63 % ( P < .001 ) , the rates of other types of nosocomial infections did not change significantly . The combination of targeted respiratory intervention and an intense , focused educational campaign reduced the rate of nosocomial pneumonia . General improvements in hygiene and h and washing rates , or even implementation of a closed urinary drainage system without focused education , may not be sufficient to reduce infection rates in intensive care units in developing countries Objective : Proper h and hygiene ( HH ) reduces nosocomial infections . Therefore , factors that influence HH behavior of healthcare workers are of great interest . We hypothesized that strict HH adherence by supervisor role models would improve the HH behavior of junior staff . Design : Prospect i ve observational study . Setting : Pediatric and cardiac intensive care units of a tertiary care children ’s hospital . Subjects : Two critical care fellows and four nurse orientees . Interventions : First , we observed and recorded HH adherence of the fellows and nurse orientees and their respective supervising attending physician or nurse preceptor during daily patient care . Subsequently , we paired the same fellows and nurse orientees with a different supervisor who maintained strict HH adherence , and again noted HH adherence . We used measures of HH opportunities and HH adherence consistent with guidelines set by the Centers for Disease Control and Prevention and Association for Professionals in Infection Control and Epidemiology . Measurements and Main Results : HH adherence by fellows and nurse orientees at baseline was 22 % of 200 HH opportunities , and improved to 56 % of 234 opportunities as a result of role modeling — an average increase of 34 % points ( 95 % confidence interval , 18.7–51 ; p < 0.01 by linear regression ) , representing a HH adherence rate greater than 1.5 times that of the baseline . The control senior practitioners ’ HH adherence rate was 20 % of 180 opportunities compared with the study senior practitioners ’ HH adherence of 94 % of 187 opportunities — an average difference of 72 % points higher compared with the control senior practitioners ( 95 % confidence interval , 56–88.3 ; p < 0.01 by linear regression ) . Conclusions : HH adherence of junior practitioners improved under the supervision of adherent role models . These results suggest that HH behavior of senior practitioners plays a crucial influence on other staff . Senior healthcare practitioners should consider the important role they may play in reinforcing or weakening a culture of patient safety and proper HH OBJECTIVE To evaluate the effectiveness of a multimodal intervention in primary care health professionals for improved compliance with h and hygiene practice , based on the World Health Organization 's 5 Moments for Health Hygiene . DESIGN Cluster r and omized trial , parallel 2-group study ( intervention and control ) . SETTING Primary healthcare centers in Madrid , Spain . PARTICIPANTS Eleven healthcare centers with 198 healthcare workers ( general practitioners , nurses , pediatricians , auxiliary nurses , midwives , odontostomatologists , and dental hygienists ) . Methods . The multimodal h and hygiene improvement strategy consisted of training of healthcare workers by teaching sessions , implementation of hydroalcoholic solutions , and installation of reminder posters . The h and hygiene compliance level was evaluated by observation during regular care activities in the office visit setting , at the baseline moment , and 6 months after the intervention , all by a single external observer . RESULTS The overall baseline compliance level was 8.1 % ( 95 % confidence interval [ CI ] , 6.2 - 10.1 ) , and the healthcare workers of the intervention group increased their h and hygiene compliance level by 21.6 % ( 95 % CI , 13.83 - 28.48 ) compared with the control group . CONCLUSIONS This study has demonstrated that h and hygiene compliance in primary healthcare workers can be improved with a multimodal h and hygiene improvement strategy OBJECTIVE To determine whether a multimodal intervention could improve adherence to h and hygiene and glove use recommendations and decrease the incidence of antimicrobial resistance in different types of healthcare facilities . DESIGN Prospect i ve , observational study performed from October 1 , 1999 , through December 31 , 2002 . We monitored adherence to h and hygiene and glove use recommendations and the incidence of antimicrobial-resistant bacteria among isolates from clinical cultures . We evaluated trends in and predictors for adherence and preferential use of alcohol-based h and rubs , using multivariable analyses . SETTING Three intervention hospitals ( a 660-bed acute and long-term care hospital , a 120-bed community hospital , and a 600-bed public teaching hospital ) and a control hospital ( a 700-bed university teaching hospital).Intervention . At the intervention hospitals , we introduced or increased the availability of alcohol-based h and rub , initiated an interactive education program , and developed a poster campaign ; at the control hospital , we only increased the availability of alcohol-based h and rub . RESULTS We observed 6,948 h and hygiene opportunities . The frequency of h and hygiene performance or glove use significantly increased during the study period at the intervention hospitals but not at the control hospital ; the maximum quarterly frequency of h and hygiene performance or glove use at intervention hospitals ( 74 % , 80 % , and 77 % ) was higher than that at the control hospital ( 59 % ) . By multivariable analysis , preferential use of alcohol-based h and rubs rather than soap and water for h and hygiene was more likely among workers at intervention hospitals compared with nonintervention hospitals ( adjusted odds ratio , 4.6 [ 95 % confidence interval , 3.3 - 6.4 ] ) and more likely among physicians ( adjusted odds ratio , 1.4 [ 95 % confidence interval , 1.2 - 1.8 ] ) than among nurses at intervention hospitals . A significantly reduced incidence of antimicrobial-resistant bacteria among isolates from clinical culture was found at a single intervention hospital , which had the greatest increase in the frequency of h and hygiene performance . CONCLUSIONS During a 3-year period , a multimodal intervention program increased adherence to h and hygiene recommendations , especially to the use of alcohol-based h and rubs . In one hospital , a concomitant reduction was found in the incidence of antimicrobial-resistant bacteria among isolates from clinical cultures Problem Bloodstream infections associated with catheters were the most common nosocomial infections in one paediatric intensive care unit in 1994 - 7 , with rates well above the national average . Design Clinical data were collected prospect ively to assess the rates of infection from 1994 onwards . The high rates in 1994 - 7 led to the stepwise introduction of interventions over a five year period . At quarterly intervals , prospect i ve data continued to be collected during this period and an additional three year follow-up period . Setting A 292 bed tertiary care children 's hospital . Key measures for improvement We aim ed to reduce our infection rates to below the national mean rates for similar units by 2000 ( a 25 % reduction ) . Strategies for change A stepwise introduction of interventions design ed to reduce infection rates , including maximal barrier pre caution s , transition to antibiotic impregnated central venous catheters , annual h and washing campaigns , and changing the skin disinfectant from povidone-iodine to chlorhexidine . Effects of change Significant decreases in rates of infection occurred over the intervention period . These were sustained over the three year follow-up . Annual rates decreased from 9.7/1000 days with a central venous catheter in 1997 to 3.0/1000 days in 2005 , which translates to a relative risk reduction of 75 % ( 95 % confidence interval 35 % to 126 % ) , an absolute risk reduction of 6 % ( 2 % to 10 % ) , and a number needed to treat of 16 ( 10 to 35 ) . Lessons learnt A stepwise introduction of interventions leading to a greater than threefold reduction in nosocomial infections can be implemented successfully . This requires a multidisciplinary team , support from hospital leadership , ongoing data collection , shared data interpretation , and introduction of evidence based interventions BACKGROUND Barrier pre caution s ( gowns and gloves ) prevent horizontal transmission of pathogens . Nosocomial infections have been linked to poor h and hygiene . Isolation rooms for infection control improve h and hygiene and decrease nosocomial infections . We hypothesized that both patient isolation and electronic h and hygiene prompts incrementally improve h and hygiene of health care workers compared with nonisolation rooms . METHODS A prospect i ve , 14.5-month , 3-phase electronic surveillance study of h and hygiene behavior on an intermediate care unit with 9 patient rooms ( 3 isolation rooms , 6 nonisolation rooms ) was conducted . ( phase I : electronic observation , phase II : electronic observation with automated voice messages urging h and hygiene , phase III : electronic observation ) . Electronic sensors monitored room entries and exits and use of all sinks and all soap dispensers . Phases compared by 2 x 3 Tables , and odds ratios ( OR ) and 95 % confidence intervals ( CI ) are reported . RESULTS Phase I ( 1616 patient-days ) health care workers were 49 % more likely to wash their h and s in isolation rooms versus nonisolation rooms ( OR , 1.49 ; 95 % CI : 1.17 - 1.88 ) . Phase II ( 1390 patient-days ) and phase III ( 543 patient-days ) health care workers were 59 % more likely to wash their h and s in isolation versus nonisolation rooms ( OR , 1.59 ; 95 % CI : 1.17 - 2.14 ) , P = .001 . CONCLUSION Health care workers improve h and hygiene when constrained by isolation rooms . Electronic voice prompts further improve h and hygiene behavior . Both physical and auditory reminders improve h and hygiene OBJECTIVE To evaluate the effects of a h and hygiene program on compliance with h and hygiene and the rate of nosocomial infections in a neonatal intensive care unit ( NICU ) . DESIGN Open trial . SETTING A level-III NICU in a teaching hospital . PARTICIPANTS Nurses , physicians , and other healthcare workers in the NICU . INTERVENTIONS A multimodal campaign for h and hygiene promotion was conducted beginning in September 1998 . This program consisted of formal lectures , written instructions and posted reminders regarding h and hygiene and proper h and washing techniques , covert observation , financial incentives , and regular group feedback on compliance . Surveillance of h and washing compliance and nosocomial infections before and during the program was analyzed . RESULTS Overall compliance with h and hygiene improved from 43 % at baseline to 80 % during the promotion program . The rate of nosocomial infections decreased from 15.13 to 10.69 per 1,000 patient-days ( P = .003 ) with improved h and washing compliance . In particular , respiratory tract infections decreased from 3.35 to 1.06 per 1,000 patient-days during the h and washing campaign ( P = .002 ) . Furthermore , the correlation between nosocomial infection of the respiratory tract and h and washing compliance also reached statistical significance ( r = -0.385 ; P = .014 ) . CONCLUSIONS Improved compliance with h and washing was associated with a significant decrease in overall rates of nosocomial infection and respiratory infections in particular . Washing h and s is a simple , economical , and effective method for preventing nosocomial infections in the NICU Objectives : To study the impact of a teaching intervention on the rate of central venous catheter-related bloodstream infections ( CRBSI ) in intensive care patients . Design : Prospect i ve before/after interventional cohort study on medical and surgical intensive care units . Setting : University hospital with five adult intensive care units . Patients : All patients with a central venous catheter on the five ICUs from September to December 2003 ( baseline period ) and from March to July 2004 ( intervention period ) . Interventions : Educational program with teaching of h and hygiene , st and ards of catheter care , and preparation of intravenous drugs . Measurements and Main Results : The primary outcome variable was the rate of CRBSIs per 1000 catheter days during a baseline period of 4 months and an intervention period of 5 months . The secondary outcome variable was compliance with h and hygiene . Of the patients , 499 patients with 6200 catheter days in the baseline period and 500 patients with 7279 catheter days were monitored in the intervention period . The incidence density of CRBSI decreased from 3.9 per 1000 catheter days in the preintervention phase to 1.0 per 1000 catheter days in the intervention phase ( p < 0.001 ) . The risk for CRBSI was significantly higher in the baseline period in both univariate and multivariate analysis . Other independent risk factors were hospitalization in the medical ICU and male gender . Time to CRBSI was significantly longer in the intervention period ( median 9 days vs. 6.5 days , respectively ; p = 0.02 ) . Compliance with h and hygiene improved slightly from 59 % in the baseline period to 65 % in the intervention period , but the rate of correct performance of the practice increased from 22.5 % to 42.6 % ( p = 0.003 ) . Conclusions : Evidence -based catheter-care procedures , guided by healthcare workers ' perceptions and including bedside teaching , reduce significantly the CRBSI rate and demonstrate that improving catheter care has a major impact on its prevention BACKGROUND H and washing ( HW ) by clinical staff is the single most important measure for preventing transmission of nosocomial infection ( NI ) . The primary objectives of this study were to improve the motivation and awareness of the importance of HW practice s among health care workers ( HCWs ) and to assess the effectiveness of a new chemical system in checking HW compliance . In addition , we evaluated the efficacy and tolerability of 2 soap solutions used during regular working hours by HCWs at our institution . METHOD A preliminary short training course was performed to promote HW compliance and awareness . We chose 2 surgical wards at our 1200-bed teaching hospital . Sampling of h and s was conducted weekly during routine activities of HCWs without advance warning . We used the staff list as a sampling frame to select subjects . Data were collected anonymously . On the basis of a crossover study design , a plain soap and one containing 4 % chlorhexidine gluconate ( CHG ) were used alternatively in each ward for 4 consecutive months . H and sample s were evaluated with microbiologic cultures and with a commercially available kit that measures adenosine triphosphate ( ATP ) bioluminescence . As additional process indicators , we examined the amount of h and soap and CHG solution distributed and rate of NIs . RESULTS A total of 74 HCWs were evaluated for h and contamination . During the 4-month study , we found a significant reduction in colony-forming unit counts ( P < .008 ) and ATP levels ( P < .002 ) compared with baseline values . The results showed a positive correlation ( r = 0.68 , P < .0001 ) between the microbial counts detected by st and ard culture and ATP levels measured with the commercial kit . Plain soap ( P < .003 ) was more effective than CHG in reducing colony-forming unit counts among HCWs in the vascular surgery ward . We documented a reduction in the NI rate and an increase in the consumption of soap and paper towels . CONCLUSION HW compliance improved during the study period among HCWs . The method to measure ATP bioluminescence is simple and easy to perform and provides reliable results within a few minutes of sampling h and s. It can be used extensively to test HW compliance among HCWs OBJECTIVE To evaluate h and hygiene compliance in 2 adult step-down units ( SDUs ) . DESIGN A 6-month ( from March to September 2007 ) , controlled trial comparing 2 SDUs , one with a feedback intervention program ( ie , the intervention unit ) and one without ( ie , the control unit ) . SETTING Two 20-bed SDUs at a tertiary care private hospital . METHODS H and hygiene episodes were measured by electronic recording devices and periodic observational surveys . In the intervention unit , feedback was provided by the SDU nurse manager , who explained twice a week to the healthcare workers the goals and targets for the process measures . RESULTS A total of 117,579 h and hygiene episodes were recorded in the intervention unit , and a total of 110,718 were recorded in the control unit ( P = .63 ) . There was no significant difference in the amount of chlorhexidine used in the intervention and control units ( 34.0 vs 26.7 L per 1,000 patient-days ; P = .36 ) or the amount of alcohol gel used ( 72.5 vs 70.7 L per 1,000 patient-days ; P = .93 ) . However , in both units , healthcare workers used alcohol gel more frequently than chlorhexidine ( 143.2 vs 60.7 L per 1,000 patient-days ; P < .001 ) . Nosocomial infection rates in the intervention and control units , respectively , were as follows : for bloodstream infection , 3.5 and 0.79 infections per 1,000 catheter-days ( P = .18 ) ; for urinary tract infection , 15.8 and 15.7 infections per 1,000 catheter-days ( P = .99 ) ; and for tracheostomy-associated pneumonia , 10.7 and 5.1 infections per 1,000 device-days ( P = .13 ) . There were no cases of infection with vancomycin-resistant enterococci and only a single case of infection with methicillin-resistant Staphylococcus aureus ( in the control unit ) . CONCLUSIONS The feedback intervention regarding h and hygiene had no significant effect on the rate of compliance . Other measures must be used to increase and sustain the rate of h and hygiene compliance BACKGROUND A review of the literature on h and washing has documented the absence of research on the education of the patient as an intervention model for changing staff behavior regarding h and washing compliance . The primary objective of this project was to conduct a prospect i ve control study of the effect of patient h and washing education on staff compliance with h and washing . METHOD A prospect i ve , controlled , 6-week intervention/control study was performed in 4 community hospitals in South Jersey . Each hospital served as its own control . Patients were educated within 24 hours of admission about the importance of asking their health care workers to wash their h and s. Soap usage and h and washing was calculated by bed-days . Patient follow-up was conducted through telephone interviews 2 weeks after discharge . RESULTS The patient h and washing education model increased soap usage by health care workers an average of 34 % ( P = .021 ) ; this increase was consistent across hospitals regardless of the initial soap usage rates . Of the patients interviewed , 81 % read the material s provided , 57 % asked health care workers whether they had washed their h and s , and 81 % of this 57 % said they received positive responses . CONCLUSIONS For the first time , our findings document that education of patients regarding their role in monitoring h and washing compliance among health care workers can increase soap usage and h and washing and provide sustainable reinforcement of h and washing principles for health care workers BACKGROUND There are limited data from prospect i ve studies to indicate whether improvement in h and hygiene associated with the use of alcohol-based h and hygiene products results in improved patient outcomes . DESIGN A 2-year , prospect i ve , controlled , cross-over trial of alcohol-based h and gel . SETTING The study was conducted in 2 medical-surgical ICUs for adults , each with 12 beds , from August 2001 to September 2003 at a university-associated , tertiary care teaching hospital . METHODS An alcohol-based h and gel was provided in one critical care unit and not provided in the other . After 1 year , the assignment was reversed . The h and hygiene adherence rate and the incidence of nosocomial infection were monitored . Sample s for culture were obtained from nurses ' h and s every 2 months . RESULTS During 17,994 minutes of observation , which included 3,678 opportunities for h and hygiene , adherence rates improved dramatically after the introduction of h and gel , increasing from 37 % to 68 % in one unit and from 38 % to 69 % in the other unit ( P < .001 ) . Improvement was observed among all groups of healthcare workers . H and hygiene rates were better at higher workloads when h and gel was available in the unit ( P= .02 ) . No substantial change in the rates of device-associated infection , infection due to multidrug-resistant pathogens , or infection due to Clostridium difficile was observed . Culture of sample s from the h and s of nursing staff revealed that an increased number of microbes and an increased number of microbe species was associated with longer fingernails ( ie , more than 2 mm long ) , the wearing of rings , and /or lack of access to h and gel . CONCLUSIONS The introduction of alcohol-based gel result ed in a significant and sustained improvement in the rate of h and hygiene adherence . Fingernail length greater than 2 mm , wearing rings , and lack of access to h and gel were associated with increased microbial carriage on the h and s. This improvement in the h and hygiene adherence rate was not associated with detectable changes in the incidence of healthcare-associated infection OBJECTIVE To investigate the effectiveness of a multifaceted h and hygiene program involving the use of pocket-sized containers of antiseptic gel in long-term care facilities ( LTCFs ) with elderly residents . METHODS In this clustered r and omized controlled trial , Hong Kong LTCFs for elderly persons were recruited via snowball sampling . Staff h and hygiene adherence was directly observed , and residents ' infections necessitating hospitalization were recorded . After a 3-month preintervention period , LTCFs were r and omized to receive pocket-sized containers of alcohol-based gel , reminder material s , and education for all HCWs ( treatment group ) or to receive basic life support education and workshops for all healthcare workers ( HCWs ) ( control group ) . A 2-week intervention period ( April 1 - 15 , 2007 ) was followed by 7 months of postintervention observations . RESULTS In the 3 treatment LTCFs , adherence to h and rubbing increased from 5 ( 1.5 % ) of 333 to 233 ( 15.9 % ) of 1,465 h and hygiene opportunities ( P = .001 ) and total h and hygiene adherence increased from 86 ( 25.8 % ) of 333 to 488 ( 33.3 % ) of 1,465 opportunities ( P = .01)after intervention ; the 3 control LTCFs showed no significant change . In the treatment group , the incidence of serious infections decreased from 31 cases in 21,862 resident-days ( 1.42 cases per 1,000 resident-days ) to 33 cases in 50,441 resident-days ( 0.65 cases per 1,000 resident-days ) ( P = .002 ) , whereas in the control group , it increased from 16 cases in 32,726 resident-days ( 0.49 cases per 1,000 resident-days ) to 85 cases in 81,177 resident-days ( 1.05 cases per 1,000 resident-days ) ( P = .004 ] ) . In the treatment group , the incidence of pneumonia decreased from 0.91 to 0.28 cases per 1,000 resident-days ( P = .001 ) and the death rate due to infection decreased from 0.37 to 0.10 deaths per 1,000 resident-days ( P = .01 ) ; the control group revealed no significant change . CONCLUSIONS A h and hygiene program involving the use of pocket-sized containers of antiseptic gel and education could effectively increase adherence to h and rubbing and reduce the incidence of serious infections in LTCFs with elderly residents BACKGROUND H and hygiene is an effective strategy for the prevention of health care-associated infection ( HAI ) . We investigated the effect of a h and hygiene promotion strategy introducing alcohol-based h and rub ( AHBR ) on the incidence of HAI in a university hospital in Colombia . METHODS A Prospect i ve cohort study was performed in 6 intensive care units from January 2001 to December 2005 . HAI were identified using st and ard US Centers for Disease Control and Prevention definitions . Alcohol-based h and rub dispensers were installed between February and June 2002 . RESULTS Total ABHR consumption was 5,794 L ( mean , 28.9 L per 1,000 patient-days ) and significantly increased over time ( + 9.2 % per year ; P < .001 ) . Of 14,516 patients cumulating 166,498 patient-days , 2,398 ( 16.5 % ) acquired a total of 3,490 HAI episodes ( 20.9 per 1,000 patient-days ) . Incidence densities for central line-associated bloodstream infection ( CLABSI ) , ventilator-associated pneumonia , and urinary tract infections were 7.7 , 10.6 , and 3.6 episodes per 1,000 device-days , respectively . A significant decrease was observed for CLABSI ( -12.7 % per year ; P < .001 ) with low nurse-to-patient ratio independently associated with infection ( odds ratio , 1.11 ; 95 % confidence interval : 1.07 - 1.16 ; P < .001 ) . CONCLUSION Improved h and hygiene measured by increased ABHR consumption result ed in CLABSI reduction . Low nurse-to-patient ratio is independently associated with HAI in an upper-middle income country OBJECTIVE To investigate the potential reservoir and mode of transmission of p and rug-resistant ( PDR ) Acinetobacter baumannii in a 7-day-old neonate who developed PDR A. baumannii bacteremia that was presumed to be the iceberg of a potential outbreak . DESIGN Outbreak investigation based on a program of prospect i ve hospital-wide surveillance for nosocomial infection . SETTING A 24-bed neonatal intensive care unit in a 2,200-bed major teaching hospital in Taiwan that provides care for critically ill neonates born in this hospital and those transferred from other hospitals . INTERVENTIONS Sample s from 33 healthcare workers ' h and s and 40 sample s from the environment were cultured . Surveillance cultures of anal swab specimens and sputum sample s were performed for neonates on admission to the neonatal intensive care unit and every 2 weeks until discharge . The PDR A. baumannii isolates , defined as isolates resistant to all currently available systemic antimicrobials except polymyxin B , were analyzed by pulsed-field gel electrophoresis . Control measures consisted of implementing contact isolation , reinforcing h and hygiene adherence , cohorting of nurses , and environmental cleaning . RESULTS One culture of an environmental sample and no cultures of sample s from healthcare workers ' h and s grew PDR A. baumannii . The positive culture result involved a sample obtained from a ventilation tube used by the index patient . During the following 2 months , active surveillance identified PDR A. baumannii in 8 additional neonates , and isolates from 7 had the same electrokaryotype . Of the 9 neonates colonized or infected with PDR A. baumannii , 1 died from an unrelated condition . Reinforcement of infection control measures result ed in 100 % adherence to proper h and hygiene protocol . The outbreak was stopped without compromising patient care . CONCLUSIONS In the absence of environmental contamination , transient h and carriage by personnel who cared for neonates colonized or infected with PDR A. baumannii was suspected to be the mode of transmission . Vigilance , prompt intervention and strict adherence to h and hygiene protocol were the key factors that led to the successful control of this outbreak . Active surveillance appears to be an effective measure to identify potential transmitters and reservoirs of PDR A. baumannii & NA ; Using a pre‐ and posttest design with no control group , the authors evaluated the impact of a peer‐group intervention on work related knowledge and behavior for health workers at an urban hospital in Malawi . The authors surveyed unmatched r and om sample s of health workers , observed workers on the job , and interviewed clients about hospital services at baseline and at 6 months after the intervention . Universal pre caution s knowledge , reported h and washing , and reported client teaching were significantly higher at the final evaluation . The outcome differences remained robust in multivariate analyses with controls for demographic factors of age , gender , education , food security , and job category . Observations reported consistently greater use of universal pre caution s , more respectful interactions , and more client teaching at final evaluation . Patient surveys reported more discussion with health workers about HIV at the final evaluation . Peer‐group interventions can prepare health workers in Malawi for HIV prevention and offer a potential model for other African countries BACKGROUND H and hygiene ( HH ) is critical to infection control , but compliance is low . Alcohol-based antiseptics may improve HH . HH practice s in Russia are not well described , and facilities are often inadequate . SETTING Four 6-bed units in a neonatal intensive care unit in St. Petersburg , Russia . METHODS Prospect i ve surveillance of HH compliance , nosocomial colonization , and antibiotic administration was performed from January until June 2000 . In February 2000 , alcohol-based h and rub was provided for routine HH use . Eight weeks later , a quality improvement intervention was implemented , consisting of review of interim data , identification of opinion leaders , posting of colonization incidence rates , and regular feedback . Means of compliance , colonization , and antibiotic use were compared for periods before and after each intervention . RESULTS A total of 1,027 events requiring HH were observed . Compliance was 44.2 % before the first intervention , 42.3 % between interventions , and 48 % after the second intervention . Use of alcohol rose from 15.2 % of HH indications to 25.2 % between interventions and 41.5 % after the second intervention . The incidence of nosocomial colonization ( per 1,000 patient-days ) with Klebsiella pneumoniae was initially 21.5 , decreased to 4.7 , and then was 3.2 in the final period . Rates of antibiotic and device use also decreased . CONCLUSIONS HH may have increased slightly , but the largest effect was a switch from soap and water to alcohol which may have been associated with decreased cross-transmission of Klebsiella , although this may have been confounded by lower device use . Alcohol-based antiseptic may be an improvement over current practice s , but further research is required OBJECTIVES Adherence to h and hygiene among healthcare workers ( HCWs ) is widely believed to be a key factor in reducing the spread of healthcare-associated infection . The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to h and hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus ( MRSA ) colonization . DESIGN Cluster-r and omized controlled trial . SETTING Thirty hospital units in 3 tertiary care hospitals in Hamilton , Ontario , Canada . INTERVENTION After a 3-month baseline period of data collection , 15 units were r and omly assigned to the intervention arm ( with performance feedback , small-group teaching seminars , and posters ) and 15 units to usual practice . H and hygiene was observed during r and omly selected 15-minute periods on each unit , and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008 . RESULTS We found that 3,812 ( 48.2 % ) of 7,901 opportunities for h and hygiene in the intervention group result ed in adherence , compared with 3,205 ( 42.6 % ) of 7,526 opportunities in the control group ( P < .001 ; independent t test ) . There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group . CONCLUSION Among HCWs in Ontario tertiary care hospitals , the rate of adherence to h and hygiene had a statistically significant increase of 6 % with a multifaceted intervention , but the incidence of MRSA colonization was not reduced BACKGROUND Few interventions to influence h and washing have had measurable effects . This prospect i ve quasi-experimental study was design ed to address predisposing , enabling , and reinforcing factors to improve frequency of h and washing . METHODS Over a 12-month time period , a multifaceted intervention including focus group sessions , installation of automated sinks , and feedback to staff on h and washing frequency was implemented in one intensive care unit ; a second unit served as a control . Dependent variables observed were h and washing frequency and self-reported practice s and opinions about h and washing . Study phases included baseline , three phases of about 2 months each in duration in which sink automation was incrementally increased , and follow-up 2 months after intervention . RESULTS During 301 hours of observation , 2624 h and washings were recorded . Proportion of times h and s were washed varied by indication , ranging from 38 % before invasive procedures to 86 % for dirty-to-clean procedures ( p < 0.00001 ) . Although there were some significant differences between experimental and control units in h and washing during the study , these differences had returned to baseline by the 2-month follow-up . There were no significant differences in self-reported practice s and opinions from before to after intervention nor between units . CONCLUSIONS Intensive intervention , including feedback , education , and increased sink automation , had minimal long-term effect on h and washing frequency OBJECTIVE To determine whether h and washing would increase with sustained feedback based on measurements of soap and paper towel consumption . DESIGN Prospect i ve trial with a nonequivalent control group . SETTING Open multibed rooms in the Omaha Veterans Affairs Medical Center 's Surgical Intensive Care Unit ( SICU ) and Medical Intensive Care Unit ( MICU ) . SUBJECTS Unit staff . INTERVENTION Every weekday from May 26 through December 8 , 1998 , we recorded daytime soap and paper towel consumption , nurse staffing , and occupied beds in the SICU ( intervention unit ) and the MICU ( control unit ) and used these data to calculate estimated h and washing episodes ( EHWEs ) , EHWEs per occupied bed per hour , and patient-to-nurse ratios . In addition , from May 26 through June 26 ( baseline period ) and from November 2 through December 8 ( follow-up period ) , live observers stationed daily for r and om 4-hour intervals in the MICU and the SICU counted actual h and washing episodes ( CHWEs ) . The intervention consisted of posting in the SICU , but not in the MICU , a graph showing the weekly EHWEs per occupied bed per hour for the preceding 5 weeks . RESULTS Directly counted h and washing fell in the SICU from a baseline of 2.68+/-0.72 ( mean + /- st and ard deviation ) episodes per occupied bed per hour to 1.92+/-1.35 in the follow-up period . In the MICU , episodes fell from 2.58+/-0.95 ( baseline ) to 1.74+/-0.69 . In the MICU , the withdrawal of live observers was associated with a decrease in estimated episodes from 1.36+/-0.49 at baseline to 1.01+/-0.36 , with a return to 1.16+/-0.50 when the observers returned . In the SICU , a similar decrease did not persist throughout a period of feedback . Estimated h and washing correlated negatively with the patient-to-nurse ratio ( r = -0.35 for the MICU , r = -0.46 for the SICU ) . CONCLUSIONS Sustained feedback on h and washing failed to produce a sustained improvement . Live observers were associated with increased h and washing , even when they did not offer feedback . H and washing decreased when the patient-to-nurse ratio increased BACKGROUND We sought to determine the long-term effect of a multifaceted infection-control intervention to reduce the incidence of p and rug-resistant Acinetobacter baumannii infection in a Thai tertiary care center . METHODS A 3-year , prospect i ve , controlled , quasi-experimental study was conducted in medical intensive care , surgical intensive care , and coronary care units for a 1-year period before intervention ( period 1 ) , a 1-year period after intervention ( period 2 ) , and a 1-year follow-up period ( period 3 ) . The interventions in period 2 included strictly implementing contact isolation pre caution s and appropriate h and hygiene , active surveillance , cohorting patients who were colonized or infected with p and rug-resistant A. baumannii , and environmental cleaning with 1:100 sodium hypochlorite solution . All interventions were continued in period 3 , but environmental cleaning solutions were changed to detergent and phenolic agents . RESULTS Before the intervention , the rate of p and rug-resistant A. baumannii colonization and /or infection was 3.6 cases per 1000 patient-days . After the intervention , the rate of p and rug-resistant A. baumannii colonization and /or infection decreased by 66 % in period 2 ( to 1.2 cases per 1000 patient-days ; P < .001 ) and by 76 % in period 3 ( to 0.85 cases per 1000 patient-days ; P < .001 ) . The monthly hospital antibiotic cost of treating p and rug-resistant A. baumannii colonization and /or infection and the hospitalization cost for each patient in the intervention units were also reduced by 36%-42 % ( P < .001 ) and 25%-36 % ( P < .001 ) , respectively , during periods 2 and 3 . CONCLUSIONS A multifaceted intervention featuring active surveillance and environmental cleaning result ed in sustained reductions in the rate of p and rug-resistant A. baumannii colonization and infection , the cost of antibiotic therapy , and the cost of hospitalization among intensive care unit patients in a developing country OBJECTIVE To study the frequency of h and washing and the effects of an educational program . DESIGN A prospect i ve study . SETTING A tertiary-care , pediatric hospital . PARTICIPANTS Three divisions ( two general pediatric wards and one infectious disease ward ) . The personnel observed included 60 medical staff ( interns , residents , and attending , including consulting , physicians ) , 37 nurses , and 15 paramedical staff . INTERVENTIONS The study was carried out in 5 phases : ( 1 ) unobtrusive observation to obtain a baseline h and washing rate ; ( 2 ) observation after written notification ; ( 3 ) observation after providing motivating devices : movies , brochures , posters ; ( 4 ) discontinuation of observation and motivation ; ( 5 ) unobtrusive observation , to obtain a residual h and washing rate . RESULTS During this study , 1,123 patient contacts were observed . The baseline h and washing rates before and after patient contact were 52 % and 49 % , respectively . During phase 2 , h and washing rates before and after patient contact increased slightly to 56 % and 52 % , respectively . During phase 3 , rates increased to 74 % and 69 % ( P < .01 ) . However , rates fell during the final phases to 49 % and 52 % , respectively ( P < .01 ) . There were no significant differences among hospital staff in any phase of this study ( P > .05 ) . CONCLUSIONS Constant motivation , using movies , brochures , and posters , transiently increased the frequency of h and washing among the house staff of a tertiary-care facility ; however , to be effective , this motivation needs to be sustained BACKGROUND H and hygiene ( HH ) compliance among health care workers ( HCWs ) has been historically low and hampered by poor surveillance methods . This study evaluated the use of an electronic device to measure and impact HH compliance . METHODS The study is a prospect i ve , interventional study in a 30-bed academic medical center hematology unit . Phase I of the study monitored baseline HH compliance , and phase II monitored HH compliance using automatic alerts . The primary outcome measure was HH compliance , and the secondary end point was nosocomial transmission of vancomycin-resistant Enterococcus ( VRE ) . RESULTS Eight thous and two hundred thirty-five HH opportunities were measured during the study , with HH compliance improvement from 36.3 % at baseline to 70.1 % during phase II . The use of audible alerts improved HH compliance for both the day shift ( odds ratio [ OR ] , 3.6 ) and the night shift ( OR , 5.9 ) , as well as across rooms with higher HCW traffic ( OR , 1.6 ) and lower HCW traffic ( OR , 3.2 ) . CONCLUSION Electronic devices can effectively monitor HH compliance among HCWs and facilitate improved adherence to guidelines . Electronic devices improve HH compliance regardless of time of day or room location . The development of innovative devices to improve HH is required to vali date the long-term implication s of this methodology BACKGROUND There were 3 objectives for this prospect i ve quasiexperimental study . The first was to determine the effect of mentor 's h and hygiene practice s on student 's h and hygiene rates during clinical rotations . The second was to assess the difference in h and hygiene rates for students with and without prior medical experience . The third was to assess the student 's opinion and beliefs regarding h and hygiene . METHODS Sixty students enrolled in a certified nursing program were selected to participate in the study . Each study group was observed twice during the 30-day span . The first observational period was conducted on day 1 of clinical rotation . The second observational period was conducted on day 30 of clinical rotation . Students were observed for h and hygiene . Also assessed were medical experience , sex , gloving , age , and mentor 's h and hygiene practice s. After observational period 2 , a brief question naire was given to students to determine their opinion and beliefs regarding h and hygiene . The question naire was divided into 5 sections : student 's commitment to h and hygiene , their perception of h and hygiene inconvenience , the necessity of h and hygiene , the student 's ability to perform h and hygiene , and their opinion on the frequency of medical staff 's h and hygiene . RESULTS The mentor 's practice of h and hygiene was the strongest predictor of the student 's rate of h and hygiene for both observational periods ( P < .01 ) . Furthermore , students without prior medical experience had a significant increase in h and hygiene rates when comparing observational period 1 to observational period 2 ( P < .01 ) . Glove usage was associated with increased h and hygiene rates by 50 % during observational period 1 ( P = .01 ) and 44 % during observational period 2 ( P < .01 ) . Male students during observational period 1 practice d h and hygiene 30 % less often than female students ( P < .01 ) ; however , during observational period 2 , there was no significant difference between h and hygiene rates for males and females ( P = .82 ) . Question naires were completed by 47 students , who reported a strong commitment to h and hygiene , belief in its necessity , and ability to perform h and hygiene ( with scores in the high 90s on a 10 to 100 rating scale ) . CONCLUSION Mentor 's use of h and hygiene and glove usage was associated with increased h and hygiene among students . Even though students reported strongly positive attitudes toward h and hygiene , students had a low overall rate of h and hygiene H and hygiene prevents cross infection in hospi tals , however adherence to guidelines is commonly poor . The h and -hygiene promotion programme started on May 2004 at the University Hospital of Liège after a baseline survey of compliance . We attempted to promote h and hygiene and most par ticularly alcohol-based h and disinfection . We measured MRSA transmission rates and consumption of alcohol-based h and rub solution and soap in parallel . During the campaign , consump tion of alcohol-based h and rub solution and soap increased by 56 % and 24 % respectively and MRSA transmission rates decreased from 11,04 to 7,07 cases per 1000 admissions OBJECTIVE To determine the effectiveness of World Health Organization ( WHO ) multimodal strategy in promoting h and hygiene ( HH ) among healthcare workers ( HCWs ) in long-term care facilities ( LTCFs ) . DESIGN Cluster-r and omized controlled trial . SETTING Eighteen homes for the elderly in Hong Kong were r and omly allocated to 2 intervention arms and a control arm . Direct observation of HH practice was conducted by trained nurses . Either h and rubbing with alcohol-based h and rub ( ABHR ) or h and washing with liquid soap and water was counted as a compliant action . Disease notification data during 2007 - 2010 were used to calculate incidence rate ratio ( IRR ) . PARTICIPANTS Managers and HCWs of the participating homes . INTERVENTIONS The WHO multimodal strategy was employed . All intervention homes were supplied with ABHR ( WHO formulation I ) , ABHR racks , pull reels , HH posters and reminders , a health talk , video clips , training material s , and performance feedback . The only difference was that intervention arms 1 and 2 were provided with slightly powdered and powderless gloves , respectively . RESULTS A total of 11,669 HH opportunities were observed . HH compliance increased from 27.0 % to 60.6 % and from 22.2 % to 48.6 % in intervention arms 1 and 2 , respectively . Both intervention arms showed increased HH compliance after intervention compared to controls , at 21.6 % compliance ( both [ Formula : see text ] ) . Provision of slightly powdered versus powderless gloves did not have any significant impact on ABHR usage . Respiratory outbreaks ( IRR , 0.12 ; 95 % confidence interval [ CI ] , 0.01 - 0.93 ; [ Formula : see text ] ) and methicillin-resistant Staphylococcus aureus infections requiring hospital admission ( IRR , 0.61 ; 95 % CI , 0.38 - 0.97 ; [ Formula : see text ] ) were reduced after intervention . CONCLUSIONS A promotion program applying the WHO multimodal strategy was effective in improving HH among HCWs in LTCFs CONTEXT Under routine hospital conditions h and washing compliance of health care workers including nurses , physicians , and others ( eg , physical therapists and radiologic technicians ) is unacceptably low . OBJECTIVES To investigate the efficacy of an education/ feedback intervention and patient awareness program ( cognitive approach ) on h and washing compliance of health care workers ; and to compare the acceptance of a new and increasingly accessible alcohol-based waterless h and disinfectant ( technical approach ) with the st and ard sink/soap combination . DESIGN A 6-month , prospect i ve , observational study . SETTING One medical intensive care unit ( ICU ) , 1 cardiac surgery ICU , and 1 general medical ward located in a 728-bed , tertiary care , teaching facility . PARTICIPANTS Medical caregivers in each of the above setting s. INTERVENTIONS Implementation of an education/ feedback intervention program ( 6 in-service sessions per each ICU ) and patient awareness program , followed by a new , increasingly accessible , alcohol-based , waterless h and antiseptic agent , initially available at a ratio of 1 dispenser for every 4 patients and subsequently 1 for each patient . MAIN OUTCOME MEASURE Direct observation of h and -washing for 1575 potential opportunities monitored over 120 hours r and omized for both time of day and bed locations . RESULTS Baseline h and washing compliance before and after defined events was 9 % and 22 % for health care workers in the medical ICU and 3 % and 13 % for health care workers in the cardiac surgery ICU , respectively . After the education/feedback intervention program , h and washing compliance changed little ( medical ICU , 14 % [ before ] and 25 % [ after ] ; cardiac surgery ICU , 6 % [ before ] and 13 % [ after ] ) . Observations after introduction of the new , increasingly accessible , alcohol-based , waterless h and antiseptic revealed significantly higher h and washing rates ( P<.05 ) , and h and washing compliance improved as accessibility was enhanced-before 19 % and after 41 % with 1 dispenser per 4 beds ; and before 23 % and after 48 % with 1 dispenser for each bed . CONCLUSIONS Education/feedback intervention and patient awareness programs failed to improve h and washing compliance . However , introduction of easily accessible dispensers with an alcohol-based waterless h and washing antiseptic led to significantly higher h and washing rates among health care workers Obtaining study leave is becoming difficult for clinical nurses in the current economic climate , but the need to develop new clinical skills and to maintain existing good practice remains of prime importance to patient care and will become m and atory with the advent of post- registration education and practice ( PREP ) in the UK . The ward is widely acknowledged as the best venue for learning clinical skills by nurse educationalists and for many nurses is the preferred learning environment . The feasibility of using a ward-based teaching package to enhance nurses ' compliance with key infection control pre caution s ( h and decontamination , the use of gloves and the safe h and ling and disposal of sharp instruments ) was tested in a quasi-experimental research study conducted on matched surgical wards in a teaching hospital , controlling for variables likely to influence performance ( knowledge , availability of re sources to perform infection control , previous opportunity to develop infection control expertise and nursing workload ) . Nurses on two wards received the intervention ( experimental group ) . The remaining wards , which received no intervention , operated as controls . The ward-based sessions consisted of a carefully planned sequence of theory and practical demonstration delivered to qualified nurses in the clinical environment at convenient times selected by the ward managers . Performance of infection control pre caution s was audited before the intervention and 3 months afterwards . The sessions were well evaluated and the clinical environment was considered suitable for teaching by the nurses , but heavy and unpredictable workload prevented the teaching programme from being implemented as planned . The analysis of covariance failed to detect any changes in performance between nurses in the control and experimental groups . The implication s of the study findings are discussed to help develop creative new ways of strengthening ward-based educational programmes Objective . To evaluate the effects of the introduction of an alcohol-based h and gel and multifaceted quality improvement ( QI ) interventions on h and hygiene ( HH ) compliance . Design . Interventional , r and omized cohort study with four study phases ( baseline ; limited intervention in two units ; full intervention in three units ; washout phase ) , performed in three intensive care units at a pediatric referral hospital . Methods . During 724 thirty-minute daytime monitoring sessions , a nonidentified observer witnessed 12 216 opportunities for HH and recorded compliance . Interventions . Introduction of an alcohol-based h and gel ; multifaceted QI interventions ( educational program , opinion leaders , performance feedback ) . Results . Baseline compliance decreased after the first 2 weeks of observation from 42.5 % to 28.2 % ( presumably because of waning of a Hawthorne effect ) , further decreased to 23.3 % in the limited intervention phase and increased to 35.1 % after the introduction of a h and gel with QI support in all three units ( P < 0.001 ) . The rise in compliance persisted in the last phase ( compliance , 37.2 % ) ; however , a gradual decline was observed during the final weeks . Except for the limited intervention phase , compliance achieved through st and ard h and washing and glove use remained stable around 20 and 10 % , respectively , whereas compliance achieved through gel use increased to 8 % ( P < 0.001 ) . After adjusting for confounding , implementation of the h and gel with QI support remained significantly associated with compliance ( odds ratio , 1.6 ; 95 % confidence interval , 1.4 to 1.8 ) . In a final survey completed by 62 staff members , satisfaction with the h and gel was modest ( 45 % ) . Conclusions . We noted a statistically significant , modest improvement in compliance after introduction of an alcohol-based h and gel with multifaceted QI support . When appropriately implemented , alcohol-based HH may be effective in improving compliance BACKGROUND Use of an alcohol-based h and rub for h and hygiene has recently been recommended by the Centers for Disease Control and Prevention . However , the proper technique for using h and rub has not been well described and is not routinely taught in hospitals . OBJECTIVE To evaluate the impact of training on proper technique as outlined by the European St and ard for testing alcohol-based h and rubs ( European Norm 1500 ) in a clinical study . DESIGN , SETTING , AND PATIENTS Prospect i ve study including 180 healthcare workers ( HCWs ) in a 450-bed , university-affiliated geriatric hospital where alcohol-based h and rub was introduced in the late 1970s . INTERVENTION Structured training program in h and hygiene with alcohol-based h and rub . Technique for using h and rub was tested by the addition of a fluorescent dye to the disinfectant and the number of areas missed was quantified by a vali date d visual assessment method . In addition , the number of bacteria eradicated was estimated by calculating the difference between the log(10 ) number of colony-forming units ( cfu ) of bacteria on the fingertips before and after the procedure , and reported as reduction factor ( RF ) . MAIN OUTCOME MEASURE Log(10 ) cfu bacterial counts on fingertips before and after training in the appropriate technique for using h and rub . RESULTS At baseline , only 31 % of HCWs used proper technique , yielding a low RF of 1.4 log(10 ) cfu bacterial count . Training improved HCW compliance to 74 % and increased the RF to 2.2 log(10 ) cfu bacterial count , an increase of almost 50 % ( P<.001 ) . Several factors , such as applying the proper amount of h and rub , were significantly associated with the increased RF . CONCLUSION These results demonstrate that education on the proper technique for using h and rub , as outlined in EN 1500 , can significantly increase the degree of bacterial killing BACKGROUND This study evaluated the impact of 2 models of educational intervention on rates of central venous catheter-associated bloodstream infections ( CVC-BSIs ) . METHODS This was a prospect i ve observational study conducted between January 2005 and June 2007 in 2 medical intensive care units ( design ated ICU A and ICU B ) in a large teaching hospital . The study was divided into in 3 periods : baseline ( only rates were evaluated ) , preintervention ( question naire to evaluate knowledge of health care workers [ HCWs ] and observation of CVC care in both ICUs ) , and intervention ( in ICU A , tailored , continuous intervention ; in ICU B , a single lecture ) . The preintervention and intervention periods for each ICU were compared . RESULTS During the preintervention period , 940 CVC-days were evaluated in ICU A and 843 CVC-days were evaluated in ICU B. During the intervention period , 2175 CVC-days were evaluated in ICU A and 1694 CVC-days were evaluated in ICU B. Questions regarding CVC insertion , disinfection during catheter manipulation , and use of an alcohol-based product during dressing application were answered correctly by 70%-100 % HCWs . Nevertheless , HCWs ' adherence to these practice s in the preintervention period was low for CVC h and ling and dressing , h and hygiene ( 6%-35 % ) , and catheter hub disinfection ( 45%-68 % ) . During the intervention period , HCWs ' adherence to h and hygiene was 48%-98 % , and adherence to hub disinfection was 82%-97 % . CVC-BSI rates declined in both units . In ICU A , this decrease was progressive and sustained , from 12 CVC-BSIs/1000 CVC-days at baseline to 0 after 9 months . In ICU B , the rate initially dropped from 16.2 to 0 CVC-BSIs/1000 CVC-days , but then increased to 13.7 CVC-BSIs/1000 CVC-days . CONCLUSION Personal customized , continuous intervention seems to develop a " culture of prevention " and is more effective than single intervention , leading to a sustained reduction of infection rates CONTEXT H and washing is considered the single most important nosocomial infection-control strategy , yet compliance rarely meets levels recommended by infection control authorities . OBJECTIVES To determine whether placement of h and hygiene foam dispensers in more conspicuous positions and closer proximity to patients would increase use of infection control agents as measured by volume of product used . Further , to ascertain the influence of dispenser placement vs the number of dispensers available on usage by volume . METHODS This prospect i ve , observational study conducted in an intensive care unit was composed of three observation periods . A control period with st and ard agent dispenser location ( 8 dispensers ) was followed by two experimental periods : ( 1 ) " conspicuous and immediate proximity to patient " placement ( 16 dispensers ) and ( 2 ) st and ard locations with a dramatic increase in the number of dispensers ( 36 dispensers ) . RESULTS Volume of use for alcohol-based h and hygiene agent during the three observation periods revealed a statistically significant increase in daily consumption after conspicuous and proximate positioning of dispensers ( P<.001 ) . However , increasing the number of dispensers did not increase agent use ( P=.196 ) . CONCLUSION More conspicuous placement of dispensers containing alcohol-based h and hygiene agent ( ie , immediate proximity to patients ) result ed in statistically and clinical ly significant increases in product usage . An increase in the number of dispensers did not increase usage . The impact of dispenser positioning on usage by volume for these highly effective products should be considered when planning and implementing intensive care unit infection-control policies OBJECTIVE We conducted an intervention study to assess the impact of the use of an alcohol-chlorhexidine-based h and sanitizer on surgical site infection ( SSI ) rates among neurosurgical patients in Ho Chi Minh City , Vietnam . DESIGN A quasi-experimental study with an untreated control group and assessment of neurosurgical patients admitted to 2 neurosurgical wards at Cho Ray Hospital between July 11 and August 15 , 2000 ( before the intervention ) , and July 14 and August 18 , 2001 ( after the intervention ) . A h and sanitizer with 70 % isopropyl alcohol and 0.5 % chlorhexidine gluconate was introduced , and healthcare workers were trained in its use on ward A in September 2000 . No intervention was made in ward B. Centers for Disease Control and Prevention definitions of SSI were used . Patient SSI data were collected on st and ardized forms and were analyzed using Stata software ( Stata ) . RESULTS A total of 786 patients were enrolled : 377 in the period before intervention ( 156 in ward A and 221 in ward B ) and 409 in the period after intervention ( 159 in ward A and 250 in ward B ) . On ward A after the intervention , the SSI rate was reduced by 54 % ( from 8.3 % to 3.8 % ; P=.09 ) , and more than half of superficial SSIs were eliminated ( 7 of 13 vs 0 of 6 in ward B ; P=.007 ) . On ward B , the SSI rate increased by 22 % ( from 7.2 % to 9.2 % ; P=.8 ) . In patients without SSI , the median postoperative length of stay and the duration of antimicrobial use were reduced on ward A ( both from 8 to 6 days ; P<.001 ) but not on ward B. CONCLUSIONS Our study demonstrates that introduction of a h and sanitizer can both reduce SSI rates in neurosurgical patients , with particular impact on superficial SSIs , and reduce the overall postoperative length of stay and the duration of antimicrobial use . H and hygiene programs in developing countries are likely to reduce SSI rates and improve patient outcomes BACKGROUND Without protective practice s such as Universal Pre caution s , health care workers are at substantial risk for bloodborne infection , especially in areas such as Thail and with high prevalence of HIV infection . The purpose of this study was to evaluate the effectiveness of a peer feedback program ( PFP ) on h and washing and glove wearing ( HW/GW ) among Thai health care workers . METHODS Subjects ( N = 91 ) were r and omly assigned to receive PFP versus no treatment . By using a checklist , peer observers rated HW/GW compliance in their coworkers during patient care . For 1 month , the investigator posted a report of compliance behaviors from each 3 days of observations . HW/GW was also assessed by the investigator by direct observation at 1 month before the intervention , during the intervention period , and 1 month after the intervention . RESULTS Baseline HW/GW rates for the PFP and control groups were 49.2 % and 61.5 % , respectively . The PFP group had a significantly higher adjusted compliance rate than the control group during the intervention period ( P = .0001 ) . However , there was no significant difference in the compliance scores obtained 1 month after the intervention . CONCLUSIONS The PFP was effective during the intervention period , but there was no retention of effect . Therefore , adjunct methods should be sought to promote retention of effect PURPOSE To evaluate the effect of an educational training program for hospital nurses on universal pre caution s in Changsha , Hunan Province , People 's Republic of China . METHOD Using a quasi-experimental design , 50 of 100 r and omly selected hospital nurses were r and omly assigned to receive an educational intervention . Question naires were administered to the 100 nurses prior to and 4 months after the training . FINDINGS Knowledge , practice , and behaviors related to universal pre caution s and the prevalence of hepatitis B immunization improved among nurses in the group who received training . No significant change in the frequency of glove use was found . Underreporting of sharps injuries to hospital authorities continued in both groups . CONCLUSION Although educational training significantly improved Chinese nurses ' knowledge , practice , and behavior related to universal pre caution s , there remains room for improvement in glove use and needlestick injury reporting |
2,376 | 28,403,216 | CONCLUSIONS Aspirin use in PVD might not be associated with improved cardiovascular outcomes or worse bleeding outcomes . | BACKGROUND Although considered a cornerstone therapy , the efficacy and safety of aspirin for prevention of ischemic events in patients with peripheral vascular disease ( PVD ) remains uncertain .
Thus , we aim ed to evaluate aspirin use in both symptomatic and asymptomatic patients with PVD . | Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To determine whether aspirin and antioxidant therapy , combined or alone , are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease . Design Multicentre , r and omised , double blind , 2 × 2 factorial , placebo controlled trial . Setting 16 hospital centres in Scotl and , supported by 188 primary care groups . Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease . Interventions Daily , 100 mg aspirin tablet plus antioxidant capsule ( n=320 ) , aspirin tablet plus placebo capsule ( n=318 ) , placebo tablet plus antioxidant capsule ( n=320 ) , or placebo tablet plus placebo capsule ( n=318 ) . Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke , non-fatal myocardial infa rct ion or stroke , or amputation above the ankle for critical limb ischaemia ; and death from coronary heart disease or stroke . Results No evidence was found of any interaction between aspirin and antioxidant . Overall , 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2 % v 18.3 % ) : hazard ratio 0.98 ( 95 % confidence interval 0.76 to 1.26 ) . Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7 % v 5.5 % ) : 1.23 ( 0.79 to 1.93 ) . Among the antioxidant groups 117 of 640 ( 18.3 % ) primary events occurred compared with 116 of 636 ( 18.2 % ) in the no antioxidant groups ( 1.03 , 0.79 to 1.33 ) . Forty two ( 6.6 % ) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7 % ) in the no antioxidant groups ( 1.21 , 0.78 to 1.89 ) . Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied . Trial registration Current Controlled Trials IS RCT N53295293 A r and omized , double-blind clinical trial was design ed to assess the effect of aspirin ( ASA ) alone or in combination with dipyridamole ( DIP ) on the patency rates of exp and ed PTFE grafts placed in the infrainguinal position . Forty-nine patients were r and omized into three groups who received three times daily either two placebos ( 17 patients ) , 325 mg ASA and placebo ( 16 patients ) , or 325 mg ASA and 75 mg DIP ( 16 patients ) . The patients were seen at 3-month intervals for 1 year , and coded medication bottles were dispensed and returned pills counted to assess patient compliance . Treatment failure was defined as the first graft occlusion . The data were analyzed using the Breslow statistic for progressively censored survival type data . The 1-year cumulative patency rate for the entire series was 59 % . The rates for above-knee grafts in the ASA group ( 100 % ) and the ASA/DIP group ( 100 % ) were significantly higher than the rates for the placebo group ( 50 % ) ( P = 0.05 ) . The 1-year cumulative patency rates for patients with below-knee grafts were not statistically different among the groups , although the patients who received ASA alone had a higher rate than did the other two groups ( 65 % versus 21 % for placebo and 19 % for ASA/DIP ) . There were fewer occlusions in the above-knee grafts as compared to below-knee grafts in all groups , but the differences were statistically significant only in the ASA/DIP group . There were no statistical differences between the two active treatment groups The effect of 7-mono-hydroxyethylrutoside and its combination with acetylsalicylic acid was evaluated in a controlled clinical trial , performed in 105 patients with obliterative atherosclerosis of the lower limbs , and using non-invasive measurement of peripheral haemodynamic parameters -- blood flow during reactive hyperaemia and ankle systolic blood pressure . Patients , r and omized into three groups , received either placebo or 7-mono-hydroxyethylrutoside alone or in combination with acetylsalicylic acid for 12 months . The placebo group showed a decrease in maximum calf blood flow and a decrease in ankle systolic pressure . Administration of 7-mono-hydroxyethylrutoside did not lead to any significant changes in systolic pressure but there was a decrease in the maximum calf blood flow . There were no statistically significant changes in patients receiving the 7-mono-hydroxyethylrutoside and acetylsalicylic acid combination who , by contrast , showed a tendency to increased values of the parameters measured Thirty one r and omised trials of antiplatelet treatment for patients with a history of transient ischaemic attack , occlusive stroke , unstable angina , or myocardial infa rct ion were identified . Six were still in progress , and the results of the remaining 25 were review ed . They included a total of some 29 000 patients , 3000 of whom had died . Overall , allocation to antiplatelet treatment had no apparent effect on non-vascular mortality but reduced vascular mortality by 15 % ( SD 4 % ) and non-fatal vascular events ( stroke or myocardial infa rct ion ) by 30 % ( 4 % ) . This suggested that with good compliance these treatments might reduce vascular mortality by about one sixth , other vascular events by about a third , and total vascular events by about a quarter . There was no significant difference between the effects of the different types of antiplatelet treatment tested ( 300 - 325 mg aspirin daily , higher aspirin doses , sulphinpyrazone , or high dose aspirin with dipyridamole ) , nor between the effects in patients with histories of cerebral or cardiac disease . Thus antiplatelet treatment can reduce the incidence of serious vascular events by about a quarter among a wide range of patients at particular risk of occlusive vascular disease . The balance of risk and benefit , however , might be different for “ primary ” prevention among people at low absolute risk of occlusive disease if antiplatelet treatment produced even a small increase in the incidence of cerebral haemorrhage Background : In patients with symptomatic peripheral artery disease with a history of limb revascularization , the optimal antithrombotic regimen for long-term management is unknown . Methods : The EUCLID trial ( Examining Use of Ticagrelor In PAD ) r and omized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily . Patients were enrolled based on an abnormal ankle-brachial index ⩽0.80 or a previous lower extremity revascularization . This analysis focuses on the 7875 ( 57 % ) patients enrolled based on the previous lower extremity revascularization criterion . Patients could not be enrolled within 30 days of most recent revascularization , and patients with an indication for dual antiplatelet therapy were excluded . The primary efficacy end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . The primary safety end point was major bleeding . Results : Patients with a previous revascularization had a mean age of 66 years , 73 % were male , and the median baseline ankle-brachial index was 0.78 . After adjustment for baseline characteristics , patients enrolled based on previous revascularization had similar rates of the primary composite end point ( hazard ratio [ HR ] 1.10 , 95 % confidence interval [ CI ] 0.98–1.23 , P=0.12 ) and statistically significantly higher rates of myocardial infa rct ion ( HR 1.29 , 95 % CI 1.08–1.55 , P=0.005 ) and acute limb ischemia ( HR 4.23 , 95 % CI 2.86–6.25 , P<0.001 ) when compared with patients enrolled based on ankle-brachial index criteria . No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point ( 11.4 % vs 11.3 % ; HR 1.01 , 95 % CI 0.88–1.15 ; P=0.90 ) , all-cause mortality ( 9.2 % vs 9.2 % ; HR 0.99 , 95 % CI 0.86–1.15 ; P=0.93 ) , acute limb ischemia ( 2.5 % vs 2.5 % ; HR 1.03 , 95 % CI 0.78–1.36 ; P=0.84 ) , or major bleeding ( 1.9 % vs 1.8 % ; HR 1.15 , 95 % CI 0.83–1.59 ; P=0.41 ) . The median duration of follow-up was ≈30 months . Conclusions : After adjustment for baseline characteristics , patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infa rct ion and acute limb ischemia , with similar composite rates of cardiovascular death , myocardial infa rct ion , and stroke when compared with patients enrolled based on the ankle-brachial index criterion . No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01732822 In this prospect i ve study 364 patients were subjected to different types of arterial reconstructive surgery . The patients were r and omly divided into four groups according to the type of antithrombotic medication given . During the hospitalization period there were no reocclusions in the dipyridamole/ASA group of 93 patients compared with 12 reocclusions in the control group of 86 patients . The difference was statistically highly significant . The difference between the control group and the given dipyridamole or ASA was not statistically significant . Dipyridamole and ASA were tolerated well by the patients in this clinical trial . This was the first clinical investigation to prove the effectiveness of dipyridamole and ASA medication in the prevention of reocclusions in arterial reconstructive bypass surgery 240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities . Patients were r and omised into 1 of 3 treatment groups : aspirin 330 mg ; dipyridamole 75 mg and aspirin 330 mg ; or matching placebo 3 times daily . The duration of treatment was 2 years . Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed . 199 patients completed the study according to the trial protocol . The serial arteriograms were assessed in pairs qualitatively , by means of simple comparative viewing , and semiquantitatively with Bollinger 's score system . Progression of the disease was most pronounced in the placebo-treated group , less so in the aspirin-treated group , and least of all in the dipyridamole- and -aspirin group . Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation CONTEXT A low ankle brachial index ( ABI ) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events . Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments . OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population . DESIGN , SETTING , AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind r and omized controlled trial conducted from April 1998 to October 2008 , involving 28,980 men and women aged 50 to 75 years living in central Scotl and , free of clinical cardiovascular disease , recruited from a community health registry , and had an ABI screening test . Of those , 3350 with a low ABI ( < or = 0.95 ) were entered into the trial , which was powered to detect a 25 % proportional risk reduction in events . INTERVENTIONS Once daily 100 mg aspirin ( enteric coated ) or placebo . MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization . Two secondary end points were ( 1 ) all initial vascular events defined as a composite of a primary end point event or angina , intermittent claudication , or transient ischemic attack ; and ( 2 ) all-cause mortality . RESULTS After a mean ( SD ) follow-up of 8.2 ( 1.6 ) years , 357 participants had a primary end point event ( 13.5 per 1000 person-years , 95 % confidence interval [ CI ] , 12.2 - 15.0 ) . No statistically significant difference was found between groups ( 13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group ; hazard ratio [ HR ] , 1.03 ; 95 % CI , 0.84 - 1.27 ) . A vascular event comprising the secondary end point occurred in 578 participants ( 22.8 per 1000 person-years ; 95 % CI , 21.0 - 24.8 ) and no statistically significant difference between groups ( 22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group ; HR , 1.00 ; 95 % CI , 0.85 - 1.17 ) . There was no significant difference in all-cause mortality between groups ( 176 vs 186 deaths , respectively ; HR , 0.95 ; 95 % CI , 0.77 - 1.16 ) . An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants ( 2.5 per 1000 person-years ) in the aspirin group and 20 ( 1.5 per 1000 person-years ) in the placebo group ( HR , 1.71 ; 95 % CI , 0.99 - 2.97 ) . CONCLUSION Among participants without clinical cardiovascular disease , identified with a low ABI based on screening a general population , the administration of aspirin compared with placebo did not result in a significant reduction in vascular events . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N66587262 A prospect i ve controlled study of 144 patients with peripheral obstructive arterial disease was undertaken to evaluate the efficacy of acetylsalicylic acid ( ASA ) treatment ( 250 mg daily ) on the outcome after lower limb arterial surgery which mainly involved endarterectomy . By r and om enrollment , 2 groups of 72 patients were formed after the surgery . Patients with ASA treatment for 3 months , starting from the seventh postoperative day , were compared with patients who were not treated with ASA . The patients in both groups had similar characteristics as to sex ratio , age , concomitant diseases , preoperative arm-ankle systolic blood pressure index , and type and primary success of the reconstruction . Forty-seven of the ASA-treated and 48 of the untreated patients reported to continue cigarette smoking . Postoperative ASA-treatment protected against local adverse events which occurred in 15 patients ( 21 % ) of the ASA-treated group compared with 31 patients ( 43 % ) of the untreated group ( p<0.01 ) . Among heavy smokers ( > 15 cigarettes/day ) the efficacy of antiplatelet treatment was not detectable . These results imply that , in patients with peripheral arterial disease , ASA prevents platelet interaction to endarterectomized and atherosclerotic lower limb arteries thereby affecting the subsequent risk of occlusion ; however , heavy cigarette smoking , which is very common among patients with peripheral arterial disease , counteracts the local antithrombotic potency of ASA.RésuméL'effet de l'administration de 250 mg d'acide acétyl-salicilique ( AAS ) par jour sur les résultats de chirurgie artérielle des membres inférieurs , le plus souvent endartériectomie , a été évalué par une étude prospect i ve et contrôlée chez 144 patients ayant une maladie occlusive artérielle périphérique . Deux groupes de 72 patients ont été formés par r and omisation , l'un traité par l'AAS pendant trois mois à partir du 7ème jour post-opératoire , l'autre sans ce traitement . Les deux groupes étaient similaires quant au sexe ratio , l'âge , les maladies concomitantes , l'index systolique bras-cheville pré-opératoire , le type et la perméabilité primaire de l'intervention . Quarante-sept des patients traités et 48 des patients sans traitement ont continué de fumer . Il y a eu 15 patients ( 21 % ) dans le groupe AAS qui ont eu une complication , comparés à 31 patients ( 43 % ) dans le groupe non traité ( p<0.01 ) . Il n'y avait pas de différence des résultats parmi les patients qui fumaient plus de 15 cigarettes par jour . Les résultats impliquent que l'AAS chez l'endartériectomisé ou le patient avec des artères athérosclérotiques prévient l'interaction plaquettaire et que ce traitement influe sur le risque d'obstruction vasculaire . Cependant , la consommation élevée du tabac , qui est souvent plus importante chez le patient avec maladie artérielle périphérique contrebalance les effets locaux d'AAS.ResumenSe emprendió un estudio prospect ivo y controlado sobre 144 pacientes con enfermedad arterial obstructiva periférica con el fin de evaluar la eficacia del ácido acetil salicílico ( ASA ) en el result ado final después de cirugía arterial sobre la extremidad inferior , principalmente endarterectomía . Se constituyeron , después de la cirugía y mediante r and omización , 2 grupos de 72 pacientes cada uno . Los pacientes tratados con ASA por 3 meses , comenz and o en el séptimo día portoperatorio , fueron comparados con los pacientes que no recibieron ASA . Los pacientes en los 2 grupos tuvieron las mismas características en cuanto a sexo , edad , enfermedades concomitantes , índice preoperatorio de presión sistólica brazo-tobillo y tipo y éxito primario de la reconstrucción . Cuarenta y siete de los pacientes tratados con ASA y 48 de los no tratados continuaron fum and o cigarrillo . El tratamiento postoperatorio con ASA protegió contra los efectos locales adversos , que se presentaron en 15 casos ( 21 % ) , en comparación con 31 casos ( 43 % ) en el grupo que no fue tratado con ASA ( p<0.01 ) . Entre los fumadores empedernidos ( > 15 cigarrillos/día ) no apareció evidente la eficacia del tratamiento antiplaquetario . Estos result ados implican que en pacientes con enfermedad arterial periférica el ASA previene las interreacciones plaquetarias en las arterias endarterectomizados y arterioscleróticas de los miembros inferiores , con lo cual se reduce el riesgo de oclusión consecuente . Sin embargo , el hábito intenso de fumar , que es muy común en los pacientes con enfermedad arterial periférica , anula la potencia antitrombocítica local del ASA OBJECTIVES We sought to determine whether aspirin withdrawal is an encountered situation in coronary disease patients who relapsed . BACKGROUND Despite the recognized benefits of aspirin in coronary disease , and because of the threat of bleeding or poor compliance , aspirin intake is sometimes stopped . It is not known whether withdrawal of aspirin can be harmful in coronary-disease patients . METHODS Between September 1999 and April 2002 , a total of 1,236 patients hospitalized for acute coronary syndrome ( ACS ) were question ed in order to determine whether aspirin intake had been interrupted . RESULTS Fifty-one of these ACSs occurred within 1 month after aspirin withdrawal . This represents 4.1 % of all coronary events but 13.3 % of recurrences . Among those patients who relapsed , the incidence of ST-segment elevation ACS was higher in those who stopped aspirin when compared to the 332 patients who did not stop aspirin ( 39 % vs. 18 % ; p = 0.001 ) . Ten ( 20 % ) cases involved a thrombosis of an uncoated stent implanted on average 15.5 + /- 6.5 months previously . Mean delay between aspirin withdrawal and the acute coronary event was 10 + /- 1.9 days . Reasons for aspirin withdrawal included minor surgery in 7 cases , fibroscopy in 8 cases , dental treatment in 13 cases , bleeding in 3 cases , and patient non-compliance in 20 cases . CONCLUSIONS Our results support the hypothesis that aspirin withdrawal in coronary patients may represent a real risk for the occurrence of a new coronary event . Many cases involved late uncoated-stent thrombosis . Assessment of the exact incidence of coronary recurrences after aspirin withdrawal will need prospect i ve studies Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews |
2,377 | 23,235,630 | We found moderate- quality evidence that CBT did not significantly reduce time until partial RTW and low- quality evidence that it did not significantly reduce time to full RTW compared with no treatment .
Moderate- quality evidence showed that PST significantly enhanced partial RTW at one-year follow-up compared to non- guideline based care but did not significantly enhance time to full RTW at one-year follow-up . | BACKGROUND Adjustment disorders are a frequent cause of sick leave and various interventions have been developed to expedite the return to work ( RTW ) of individuals on sick leave due to adjustment disorders .
OBJECTIVES To assess the effects of interventions facilitating RTW for workers with acute or chronic adjustment disorders . | Introduction Return to work ( RTW ) of employees on sick leave for common mental disorders may require a multidisciplinary approach . This article aims to assess time to RTW after a psychiatric consultation providing treatment advice to the occupational physician ( OP ) for employees on sick leave for common mental disorders in the occupational health ( OH ) setting , compared to care as usual ( CAU ) . Methods Cluster r and omized clinical trial evaluating patients of 12 OPs receiving consultation by a psychiatrist , compared to CAU delivered by 12 OPs in the control group . 60 patients suffering from common mental disorders and ≥ six weeks sicklisted were included . Follow up three and six months after inclusion . Primary outcome measure was time to RTW . Intention- to-treat multilevel analysis and a survival analysis were performed to evaluate time to RTW in both groups . Results In CAU , referral was the main intervention . Both groups improved in terms of symptom severity and quality of life , but time to RTW was significantly shorter in the psychiatric consultation group . At three months follow up , 58 % of the psychiatric consultation group had full RTW versus 44 % of the control group , a significant finding ( P = 0.0093 ) . Survival analysis showed 68 days earlier RTW after intervention in the psychiatric consultation group ( P = 0.078 ) compared to CAU . Conclusion Psychiatric consultation for employees on sick leave in the OH setting improves time to RTW in patients with common mental disorders as compared to CAU . In further research , focus should be on early intervention in patients with common mental disorders on short sick leave duration . Psychiatric consultation might be particularly promising for improvement of RTW in those patients . Trial registration number IS RCT N : Background To reduce the duration of sick leave and loss of productivity due to common mental disorders ( CMDs ) , we developed a return-to-work programme to be provided by occupational physicians ( OPs ) based on the principles of exposure in vivo ( RTW-E programme ) . This study evaluates this programme 's effectiveness and cost-effectiveness by comparing it with care as usual ( CAU ) . The three research questions we have are : 1 ) Is an RTW-E programme more effective in reducing the sick leave of employees with common mental disorders , compared with care as usual ? 2 ) Is an RTW-E programme more effective in reducing sick leave for employees with anxiety disorders compared with employees with other common mental disorders ? 3 ) From a societal perspective , is an RTW-E programme cost-effective compared with care as usual ? Methods / design This study was design ed as a pragmatic cluster-r and omized controlled trial with a one-year follow-up and r and omization on the level of OPs . We aim ed for 60 OPs in order to include 200 patients . Patients in the intervention group received the RTW-E programme . Patients in the control group received care as usual . Eligible patients had been on sick leave due to common mental disorders for at least two weeks and no longer than eight weeks . As primary outcome measures , we calculated the time until full return to work and the duration of sick leave . Secondary outcome measures were time until partial return to work , prevalence rate of sick leave at 3 , 6 , 9 , and 12 months ' follow-up , and scores of symptoms of distress , anxiety , depression , somatization , and fatigue ; work capacity ; perceived working conditions ; self-efficacy for return to work ; coping behaviour ; avoidance behaviour ; patient satisfaction ; and work adaptations . As process measures , we used indices of compliance with the intervention in the intervention group and employee-supervisor communication in both groups . Economic costs were calculated from a societal perspective . The total costs consisted of the costs of consuming health care , costs of production loss due to sick leave and reduced productivity , and out-of-pocket costs of patients for travelling to their OP . Discussion The results will be published in 2009 . The strengths and weaknesses of the study protocol are discussed . Trial registration IS RCT OBJECTIVE High levels of work-related stress are associated with increased absenteeism from work and reduced work ability . In this study , we investigated the effects of a stress management intervention on absenteeism and return to work . METHODS We r and omized 102 participants into either the intervention or wait-list control ( WLC ) group . The intervention group received the intervention in weeks 1 - 16 from baseline , and the WLC group received the intervention in weeks 17 - 32 . Self-reported data on absenteeism ( number of days full- or part-time absent from work within the previous three months ) were obtained at 16 , 32 , and 48 weeks follow-up . Register-based data on long-term absence from work were drawn from the Danish public transfer payments ( DREAM ) data base from baseline and 48 weeks onwards . The DREAM data base contains weekly information on long-term sickness absence compensation . The threshold to enter DREAM is sick leave for two consecutive weeks . RESULTS At follow-up in week 16 , self-reported absenteeism in the intervention group [ median 11 days ( range 3 - 25 ) ] was lower ( P=0.02 ) than in the WLC group [ median 45 days ( range 19 - 60 ) ] , corresponding to a 29 % [ 95 % confidence interval ( 95 % CI ) 5 - 52 ] reduction . On register-based data ( cumulated weeks in DREAM , weeks 1 - 16 ) , the intervention group median [ 6 weeks ( range 0 - 11 ) ] was lower than that of the WLC group [ median 12 weeks ( range 8 - 16 ) ] , though not significantly ( P=0.06 ) , corresponding to a 21 % ( 95 % CI 0 - 42 ) reduction . For return to work , a hazard ratio of 1.58 ( 95 % CI 0.89 - 2.81 ) favoring the intervention group was found ( P=0.12 ) . CONCLUSIONS The intervention reduces self-reported absenteeism from work . A similar trend was found from register-based records . No conclusive evidence was found for return to work Background Considering the high costs of sick leave and the consequences of sick leave for employees , an early return-to-work of employees with mental disorders is very important . Therefore , a workplace intervention is developed based on a successful return-to-work intervention for employees with low back pain . The objective of this paper is to present the design of a r and omized controlled trial evaluating the cost-effectiveness of the workplace intervention compared with usual care for sick-listed employees with common mental disorders . Methods The study is design ed as a r and omized controlled trial with a follow-up of one year . Employees eligible for this study are on sick leave for 2 to 8 weeks with common mental disorders . The workplace intervention will be compared with usual care . The workplace intervention is a stepwise approach that aims to reach consensus about a return-to-work plan by active participation and strong commitment of both the sick-listed employee and the supervisor . Outcomes will be assessed at baseline , 3 , 6 , 9 and 12 months . The primary outcome of this study is lasting return-to-work , which will be acquired from continuous registration systems of the companies after the follow-up . Secondary outcomes are total number of days of sick leave during the follow-up , severity of common mental disorders , coping style , job content , and attitude , social influence , and self-efficacy determinants . Cost-effectiveness will be evaluated from the societal perspective . A process evaluation will also be conducted . Discussion Return-to-work is difficult to discuss in the workplace for sick-listed employees with mental disorders and their supervisors . Therefore , this intervention offers a unique opportunity for the sick-listed employee and the supervisor to discuss barriers for return-to-work . Results of this study will possibly contribute to improvement of disability management for sick-listed employees with common mental disorders . Results will become available in 2009.Trial registration IS RCT Background Workplace mental health promotion ( WMHP ) aims to prevent and effectively manage the social and economic costs of common mental illnesses such as depression . The mental health of managers and employees within small-medium enterprises ( SMEs ) is a neglected sector in occupational health research and practice , despite the fact that this sector is the most common work setting in most economies . The availability and propensity of SME staff to attend face-to-face training/therapy or workshop style interventions often seen in corporate or public sector work setting s is a widely recognised problem . The ' Business in Mind ' program employs a DVD mode of delivery that is convenient for SME managers , particularly those operating in regional and remote areas where internet delivery may not be optimal . The objective of the intervention program is to improve the mental health of SME managers , and examine whether employees of managers ' whose mental health improves , report positive change in their psychosocial work environment . The mechanisms via which we aim to improve managers ' mental health are through the development of their psychological capital ( a higher order construct comprised of hope , self efficacy , resilience and optimism ) and their skills and capacities for coping with work stress . Methods / Design The effectiveness of two versions of the program ( self administered and telephone facilitated ) will be assessed using a r and omised trial with an active control condition ( psychoeducation only ) . We aim to recruit a minimum of 249 managers and a sample of their employees . This design allows for 83 managers per group , as power analyses showed that this number would allow for attrition of 20 % and still enable detection of an effect size of 0.5 . The intervention will be implemented over a three month period and postal surveys will assess managers and employees in each group at baseline , intervention completion , and at 6 month follow up . The intervention groups ( managers only ) will also be assessed at 12 and 24 month follow-up to examine maintenance of effects . Primary outcomes are managers ' levels of psychological capital ( hope , resilience , self-efficacy and optimism ) , coping strategies , anxiety and depression symptoms , self-reported health , job satisfaction and job tension . Secondary outcomes are participating managers subordinates ' perceptions of manager support , relational justice , emotional climate and job tension . In order to provide an economic evaluation of the intervention , both employees and manager rates of absenteeism and presenteeism will also be assessed . Discussion The intervention being trialled is expected to improve both primary and secondary outcomes . If proven efficacious , the intervention could be disseminated to reach a much larger proportion of the business community . Trial registration Current controlled trials IS RCT N Background Major depressive disorder is among the medical conditions with the highest negative impact on work outcome . However , little is known regarding evidence -based interventions targeting the improvement of work outcomes in depressed employees . In this paper , the design of a r and omized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression . This occupational intervention is based on an earlier intervention , which was design ed and proven effective by our research group , and is the only intervention to date that specifically targets work outcome in depressed employees . Methods / Design In a two-arm r and omized controlled trial , a total of 117 participants are r and omized to either ' care as usual ' or ' care as usual ' with the addition of occupational therapy . Patients included in the study are employees who are absent from work due to depression for at least 25 % of their contract hours , and who have a possibility of returning to their own or a new job . The occupational intervention consists of six individual sessions , eight group sessions and a work-place visit over a 16-week period . By increasing exposure to the working environment , and by stimulating communication between employer and employee , the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies . Assessment s take place at baseline , and at 6 , 12 , and 18-month follow-ups . Primary outcome measure is work participation ( hours of absenteeism and time until work resumption ) . Secondary outcome measures are work functioning , symptomatology , health-related quality of life , and neurocognitive functioning . In addition , cost-effectiveness is evaluated from a societal perspective . Finally , mechanisms of change ( intermediate outcomes ) and potential patient-treatment matching variables are investigated . Discussion This study hopes to provide valuable knowledge regarding an intervention to treat depression , one of the most common and debilitating diseases of our time . If our intervention is proven ( cost- ) effective , the personal , economic , and health benefits for both patients and employers are far-reaching . Trial registration Background Common mental disorders , such as depression , anxiety disorder , and adjustment disorder , have emerged as a major public and occupational health problem in many countries . These disorders can have severe consequences such as absenteeism and work disability . Different interventions have been developed to improve the return-to-work of employees with common mental disorders , but still a large proportion of employees experiences health and work problems after their return-to-work . For this reason , the SHARP-at work intervention is developed to prevent a relapse of sickness absence among employees who have returned to work after a period of sickness absence because of common mental disorders . We aim to evaluate the effectiveness , cost-benefit and process of the intervention compared to care as usual . Methods / Design The study is design ed as a cluster-r and omised controlled trial with r and omisation at the level of the occupational physician . Employees who have returned to work after a period of sickness absence because of a common mental disorder are included in the study . Employees in the intervention group will receive the SHARP-at work intervention . The intervention focusses on active guidance of employees by occupational physicians during the first weeks of work after sickness absence . Employees in the control group will receive care as usual . Outcomes will be assessed at baseline and at 3 , 6 , and 12 months follow-up . The primary outcome is cumulative recurrent sickness absence days . Secondary outcome measures are mental health , work functioning , and coping . Adherence to the protocol , communication between stakeholders , and satisfaction with the treatment are the process measures assessed in both study groups . Cost-benefit is calculated from a societal perspective . Finally , prognostic factors for a relapse of sickness absence are investigated . Discussion This study goes beyond return-to-work by focussing on the prevention of recurrent sickness absence . The study incorporates not only outcomes on sickness absence and mental health but also on health-related work functioning . The results of this study can contribute to a further development of practice guidelines and the promotion of sustainable work participation . Trial registration Background : The impact of depression on the workplace has been widely observed in studies examining absenteeism and reduced productivity during days at work . However , there is little scientific evidence about whether depression interventions are cost-beneficial to employers . Objective : We construct a cost – benefit analysis of depression treatment under different workplace assumptions better reflecting the nature of employment . Research Design : Data from a r and omized controlled trial in which employed primary care patients with depression were treated in practice s r and omly assigned to an enhanced treatment intervention or usual care were used to construct a cost – benefit model from an employer perspective under different assumptions regarding employment . Subjects : A national sample of 198 workers employed in a range of positions by companies was studied . Measures : Benefits included self-reported productivity and absenteeism ; costs included intervention and treatment costs . Net benefit was calculated under different scenarios and return on investment ( ROI ) is derived . Results : Enhanced depression treatment result ed in an average net benefit to the employer of $ 30 per participating worker in Year 1 of the intervention and $ 257 per participating worker in Year 2 , for an estimated ROI during the 2-year period of 302 % . ROI increased in firms that rely on team production , hire more costly substitute labor , or realize penalties for output shortfalls . ROI decreased in firms that have a large fraction of employees with dependent coverage and experience high turnover rates . Results also are sensitive to how subjectively reported productivity is valued . Conclusion : Many employers will receive a potentially significant ROI from depression treatment models that improve absenteeism and productivity at work BACKGROUND Fatigue is a common complaint that may lead to long-term sick leave and work disability . AIMS To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained , persistent fatigue among employees . METHOD A r and omised controlled trial , using a pre-r and omisation design in primary care , investigated 151 employees on sick leave with fatigue . Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner ; those in the control group were offered no treatment . Main outcome measures ( fatigue severity , self-reported absenteeism , registered absenteeism and clinical recovery ) were assessed at 4 months , 8 months and 12 months . RESULTS At baseline , 44 % of the patients already met research criteria for chronic fatigue syndrome . There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point . CONCLUSIONS Cognitive-behavioural therapy by general practitioners for unexplained , persistent fatigue did not prove to be an effective intervention . Since these doctors were unable to deliver this therapy effectively under ideal circumstances , it is unlikely that doctors in routine practice would be more successful in doing so BACKGROUND A course in coping with depression was reported to have documented effects in terms of shortening periods of depression . An economic evaluation of the course was conducted . MATERIAL S AND METHODS The estimate of medical effect derives from a r and omized controlled trial in 155 subjects with depression . On average subjects in the intervention group improved 3 - 4 points more on the Beck Depression Inventory than subjects in the control group . A value estimate is provided for this effect given what is known about the weight that society places on severity of illness and effect of treatment when prioritising among patient groups . The value estimate is compared with the costs of the course . RESULTS AND INTERPRETATION It is estimated that if 200 people take the course , the improvements in quality of life for all these people taken together may be regarded as equally valuable and worthy of priority as an intervention that provides an extra life year to one person . The cost of giving the course to 200 people is estimated at USD 45,000 - 60,000 . This is within the limits of what society is generally willing to pay in order to gain life years . Because of possible reductions in sick leave , societal net costs may be modest CONTEXT Panic disorder and generalized anxiety disorder are prevalent in primary care , associated with poor functional outcomes , and are often unrecognized and ineffectively treated by primary care physicians . OBJECTIVE To examine whether telephone-based collaborative care for panic and generalized anxiety disorders improves clinical and functional outcomes more than the usual care provided by primary care physicians . DESIGN R and omized controlled trial . SETTING Four Pittsburgh area primary care practice s linked by a common electronic medical record system . Patients A total of 191 adults aged 18 to 64 years with panic and /or generalized anxiety disorder who were recruited from July 2000 to April 2002 . Intervention Patients were r and omly assigned to a telephone-based care management intervention ( n = 116 ) or to notification alone of the anxiety disorder to patients and their physicians ( usual care , n = 75 ) . The intervention involved non-mental health professionals who provided patients with psychoeducation , assessed preferences for guideline -based care , monitored treatment responses , and informed physicians of their patients ' care preferences and progress via an electronic medical record system under the direction of study investigators . MAIN OUTCOME MEASURES Independent blinded assessment s of anxiety and depressive symptoms , mental health-related quality of life , and employment status at baseline , 2- , 4- , 8- , and 12-month follow-up . RESULTS At 12-month follow-up , intervention patients reported reduced anxiety ( effect size [ ES ] , 0.33 - 0.38 ; 95 % confidence interval [ CI ] , 0.04 to 0.67 ; P</=.02 ) and depressive symptoms ( ES , 0.35 ; 95 % CI , 0.25 - 0.46 ; P = .03 ) ; improved mental health-related quality of life ( ES , 0.39 ; 95 % CI , 0.10 to 0.68 ; P = .01 ) ; and larger improvements relative to baseline in hours worked per week ( 5.7 ; 95 % CI , 0.1 to 11.3 ; P = .05 ) and fewer work days absent in the past month ( -2.6 ; 95 % CI , - 4.8 to -0.3 ; P = .03 ) than usual care patients . If working at baseline , more intervention patients than usual care patients remained working at 12-month follow-up ( 94 % vs 79 % [ 15 % absolute difference , 0.7%-28.6 % ] ; P = .04 ) . CONCLUSIONS Telephone-based collaborative care for panic disorder and generalized anxiety disorder is more effective than usual care at improving anxiety symptoms , health-related quality of life , and work-related outcomes Background The main aims of this paper are to describe the setting and design of a Minimal Intervention in general practice for Stress-related mental disorders in patients on Sick leave ( MISS ) , as well as to ascertain the study complies with the requirements for a cluster r and omised controlled trial ( RCT ) . The potential adverse consequences of sick leave due to Stress-related Mental Disorders ( SMDs ) are extensive , but often not recognised . Since most people having SMDs with sick leave consult their general practitioner ( GP ) at an early stage , a tailored intervention given by GPs is justified . We provide a detailed description of the MISS ; that is more accurate assessment , education , advice and monitoring to treat SMDs in patients on sick leave . Our hypothesis is that the MISS will be more effective compared to the usual care , in reducing days of sick leave of these patients . Methods The design is a pragmatic RCT . R and omisation is at the level of GPs . They received the MISS-training versus no training , in order to compare the MISS vs. usual care at patient level . Enrolment of patients took place after screening in the source population , that comprised 20–60 year old primary care attendees . Inclusion criteria were : moderately elevated distress levels , having a paid job and sick leave for no longer than three months . There is a one year follow up . The primary outcome measure is lasting full return to work . Reduction of SMD- symptoms is one of the secondary outcome measures . Forty-six GPs and 433 patients agreed to participate . Discussion In our study design , attention is given to the practical application of the requirements for a pragmatic trial . The results of this cluster RCT will add to the evidence about treatment options in general practice for SMDs in patients on sick leave , and might contribute to a new and appropriate guideline . These results will be available at the end of 2006 BACKGROUND We set out to investigate whether community nurses could be trained in problem-solving therapy and , once trained , how effective they would be in treating emotional disorders in primary care . METHOD Seventy patients with an emotional disorder in primary care were r and omly allocated to receive either problem-solving therapy from a trained community nurse or treatment as usual from their general practitioner . Interview and self-rated assessment s of clinical and economic outcome were made pretreatment , at eight weeks and at 26 weeks after treatment . RESULTS There was no difference in clinical outcome between patients who received problem-solving treatment and patients who received the general practitioner 's usual treatment . However , patients who received problem-solving treatment had fewer disability days and fewer days off work . The health care cost of problem-solving was greater than that of the general practitioner 's usual treatment but this was more than offset by savings in the cost of days off work . CONCLUSIONS Problem-solving treatment can be given by trained community nurses . The clinical effectiveness and cost-benefit of the treatment will depend on the selection of appropriate patients Background Stress-related disorders are widespread and responsible for high societal costs e.g. sick leave payment and reduced productivity . The aim of this study was to evaluate the effect of an intervention program on return to work or labour market . Methods In a controlled interventional study design we compared 72 emotionally distressed patients , who received support during 2006 , with 89 control individuals who had also been sick listed for emotional distress . Intervention was provided by trained psychologists and social workers who were in continuous dialog with the patients , providing counselling e.g. on decisions concerning resumption of work , support to families , participation in meetings with the workplace . Basically , the controls and the intervention group share the same access to welfare benefits . The main outcome was time to return to labour market ( TTR ) . Results The baseline characteristics were similar in the two groups . There were no differences in the rate of resuming work between the two groups . About 80 % in both groups had returned to the labour market after one year . Conclusion An intervention program with psychological stress management and case management did not improve work capability compared to usual care . Work resumption as a single outcome probably is an insensitive parameter of intervention management quality , and should be supplemented by other data on different aspects of treatment AIM This paper is a report of a study to test the effect of participating in a reflecting peer-support group on self-reported health , burnout and on perceived changes in work conditions . BACKGROUND Stress-related conditions are one of the most common causes for long-term sick-leave . There is limited evidence for the effectiveness of person-directed interventions aim ed at reducing stress levels in healthcare workers . Prior research in the relationship between support and burnout show somewhat inconsistent results . METHOD A r and omized controlled trial with peer-support groups as the intervention was conducted with 660 healthcare workers scoring above the 75th percentile on the exhaustion dimension of the Oldenburg Burnout Inventory . One hundred and fifty-one ( 22.9 % ) agreed to participate . The intervention started in 2002 with 51 participants ( 96.1 % were women ) , 80 of whom constituted the control group . Potential differences in outcome measures 12 months after the intervention were compared using ancova , and data collected was completed in 2004 . Qualitative content analyses were used to analyse reported experiences from group participation . RESULTS Statistically significant intervention effects were found for general health , perceived quantitative dem and s at work , participation and development opportunities at work and in support at work . Seven categories of experiences from participating were identified : talking to others in a similar situation , knowledge , sense of belonging , self-confidence , structure , relief of symptoms and behavioural change . CONCLUSION Peer-support groups using a problem-based method could be a useful and comparatively inexpensive tool in alleviating work-related stress and burnout Objective .The objective of this work was to develop a psychometrically sound question naire for measuring the on-the-job impact of chronic health problems and /or treatment ( “ work limitations ” ) . Research Design .Three pilot studies ( focus groups , cognitive interviews , and an alternate forms test ) generated c and i date items , dimensions , and response scales . Two field trials tested the psychometric performance of the question naire ( studies 1 and 2 ) . To test recall error , study 1 subjects were r and omly assigned to 2 different question naire groups , a question naire with a 4-week reporting period completed once or a 2-week version completed twice . Responses were compared with data from concurrent work limitation diaries ( the gold st and ard ) . To test construct validity , we compared question naire scores of patients with those of healthy job-matched control subjects . Study 2 was a cross-sectional mail survey testing scale reliability and construct validity . Subjects . The study subjects were employed individuals ( 18–64 years of age ) from several chronic condition groups ( study 1 , n = 48 ; study 2 , n = 121 ) and , in study 1 , 17 healthy matched control subjects . Measures . Study 1 included the assigned question naires and weekly diaries . Study 2 included the new question naire , SF-36 , and work productivity loss items . Results .In study 1 , question naire responses were consistent with diary data but were most highly correlated with the most recent week . Patients had significantly higher ( worse ) limitation scores than control subjects . In study 2 , 4 scales from a 25-item question naire achieved Cronbach alphas of ≥0.90 and correlated with health status and self-reported work productivity in the hypothesized manner ( P ≤0.05 ) . Conclusions .With 25 items , 4 dimensions ( limitations h and ling time , physical , mental-interpersonal , and output dem and s ) , and a 2-week reporting period , the Work Limitations Question naire demonstrated high reliability and validity Objective : Mental health problems often affect functioning to such an extent that they result in sick leave . The worldwide reported prevalence of mental health problems in the working population is 10%–18 % . In developed countries , mental health problems are one of the main grounds for receiving disability benefits . In up to 90 % of cases the cause is stress-related , and health-care utilisation is mainly restricted to primary care . The aim of this study was to assess the effectiveness of our Minimal Intervention for Stress-related mental disorders with Sick leave ( MISS ) in primary care , which is intended to reduce sick leave and prevent chronicity of symptoms . Design : Cluster-r and omised controlled educational trial . Setting : Primary health-care practice s in the Amsterdam area , The Netherl and s. Participants : A total of 433 patients ( MISS n = 227 , usual care [ UC ] n = 206 ) with sick leave and self-reported elevated level of distress . Interventions : Forty-six primary care physicians were r and omised to either receive training in the MISS or to provide UC . Eligible patients were screened by mail . Outcome Measures : The primary outcome measure was duration of sick leave until lasting full return to work . The secondary outcomes were levels of self-reported distress , depression , anxiety , and somatisation . Results : No superior effect of the MISS was found on duration of sick leave ( hazard ratio 1.06 , 95 % confidence interval 0.87–1.29 ) nor on severity of self-reported symptoms . Conclusions : We found no evidence that the MISS is more effective than UC in our study sample of distressed patients . Continuing research should focus on the potential beneficial effects of the MISS ; we need to investigate which elements of the intervention might be useful and which elements should be adjusted to make the MISS effective ABSTRACT Background : Improving health-related quality of life ( HRQoL ) should be a treatment goal for patients with Generalised Anxiety Disorder ( GAD ) . Objectives : To assess the impact of treatment with escitalopram on HRQoL as well as the effect of relapse on HRQoL and work productivity . Methods : This study was conducted alongside a double-blind , placebo-controlled , relapse prevention multinational clinical trial . Relapse was defined as a Hamilton Anxiety Scale ( HAMA ) ≥ 15 . Treatment responders ( HAMA ≤ 10 ) after 12 weeks of open-label treatment ( 10 mg/day escitalopram for Week 1 followed by 20 mg/day thereafter ) were included . The study data set comprised patients ( n = 329 ) from French , Canadian , German and Swedish centres . HRQoL was assessed using the SF-36 scale , and data on sick leave and on-the-job productivity as measured by the Work Limitation Question naire and the work efficacy and work satisfaction visual analogue scales ( VAS ) scales were collected at baseline , r and omization ( Week 12 ) , Weeks 36 , 60 and at last assessment . For future health economic analysis , quality adjusted life years were calculated from the SF-36 results . Results : At baseline , GAD patients reported significantly impaired quality of life compared with the general population . During the 12-week open-label treatment period , treatment responders reported significant improvements in HRQoL on all dimensions of the SF-36 ( p < 0.001 ) and on-the-job productivity ( p < 0.001 ) , whereas sick leave decreased but did not reach statistical significance . After r and omization , relapsed patients reported significantly lower QoL than non-relapsed patients on all 4 SF-36 mental health dimensions ( p < 0.001 ) . Relapsed patients reported slightly lower on-the-job productivity than non-relapsed patients and scored lower on the work efficacy and work satisfaction VAS scales . Conclusion : GAD adversely affects patient functioning and daily life . Short-term treatment with escitalopram reverses this impairment to population norms . GAD relapse is associated with a deterioration of HRQoL and work productivity Background Major depressive disorder ( MDD ) has major consequences for both patients and society , particularly in terms of needlessly long sick leave and reduced functioning . Although evidence -based treatments for MDD are available , they show disappointing results when implemented in daily practice . A focus on work is also lacking in the treatment of depressive disorder as well as communication of general practitioners ( GPs ) and other health care professionals with occupational physicians ( OPs ) . The OP may play a more important role in the recovery of patients with MDD . Purpose of the present study is to tackle these obstacles by applying a collaborative care model , which has proven to be effective in the USA , with a focus on return to work ( RTW ) . From a societal perspective , the (cost)effectiveness of this collaborative care treatment , as a way of transmural care , will be evaluated in depressed patients on sick leave in the occupational health setting . Methods / Design A r and omised controlled trial in which the treatment of MDD in the occupational health setting will be evaluated in the Netherl and s. A transmural collaborative care model , including Problem Solving Treatment ( PST ) , a workplace intervention , antidepressant medication and manual guided self-help will be compared with care as usual ( CAU ) . 126 Patients with MDD on sick leave between 4 and 12 weeks will be included in the study . Care in the intervention group will be provided by a multidisciplinary team of a trained OP-care manager and a consultant psychiatrist . The treatment is separated from the sickness certification . Data will be collected by means of question naires at baseline and at 3 , 6 , 9 and 12 months after baseline . Primary outcome measure is reduction of depressive symptoms , secondary outcome measure is time to RTW , tertiary outcome measure is the cost effectiveness . Discussion The high burden of MDD and the high level of sickness absence among people with MDD contribute to the relevance of this study . The intervention is an innovative approach , with trained OPs in a new role as care managers in the treatment of MDD . If this intervention proves to be cost-effective , implementation will be very relevant for individual patients as well as for society . Trial registration IS RCT BACKGROUND Sickness absence due to mental health problems ( MHPs ) is increasing in several European countries . However , little is known about return to work ( RTW ) for employees with MHPs . This prospect i ve study aim ed to identify predictors for RTW in employees sick-listed with MHPs . METHODS Employees were recruited when applying for sickness benefit due to MHPs from the Municipality of Copenhagen ( n = 644 ) . Information about age , gender , occupation , self-reported RTW expectancy , self-reported reason for absence and prior absence with MHPs was retrieved from application forms for sickness benefit . Each participant was followed-up in the National Register for Social Transfer Payments for a maximum period of 52 weeks to estimate time to RTW . Hazard ratios for RTW with 95 % confidence intervals were calculated using Cox proportional regression analyses . RESULTS Employees sick-listed with self-reported stress/burnout returned to work faster than those with self-reported depression ( HR = 0.76 ) , and other MHPs ( HR = 0.56 ) . A positive RTW expectancy of the sick-listed person ( HR = 1.27 ) and no prior absence with MHPs ( HR = 1.29 ) were associated with a shorter time to RTW . CONCLUSION Sickness absence due to self-reported stress/burnout , a positive RTW expectancy and no prior absence with MHPs predicted a shorter time to RTW among Danish employees sick listed with MHPs . Findings could help social insurance officers and other rehabilitation professionals to identify groups at high risk for prolonged absence Abstract Objective : To test whether a disclosure intervention improves subjective health and reduces medical consumption and sick leave in somatising patients in general practice . Design : Non-blind r and omised controlled trial . Setting : 10 general practice s in the Netherl and s. Participants : 161 patients who frequently attended general practice with somatising symptoms . Intervention : Patients in the intervention group were visited two to three times and invited to disclose emotionally important events in their life . Control patients received normal care from their general practitioners . Main outcome measures : Use of medical services ( drugs and healthcare visits ) , subjective health , and sick leave assessed by self completion question naires after 6 , 12 , and 24 months . Results : Of the 161 patients , 137 completed the trial ( 85 % ) . Both groups were comparable at baseline . The intervention had no effect on the main outcome measures at any point . Intervention patients made one more visit to health care ( 95 % confidence interval −4 to 6 ) ; the use of medicines did not change in both groups ( −1 to 1 ) ; subjective health improved 3.6 points more in the control group ( −11.2 to 4.3 ) ; and disclosure patients were on sick leave one more week ( −1 to 3 ) . Patients often had a depression or anxiety disorder for which they were not receiving adequate care . Conclusion : Although the intervention was well received by patients and doctors , disclosure had no effect on the health of somatising patients in general practice . What is already known on this topic Up to 5 % of patients in general practice attend frequently with somatising symptoms Emotional expression techniques have been shown to have favourable effects on subjective health , visits to the doctor , and symptoms in healthy people What this study adds A disclosure intervention does not improve somatisation in primary care About 45 % of patients had an anxiety or depressive disorder , which was often OBJECTIVE The aim of this study was to examine the adherence of occupational physicians ( OP ) to the Dutch guideline on the management of common mental health problems and its effect on return to work as part of the process evaluation of a trial comparing adherence to the guideline to care as usual . The first hypothesis was that guideline adherence among the " guideline group " will be higher compared to the " usual care group " . The second hypothesis was that better guideline adherence by the occupational physician will be associated with earlier return to work . METHODS In a r and omized controlled trial , five participating OP had to provide care based on the Dutch guideline to 240 police workers with common mental health problems ( the " guideline group " ) . The same OP had to provide usual care to the participants in the control group ( the " usual care " group ) , including minimal involvement and easy access to a psychologist . In evaluating the process , we assessed guideline adherence via an audit of medical files , using 20 guideline -based performance indicators . Mean rates of guideline adherence were related to the duration until first and full return to work , using a Cox proportional hazards model . RESULTS The mean rate of the sum score of guideline adherence was 10 in a range of 0 - 20 [ st and ard deviation ( SD ) 1.8 ] and did not significantly differ between the intervention and control group . Mean better guideline adherence showed a statistically significant association with a shorter time to first and full return to work [ hazard ratio 1.1 ; 95 % confidence interval ( 95 % CI ) 1.0 - 1.2 ] , which was explained by keeping more regular contact with the worker and the work system and better monitoring of stagnation or return to work . CONCLUSIONS No contrast in guideline adherence was found between guideline -based versus usual care . This can be explained by contamination between the guideline and usual care group . Even though guideline adherence was only average , better adherence predicted earlier return to work . Guidelines for management of common mental health problems and return to work should focus on regular contact with the worker and the work organisation Work-related stress is widespread and can lead to long-term absenteeism and work disability . Cognitive-behavioral treatment ( CBT ) has demonstrated effectiveness in treating psychopathology but has only rarely been tested in clinical sample s with work-related stress . A r and omized controlled trial was conducted to investigate the efficacy of CBT-based stress management training ( SMT ) . Eighty-two patients on sickness leave with work-related stress were r and omly assigned to ( a ) individual SMT , ( b ) group SMT , or ( c ) care as usual ( CAU ) . The SMT comprised 12 sessions conducted by a psychologist . Complaints of burnout and distress were measured at baseline , and at 4 , 7 , and 10 months . Absenteeism was measured during the whole research period . Across treatment conditions , complaints and sickness absence reduced considerably between baseline and 4 months . Thereafter , complaints remained approximately stable , whereas sickness absence further reduced . Hardly any significant group difference emerged , and no consistent pattern could be discerned in favor of any treatment condition . In subgroups with low depressive complaints , though , individual SMT result ed in larger reductions of some complaints than CAU . In conclusion , this study adds to the evidence that CBT-based interventions as currently practice d are not successful in treating patients with clinical levels of work-related stress Background Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years . In the current study we assess the feasibility and effectiveness of offering a voluntary , solution-focused follow-up to sick-listed employees . Methods Employees on long-term sick leave due to psychological problems or muscle skeletal pain were r and omly allocated to be offered a solution-focused follow-up ( n = 122 ) or " treatment as usual " ( n = 106 ) . The intervention was integrated within 2 social security offices ' regular follow-up . The intervention group was informed about the offer with letters , telephone calls and information meetings . Feasibility was measured by rate of uptake to the intervention , and effectiveness by number of days on sick leave . Results In general , few were reached with the different information elements . While the letter was sent to all , only 31 % were reached by telephone and 15 % attended the information meetings . Thirteen employees ( 11.5 % ) in the intervention group participated in the solution-focused follow-up . Intention to treat analysis showed no difference in mean length of sick leave between the intervention group ( 217 days ) and the control group ( 189 days ) ( p = 0,101 ) . Conclusion Even if the information strategy might be improved , it is not likely that a voluntary solution-focused follow-up offered by the social security offices would result in measurable reduction in length of sick leave on a population level . However , the efficacy of a solution-focused follow-up for the persons reporting a need for this approach should be further investigated The Mental Health Action Checklist for a Better Workplace Environment ( MHACL ) is a tool for a worker participatory approach to improve work environments for worker mental health . The present study investigated the effects of an organizational intervention using the MHACL on reducing job stressors and the psychological distress of workers of a manufacturing enterprise in Japan with a controlled study design . Nine of 45 departments participated in a work environment improvement program , including planning workshops , implementation and monitoring , between July and December 2005 ( intervention group , n=321 ) . The remaining 36 departments served as the control group ( n=750 ) . Outcomes ( job stressors , worksite support , psychological distress , etc . ) , measured using the Brief Job Stress Question naire , as well as sick leave days taken from the company record , were recorded before and six months after the program for both groups . Among women , skill underutilization , supervisor and coworker support , psychological distress , and job satisfaction changed more favorably in the intervention group than in the control group ( p<0.05 ) . No significant favorable effect of the program was observed among men . Improvements in the outcomes were more prominent among departments with a 50 % or higher rate of worker participation in the planning workshops and among departments with a 50 % or higher rate of implemented vs. planned actions . A worker participatory organizational intervention using the MHACL seems effective for promoting mental health among Japanese white-collar women BACKGROUND Sickness absence often occurs in patients with emotional distress or minor mental disorders . In several European countries , these patients are over-represented among those receiving illness benefits , and interventions are needed . The aim of this study was to evaluate the cost-effectiveness of an intervention conducted by social workers , design ed to reduce sick leave duration in patients absent from work owing to emotional distress or minor mental disorders . METHODS In this R and omized Controlled Trial , patients were recruited by GPs . The intervention group ( N = 98 ) received an activating , structured treatment by social workers , the control group ( N = 96 ) received routine GP care . Sick leave duration , clinical symptoms , and medical consumption ( consumption of medical staffs ' time as well as consumption of drugs ) were measured at baseline and 3 , 6 , and 18 months later . RESULTS Neither for sick leave duration nor for clinical improvement over time were significant differences found between the groups . Also the associated costs were not significantly lower in the intervention group . CONCLUSIONS Compared with usual GP care , the activating social work intervention was not superior in reducing sick leave duration , improving clinical symptoms , and decreasing medical consumption . It was also not cost-effective compared with GP routine care in the treatment of minor mental disorders . Therefore , further implementation of the intervention is not justified . Potentially , programmes aim ed at reducing sick leave duration in patients with minor mental disorders carried out closer to the workplace ( e.g. by occupational physicians ) are more successful than programmes in primary care Background Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years . In the current study we assess the efficacy of a solution-focused follow-up for sick-listed employees . Methods Employees on long-term sick leave due to psychological problems or muscle skeletal pain ( n = 703 ) were invited to participate in the project . Following self-recruitment , 103 were r and omly allocated to receive solution-focused follow-up ( n = 53 ) or " treatment as usual " ( n = 50 ) . The intervention was integrated within the regular follow up of six social security offices and organised as eight weekly solution focused work sessions . Effectiveness was measured by rate of return to work and health related quality of life ( SF-36 ) . Results Intention to treat analysis showed no significant differences between the two groups for any of the outcome measures . Secondary analysis , comparing those who attended at least 50 % of the sessions with the control group revealed a significant difference in favour of the active intervention group in the SF-36 subscale of mental health ( Effect Size 0.56 , p = 0.05 ) . When comparing the subgroup of participants with psychological problems there was a significant difference in mental health in favour of the intervention group ( Effect Size 0.71 , p = 0.041 ) . Conclusion A voluntary solution-focused intervention offered by social-security offices is no more effective than regular follow up for employees on long-term sick leave due to psychological problems or muscle skeletal pain Objectives To evaluate the cost effectiveness , cost utility and cost benefit of a workplace intervention compared with usual care for sick-listed employees with distress . Methods An economic evaluation was conducted alongside a r and omised controlled trial . Employees with distress and who were sick-listed for 2–8 weeks were r and omised to a workplace intervention ( n=73 ) or to usual care ( n=72 ) . The workplace intervention is a stepwise process involving the sick-listed employee and their supervisor , aim ed at formulating a consensus-based plan for return to work ( RTW ) . The effect outcomes were lasting RTW and quality -adjusted life years ( QALYs ) . Healthcare utilisation was measured over 12 months . Cost effectiveness analyses ( CEA ) and cost utility analyses ( CUA ) were conducted from the societal perspective and cost benefit analyses ( CBA ) from the employer perspective . Bootstrapping techniques were used to estimate cost and effect differences , related CIs , and cost effectiveness and cost utility ratios . Cost effectiveness planes were presented and subgroup analyses were performed . Results CEA and CUA revealed no statistically significant differences in lasting RTW , QALYs or costs . The CBA indicated a statistically significant higher cost of occupational health services in the workplace intervention group . The workplace intervention was not cost effective according to the CEA , CUA and CBA . Conclusions Widespread implementation of the workplace intervention for sick-listed employees with distress is not recommended because there was no economic benefit compared with usual care . Future trials should confirm if the workplace intervention is cost effective for the subgroup employees who intended to return to work despite symptoms . This trial has been registered at the Dutch National Trial Register IS RCT N92307123 Objective : To assess the effectiveness of a preventive coaching intervention on sickness absence due to psychosocial health complaints and on general well being of employees . Methods : Employees at risk for sickness absence were identified and r and omized . The intervention group received the preventive coaching program ; the control group received usual care . Primary outcome measure of the trial is sickness absence due to psychosocial health complaints ; secondary outcome measures are related to general well being , such as psychological distress , fatigue , and coping . Results : No effect of coaching on self-reported sickness absence due to psychosocial health complaints was found . The intervention group reported statistically significant improved health , declined psychological distress , less burnout , less need for recovery , and an increased satisfaction with life . Conclusions : This study shows that the coaching intervention primarily has an effect on general well being of employees Background Mental health problems often lead to prolonged sick leave . In primary care , the usual approach towards these patients was the advice to take rest and not return to work before all complaints had disappeared . When complaints persist , these patients are often referred to psychologists from primary and specialized secondary care . As an alternative , ways have been sought to activate the Dutch occupational physician ( OP ) in primary care . Early 2000 , the Dutch Association of Occupational Physicians ( NVAB ) published a guideline concerning the management by OPs of employees with mental health problems . The guideline received positive reactions from employees , employers and Dutch OPs . This manuscript describes the design of a study , which aims to assess the effects of the guideline , compared with usual care . Methods / Design In a r and omized controlled trial ( RCT ) , subjects in the intervention group were treated according to the guideline . The control group received usual care , with minimal involvement of the OP and easy access to a psychologist . Subjects were recruited from two Dutch police departments . The primary outcomes of the study are return to work and treatment satisfaction by the employee , employer , and OP . A secondary outcome is cost-effectiveness of the intervention , compared with usual care . Furthermore , prognostic measures are taken into account as potential confounders . A process evaluation will be done by means of performance indicators , based on the guideline . Discussion In this pragmatic trial , effectiveness instead of efficacy is studied . We will evaluate what is possible in real clinical practice , rather than under ideal circumstances . Many requirements for a high quality trial are being met . Results of this study will contribute to treatment options in occupational health practice for employees on sick leave due to mental health problems . Additionally , they may contribute to new and better-suited guidelines and stepped care . Results will become available during 2007.Trial registration Current Controlled Trials IS RCT Objectives The aim of this study is to examine the role of coping styles in sickness absence . In line with findings that contrast the reactive – passive focused strategies , problem-solving strategies are generally associated with positive results in terms of well-being and overall health outcomes ; our hypothesis is that such strategies are positively related to a low frequency of sickness absence and with short lengths ( total number of days absent ) and duration s ( mean duration per spell ) . Methods Using a prospect i ve design , employees ’ ( N = 3,628 ) responses on a self-report coping inventory are used to predict future registered sickness absence ( i.e. frequency , length , duration , and median time before the onset of a new sick leave period ) . Results and conclusions In accordance with our hypothesis , and after adjustment for potential confounders , employees with an active problem-solving coping strategy are less likely to drop out because of sickness absence in terms of frequency , length ( longer than 14 days ) , and duration ( more than 7 days ) of sickness absence . This positive effect is observed in the case of seeking social support only for the duration of sickness absence and in the case of palliative reaction only for the length and frequency of absence . In contrast , an avoidant coping style , representing a reactive – passive strategy , increases the likelihood of frequent absences significantly , as well as the length and duration of sickness absence . Expression of emotions , representing another reactive – passive strategy , has no effect on future sickness absenteeism . The median time before the onset of a new episode of absenteeism is significantly extended for active problem-solving and reduced for avoidance and for a palliative response . The results of the present study support the notion that problem-solving coping and reactive – passive strategies are inextricably connected to frequency , duration , length and onset of sickness absence . Especially , active problem-solving decreases the chance of future sickness absence Background R and omized trials demonstrate that depression care management can improve clinical and work outcomes sufficiently for selected employers to realize a return on investment . Employers can now purchase depression products that provide depression care management , defined as employee screening , education , monitoring , and clinician feedback for all depressed employees . We developed an intervention to encourage employers to purchase a depression product that offers the type , intensity , and duration of care management shown to improve clinical and work outcomes . Methods In a r and omized controlled trial conducted with 360 employers of 30 regional business coalitions , the research team proposes to compare the impact of a value-based marketing intervention to usual-care marketing on employer purchase of depression products . The study will also identify mediators and organizational-level moderators of intervention impact . Employers r and omized to the value-based condition receive a presentation encouraging them to purchase depression products scientifically shown to benefit the employee and the employer . Employers r and omized to the usual-care condition receive a presentation encouraging them to monitor and improve quality indicators for outpatient depression treatment . Because previous research demonstrates that the usual-care intervention will have little to no impact on employer purchasing , depression product purchasing rates in the usual-care condition capture vendor efforts to market depression products to employers in both conditions while the value-based intervention is being conducted . Employers in both conditions are also provided free technical assistance to undertake the actions each presentation encourages . The research team will use intent-to-treat models of all available data to evaluate intervention impact on the purchase of depression products using a cumulative incidence analysis of 12- and 24-month data . Discussion By addressing the ' value to whom ? ' question , the study advances knowledge about one of the most pivotal problems in the translation of evidence -based care to ' real world ' setting s : whether purchasers can be influenced to buy healthcare products on the basis of value and not exclusively on the basis of cost . If value-based marketing increases depression product purchase rates over usual care , this study will provide encouragement to market new healthcare products on the basis of the product 's value to the purchaser as well as the recipient of care . Trial Registration Clinical Trials Registration Number : In this comparative intervention study , 107 working individuals with above average levels of distress were r and omly assigned to one of three conditions : acceptance and commitment therapy ( ACT ; n = 37 ) ; stress inoculation training ( SIT ; n = 37 ) ; or a waitlist control group ( n = 33 ) . The interventions were delivered to small groups in the workplace via two half-day training sessions . ACT and SIT were found to be equally effective in reducing psychological distress across a three month assessment period . Mediation analysis indicated that the beneficial impact of ACT on mental health result ed from an increase in psychological flexibility rather than from a change in dysfunctional cognitive content . Contrary to hypothesis , a reduction in dysfunctional cognitions did not mediate change in the SIT condition . Results suggest that the worksite may offer a useful , yet underutilised , arena for testing cognitive-behavioural theories of change CONTEXT Although guideline -concordant depression treatment is clearly effective , treatment often falls short of evidence -based recommendations . Organized depression care programs significantly improve treatment quality , but employer purchasers have been slow to adopt these programs based on lack of evidence for cost-effectiveness from their perspective . OBJECTIVE To evaluate the effects of a depression outreach-treatment program on workplace outcomes , a concern to employers . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial involving 604 employees covered by a managed behavioral health plan were identified in a 2-stage screening process as having significant depression . Patient treatment allocation was concealed and assessment of depression severity and work performance at months 6 and 12 was blinded . Employees with lifetime bipolar disorder , substance disorder , recent mental health specialty care , or suicidality were excluded . INTERVENTION A telephonic outreach and care management program encouraged workers to enter outpatient treatment ( psychotherapy and /or antidepressant medication ) , monitored treatment quality continuity , and attempted to improve treatment by giving recommendations to providers . Participants reluctant to enter treatment were offered a structured telephone cognitive behavioral psychotherapy . MAIN OUTCOME MEASURES Depression severity ( Quick Inventory of Depressive Symptomatology , QIDS ) and work performance ( World Health Organization Health and Productivity Question naire [ HPQ ] , a vali date d self-report instrument assessing job retention , time missed from work , work performance , and critical workplace incidents ) . RESULTS Combining data across 6- and 12-month assessment s , the intervention group had significantly lower QIDS self-report scores ( relative odds of recovery , 1.4 ; 95 % confidence interval , 1.1 - 2.0 ; P = .009 ) , significantly higher job retention ( relative odds , 1.7 ; 95 % confidence interval , 1.1 - 3.3 ; P = .02 ) , and significantly more hours worked among the intervention ( beta=2.0 ; P=.02 ; equivalent to an annualized effect of 2 weeks of work ) than the usual care groups that were employed . CONCLUSIONS A systematic program to identify depression and promote effective treatment significantly improves not only clinical outcomes but also workplace outcomes . The financial value of the latter to employers in terms of recovered hiring , training , and salary costs suggests that many employers would experience a positive return on investment from outreach and enhanced treatment of depressed workers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00057590 Introduction : The aim of this study was to determine whether cognitive behavioural therapy ( CBT ) would enhance employment outcomes in worker 's compensation clients who were seeking employment . Methods : Participants were r and omly assigned to a st and ard job search assistance group that met for 4 hours/week for four weeks , or to a group that received st and ard job search assistance for 4 hours/week for the first two weeks and CBT for 4 hours/week for the next two weeks . Depression , Anxiety and Stress scores were measured prior to and on completion of the intervention , and employment outcomes were assessed at four- and ten-week follow-up . Results : Affective states decreased and employment was found more rapidly after CBT than after st and ard job search assistance . Conclusion : These findings indicate that CBT has a useful role in the rehabilitation of people on worker 's compensation who are seeking employment Clinical trials have shown better efficacy of escitalopram over citalopram , and review -based economic models the cost-effectiveness of escitalopram vs. citalopram ( br and and generic ) . No head-to-head clinical trial has , however , evaluated the cost-effectiveness of both drugs so far . The aim of this study was to assess the relative cost-effectiveness of escitalopram compared with citalopram in patients with major depressive disorder . An economic evaluation was conducted alongside a double-blind r and omized clinical trial conducted by general practitioners and psychiatrists comparing fixed doses of escitalopram ( 20 mg/day ) or citalopram ( 40 mg/day ) over 8 weeks in ambulatory care patients with major depressive disorder ( baseline Montgomery – Åsberg Depression Rating Scale score ≥30 ) . Re sources use was recorded using a st and ardized form recording use of healthcare services and days of sick leave for the 2-month pre study period and for the 8-week study period . Statistically significant improvements were observed in patients treated with escitalopram . Mean per-patient costs for the escitalopram group , compared with the citalopram group , were 41 % lower ( & U20AC;96 vs. & U20AC;163 ; P<0.05 ) from a healthcare perspective . Differences were mostly related to lower hospitalization costs for escitalopram compared with citalopram recipients , assuming a parity price between escitalopram and citalopram . Bootstrapped distributions of the cost-effectiveness ratios also showed better effectiveness and lower costs for escitalopram compared with citalopram . Escitalopram is significantly more effective than citalopram , and is associated with lower healthcare costs . This prospect i ve economic analysis demonstrated that escitalopram is a cost-effective first-line treatment option for major depressive disorder OBJECTIVE The purpose of this study was to evaluate the effectiveness of an activating intervention design ed to reduce sick leave duration in patients with emotional distress or minor mental disorders . METHOD In a 1.5-year r and omized controlled trial , 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners ' usual care . The intervention focused on underst and ing causes , developing and implementing problem-solving strategies and promoting early work resumption . Outcome measures were sick leave duration , mental health and physical health ( question naires included the Hospital Anxiety and Depression Scale , the Four-Dimensional Symptom Question naire and SF-36 ) , all measured at baseline at and 3 , 6 and 18 months later . Multilevel analyses were used to evaluate differences between groups . RESULTS The groups did not differ significantly on any of the outcome measures , except that the experimental group reported higher satisfaction with treatment . CONCLUSION Although the intervention has benefits , it was not successful at its primary goal ( i.e. , to reduce sick leave duration in patients with emotional distress or minor mental disorders ) . Programs aim ed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders , or if delivered by caregivers who are closer to the work environment than are social workers , such as occupational physicians Background : The burden imposed by common mental disorders on individuals and society calls for interventions aim ed at reducing psychological distress and improving quality of life . Aim : To study whether detection of mental disorders plus feedback to individuals and caregivers reduces psychological distress and improves quality of life in long-term sickness absence ( LSA ) , defined as continuous sick-leave for more than 8 weeks . Mental disorders were detected by Present State Examination . Methods : The study population comprised 118,000 inhabitants . During 1 year , all incident individuals on LSA were identified from public registers regarding sickness transfer income . Common Mental Disorders Screening Question naire ( CMD-SQ ) ( psychological distress ) and SF-36 ( quality of life ) were sent to 2414 incident individuals on LSA , response rate 46.7 % . In a r and omised controlled trial for individuals with a certain level of psychological distress , 420 participants were allocated to an intervention group and 416 to a control group . The dropout at 12-months follow-up was 22.4 % in the intervention group and 13.9 % in the control group . Results : There were no significant effects for individuals sick-listed with a psychiatric sick-leave diagnosis . For individuals without a psychiatric sick-leave diagnosis , significant effects were seen in the subscales of CMD-SQ ( effect sizes : 0.20—0.28 ) and in more subscales of SF-36 ( effect sizes : 0.12 - 0.22 ) . The effects varied according to socio-demographic characteristics and somatic sick-leave diagnoses . Conclusion : The intervention was most effective for individuals without a psychiatric sick-leave diagnosis sick-listed from full-time work . Thus , despite small effect sizes , the intervention may be efficient for large subgroups on LSA Background : The burden caused by psychiatric disorders on the individual and society has result ed in more studies examining interventions aim ed at reducing sickness absence . Aims : To examine if detection of undetected psychiatric disorders in long-term sickness absence ( LSA ) would improve the rate of return to work . Methods : Over one year all 2,414 incident persons on LSA in a well-defined population were within one week after eight weeks of continuous sickness absence posted the Common Mental Disorders Screening Question naire ( CMD-SQ ) to screen for mental disorders . In a r and omized controlled trial ( RCT ) , of 1,121 responding participants , persons with a minimum level of psychiatric symptoms 420 were allocated to the intervention group and 416 to the control group . The intervention was a psychiatric examination including diagnostics with Present State Examination and feedback regarding treatment and rehabilitation to the participants themselves , general practitioners and the social service taking care of the participants ’ rehabilitation back to work . Of the 420 in the intervention group 329 ( 78.3 % ) participated in the intervention . The outcomes measure was in an intention treat analysis the rate of return to work . Results : The rate of return to work was non-significantly lower for the intervention group than for the control group , except for persons without a psychiatric sick-leave diagnosis who were sick-listed from full time work , who showed a significantly higher rate of return to work in the intervention group . Conclusions : The effect of interventions for return to work depends on socio-demographic characteristics . Further studies are needed regarding interventions to improve return to work This study is a long-term follow-up of a previously published study that used the internet in the rehabilitation of people on long-term sick leave owing to chronic pain and /or burnout . The follow-up was to assess the effects over time of this kind of rehabilitation . The goals of the first study were to improve the participants ' health and work capacity . Sixty people were r and omly assigned to either a treatment or a waiting-list group . A 20-week rehabilitation programme based on 19 films on different themes was supplemented with written material and a dialogue over the internet . Fifty participants , 25 in each group , were followed up for 1 year after programme completion . They were administered the same question naire ( SF-36 , HAD , Stress Barometer ) that they had taken immediately before ( pre ) and after ( post ) the rehabilitation programme . No significant differences were found regarding stress and health between the treatment and waiting-list groups at the time of the 12-month follow-up . Significant group differences were , however , seen in work capacity ( number of hours worked per week ) : 52 % of the participants in the treatment group reported an increased work capacity , compared with only 13 % in the waiting-list group ( P=0.005 ) . Rehabilitation of people on long-term sick leave , which is carried out over the internet seems to complement other rehabilitation programmes as well BACKGROUND Major depression has far-reaching consequences for work functioning and absenteeism . In most cases depression is treated by medication and clinical management . The addition of occupational therapy ( OT ) might improve outcome . We determined the cost-effectiveness of the addition of OT to treatment as usual ( TAU ) . METHOD Sixty-two adults with major depression and a mean absenteeism of 242 days were r and omized to TAU ( out-patient psychiatric treatment ) or TAU+OT [ 6 months , including ( i ) diagnostic phase with occupational history and work reintegration plan , and ( ii ) therapeutic phase with individual sessions and group sessions ] . Main outcome domains were depression , work resumption , work stress and costs . Assessment s were at baseline and at 3 , 6 , 12 and 42 months . RESULTS The addition of OT to TAU : ( i ) did not improve depression outcome , ( ii ) result ed in a reduction in work-loss days during the first 18 months , ( iii ) did not increase work stress , and ( iv ) had a 75.5 % probability of being more cost-effective than TAU alone . CONCLUSION Addition of OT to good clinical practice does not improve depression outcome , improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness Objective The purpose of this study was to determine if a novel workplace stress management program , delivered either face-to-face or by self-help , would reduce illness and health services utilization among participants . Methods Five hundred one volunteers were r and omly allocated to one of three groups : full intervention , which received assessment and personalized self- study feedback and was offered six face-to-face , small-group sessions ; partial intervention , a self-help group that received assessment and personalized feedback by mail ; and a wait-list control group . All participants completed question naires for stress , anxiety , and coping at the start of the study and 6 and 12 months later . Health reports were completed at 0 , 3 , 6 , 9 , and 12 months . A sub sample of subjects who subscribed to a single health maintenance organization provided objective ly recorded doctor visit data across the study year . Results All three groups reported significant improvement in their stress , anxiety , and coping across the year . Full intervention participants showed a more rapid reduction in negative responses to stress than did participants from the other groups . Full-intervention subjects also reported fewer days of illness than subjects in the other groups . Objective ly measured physician visits showed a large ( 34 % ) reduction in healthcare utilization for full intervention subjects in the HMO sub sample . Conclusions These results indicated that a work-site program that focuses on stress , anxiety , and coping measurement along with small-group educational intervention can significantly reduce illness and healthcare utilization BACKGROUND Insufficient evidence exists about the effect of different therapies on work ability for patients with psychiatric disorders . The present study compares improvements in work ability in two short-term therapies and one long-term therapy . METHODS In the Helsinki Psychotherapy Study , 326 out patients with depressive or anxiety disorder were r and omly assigned to long-term and short-term psychodynamic psychotherapy , and solution-focused therapy . The patients were followed for 3 years from the start of treatment . Primary outcome measures were the Work Ability Index ( WAI ) , the Work-subscale ( SAS-Work ) of the Social Adjustment Scale ( SAS-SR ) , Perceived Psychological Functioning Scale , the prevalence of patients employed or study ing , and the number of sick-leave days . RESULTS Work ability was statistically significantly improved according to WAI ( 15 % ) , SAS-Work ( 17 % ) , and Perceived Psychological Functioning Scale ( 21 % ) during the 3-year follow-up . No differences in the work ability scores were found between two short-term therapies . The short-term therapies showed 4 - 11 % more improved work ability scores than long-term therapy at the 7 month follow-up point . During the second year of follow-up , no significant differences were found between therapies . After 3 years of follow-up , long-term therapy was more effective than the short-term therapies with 5 - 12 % more improved scores . No differences in the prevalence of individuals employed or study ing or in the number of sick-leave days were found between therapies during follow-up . CONCLUSIONS Short-term therapies give benefits more quickly than long-term therapy on work ability but in the long run long-term therapy is more effective than short-term therapies . More research is needed to confirm these findings BACKGROUND A significant percentage of patients with major depressive disorder ( MDD ) suffer from concurrent general medical conditions ( GMCs ) . OBJECTIVE The objective of this preliminary report was to describe the rates of co-occurring significant GMCs and the clinical correlates and symptom features associated with the presence of GMCs . DESIGN Baseline cross-sectional case-control study of patients enrolling in a prospect i ve r and omized multistage treatment study of MDD . SETTING Fourteen regional U.S. centers representing 19 primary care and 22 psychiatric practice s. PATIENTS One thous and five hundred out patients with DSM-IV nonpsychotic MDD . MEASUREMENTS Sociodemographic status , medical illness ratings , psychiatric status , quality of life and DSM-IV depression symptom ratings . RESULTS The prevalence of significant medical comorbidity in this population was 52.8 % ( 95 % CI 50.3 - 55.3 % ) . Concurrent significant medical comorbidity was associated with older age , lower income , unemployment , limited education , longer duration of index depressive episode and absence of self-reported family history of depression . Somatic symptoms common in MDD were endorsed at a higher rate in those with GMCs . Those without a GMC had higher rates of endorsement of impaired mood reactivity , distinct mood quality and interpersonal sensitivity . CONCLUSIONS Concurrent GMCs are common among out patients with MDD in both primary care and specialty setting s. Concurrent GMCs appear to influence the severity and symptom patterns in MDD and describe a vulnerable population with sociodemographic challenges to effective assessment and treatment Aims : To compare an innovative activating intervention with “ care as usual ” ( control group ) for the guidance of employees on sickness leave because of an adjustment disorder . It was hypothesised that the intervention would be more effective than care as usual in lowering the intensity of symptoms , increasing psychological re sources , and decreasing sickness leave duration . Methods : A prospect i ve , cluster r and omised controlled trial was carried out with 192 patients on first sickness leave for an adjustment disorder . Symptom intensity , sickness duration , and return to work rates were measured at 3 months and 12 months . Analyses were performed on an intention to treat basis . Results : At 3 months , significantly more patients in the intervention group had returned to work compared with the control group . At 12 months all patients had returned to work , but sickness leave was shorter in the intervention group than in the control group . The recurrence rate was lower in the intervention group . There were no differences between the two study groups with regard to the decrease of symptoms . At baseline , symptom intensity was higher in the patients than in a normal reference population , but decreased over time in a similar manner in both groups to approximately normal levels . Conclusion : The experimental intervention for adjustment disorders was successful in shortening sick leave duration , mainly by decreasing long term absenteeism OBJECTIVE To examine the feasibility of telephone-delivered cognitive behavioral therapy ( T-CBT ) in an occupational context , with reference to participant recruitment , treatment adherence , follow-up and effect . METHOD Eligible participants comprised all employees of a large communications company with authorized work absence due to mild/moderate mental health difficulties over a 10-month period . Fifty-three consenting participants were central ly r and omized to 12 weeks T-CBT or usual care , with minimization on age , gender and illness severity . Primary ( symptom severity ) and secondary outcomes ( self-rated work performance and productivity ) were measured at baseline and 3-months via postal question naires . Intention-to-treat analysis comprised multiple regression modeling with adjustment for missing response predictors , minimization variables and baseline values . RESULTS Twenty-three employees attended one or more T-CBT sessions . T-CBT was associated with medium-large effects sizes on clinical outcomes ( 0.63 - 0.77 ) and work productivity scores ( 0.75 - 0.88 ) . Twenty-one patients failed to return 3-month primary outcome data . Non-respondents were more likely to be male and more severely ill . CONCLUSION Delivery of T-CBT in an occupational context is feasible with evidence of potential effect . Larger-scale trials are warranted . These studies dem and assertive outreach or telephone-based assessment strategies in order to maximize participant recruitment and follow-up Objective : To evaluate the cost-effectiveness of an activating guideline -based care ( GBC ) by occupational physicians ( OPs ) . Methods : An economic evaluation was conducted in a r and omized controlled trial with police workers on sick leave due to mental health problems ( n = 240 ) . In the intervention group trained OPs provided GBC , compared with usual care with easy access to a psychologist . Sick leave data and health care costs were gathered after 1-year follow-up . Analyses comprised bootstrap techniques , cost-effectiveness planes , and acceptability curves . Results : Health care utilization costs ( & U20AC;574.532 in total ) were significantly lower in the intervention group ( mean difference −&U20AC;520 ; 95 % CI −&U20AC;980 to & U20AC;59 ) , whereas there were no significant differences in days of sick leave and productivity loss costs . Conclusions : GBC could be cost-effective , as lower direct costs lead to equal treatment outcomes of workers with common mental disorders Objective : To evaluate the effectiveness of guideline -based care ( GBC ) of workers with mental health problems , which promotes counseling by the occupational physician ( OP ) facilitating return to work ( RTW ) . Methods : In a r and omized controlled trial with police workers on sick leave due to mental health problems ( n = 240 ) , trained OPs delivered GBC in the intervention group . Time to RTW and recurrences during 1-year follow-up , analyzed using Cox proportional hazards models , were compared with usual care ( UC ) with easy access to a psychologist . Results : GBC by OPs did not result in earlier RTW than UC . Subgroup analysis showed a small effect in favor of GBC for workers with administrative functions and /or “ minor ” stress-related symptoms . Conclusions : GBC did not differ in RTW compared with UC , but may be beneficial for the majority of workers with minor stress-related disorders Objectives To evaluate the effectiveness of a participatory workplace intervention compared with usual care for sick-listed employees with distress , with regard to return to work ( RTW ) within the 12-month follow-up . Methods Employees with distress and sick-listed for 2–8 weeks were r and omised to a workplace intervention ( n=73 ) or to usual care ( n=72 ) . The participatory workplace intervention is a stepwise process involving the sick-listed employee and their supervisor , aim ed at reducing obstacles for RTW by reaching consensus about an action plan for RTW . Outcome variables were lasting RTW , cumulative sickness absence and stress-related symptoms . Results Overall , an HR of 0.99 ( 95 % CI 0.70 to 1.39 ) indicated no effect of the workplace intervention on lasting RTW . However , the workplace intervention significantly reduced the time until lasting RTW for employees who at baseline intended to return to work despite symptoms with an HR of 2.05 ( 95 % CI 1.22 to 3.45 ) . Employees who intended to return to work despite symptoms returned to work after 55 days in the workplace intervention group and 120 days in the usual care group . No such effect of the intervention was found for employees without baseline intentions to return to work despite symptoms ( HR=0.78 , 95 % CI 0.47 to 1.28 ) . Conclusions No overall effect of the participatory workplace intervention on lasting RTW was found . The workplace intervention appeared effective on lasting RTW for employees who at baseline intended to return to work despite symptoms . For employees who showed no baseline intention to return to work , the intervention did not have any effect . Other approaches are needed for this subgroup . This trial has been registered at the Dutch National Trial Register IS RCT N92307123 OBJECTIVE To evaluate the effects of a cognitive behavioural training programme and a physical activity programme for patients with stress-related illnesses . DESIGN In a r and omized controlled study , patients were allocated r and omly to 1 of 3 groups , where group 1 participated in a cognitive behavioural training programme , group 2 participated in a physical activity programme , and group 3 , the control group , was offered usual care for the course of the study . SUBJECTS A total of 75 patients participated in the study . They had been on sick leave for at least 50 % of the time for between 1 month and 2 years due to stress-related illnesses . METHODS Measurements of autonomic activity , pressure-pain thresholds and subjective ratings of health and behaviour were made before and after a 10-week intervention period , and at 6 and 12 months after the intervention . RESULTS Minor differences in autonomic activity and pressure-pain thresholds were found between the groups immediately after the intervention . At the 6- and 12-month follow-up assessment s , the differences were no longer present . Patients in the cognitive behavioural training group improved their ratings of general health compared with the physical activity group throughout the study . CONCLUSION The study showed little difference in the effect of cognitive behavioural training and physical activity , compared with usual care , for patients with stress-related illnesses This three-wave 35-year prospect i ve study used the Job Dem and s-Re sources model and life course epidemiology to examine how life conditions in adolescence ( 1961 - 1963 ) through achieved educational level and working conditions in early adulthood ( 1985 ) may be indirectly related to job burnout 35 years later ( 1998 ) . We used data ( N = 511 ) from the Finnish Healthy Child study ( 1961 - 1963 ) to investigate the hypothesized relationships by employing structural equation modeling analyses . The results supported the hypothesized model in which both socioeconomic status and cognitive ability in adolescence ( 1961 - 1963 ) were positively associated with educational level ( measured in 1985 ) , which in turn was related to working conditions in early adulthood ( 1985 ) . Furthermore , working conditions ( 1985 ) were associated with job burnout ( 1998 ) 13 years later . Moreover , adult education ( 1985 ) and skill variety ( 1985 ) mediated the associations between original socioeconomic status and cognitive ability , and burnout over a 35-year time period . The results suggest that socioeconomic , individual , and work-related re sources may accumulate over the life course and may protect employees from job burnout Background : Employment status is an important determinant of health inequalities . Among unemployed people , poor health decreases the likelihood of re-employment . Methods : A r and omised controlled trial with 6 months ’ follow-up among unemployed people with health complaints receiving social security benefits from the city of Rotterdam , The Netherl and s. In total , 456 people were assigned to the control group and 465 people to the intervention group . The intervention consisted of three sessions weekly over 12 weeks . One session a week was focused on education to enhance the ability to cope with ( health ) problems , and two weekly sessions consisted of physical activities . The primary outcome measures were perceived health , measured by the Short Form 36 Health Survey , and psychological measures mastery , self-esteem and pain-related fear of movement . Secondary outcome measures were work values , job search activities and re-employment . Results : Enrolment in the intervention programme was 65 % , and 72 % completed the programme with over 70 % attendance at all sessions . The intervention had a good reach among subjects with lower education , but had no effect on mental and physical health , mastery , self-esteem and pain-related fear of movement . Participation in the programme had no influence on work values , job search activities or re-employment . Conclusion : This intervention programme aim ed at the promotion of physical and mental health in unemployed people with health complaints did not show beneficial effects . The lack of integration into regular vocational rehabilitation activities may have interfered with these findings . This particular health programme can not be recommended for implementation BACKGROUND Emotional distress has major implication s for employees and employers . Cognitive behavioural therapy ( CBT ) is a recommended treatment , but dem and outstrips supply . CBT is well suited to computerization . Most employee assistance programmes have not been systematic ally evaluated and computerized CBT has not previously been studied in the workplace . AIMS To evaluate the effect of an 8 week computerized cognitive behavioural therapy programme , ' Beating The Blues ' , on emotional distress in employees with recent stress-related absenteeism , and to explore the reasons for non-participation . METHODS An open , r and omized trial in a London NHS occupational health department . Forty-eight public sector employees , with 10 or more cumulative days stress-related absenteeism in the last 6 months , r and omized equally to ' Beating The Blues ' plus conventional care , or conventional care alone . Main outcome measures were Hospital Anxiety and Depression Scale and Attributional Style Question naire scores at end of treatment and 1 , 3 and 6 months later ; and reasons for non-participation . RESULTS At end of treatment and 1 month later , adjusted mean depression scores and adjusted mean negative attributional style scores were significantly lower in the intervention group . One month post-treatment , adjusted mean anxiety scores were also significantly lower in the intervention group . The differences were not statistically significant at 3 and 6 months post-treatment . Non-participation was common and related to access problems , preference for other treatments , time commitment , scepticism about the intervention and the employer connection . CONCLUSIONS ' Beating The Blues ' may accelerate psychological recovery in employees with recent stress-related absenteeism . Greater flexibility and accessibility might improve uptake Abstract Aim : To assess the relative cost effectiveness of escitalopram compared with venlafaxine XR in patients with major depressive disorder ( MDD ) . Methods : An economic evaluation was conducted alongside a double-blind , multinational , r and omised clinical trial and examined the costs and quality of life of 251 patients taking escitalopram versus venlafaxine . Out patients fulfilling criteria for MDD were r and omised to receive oral escitalopram 10–20 mg/day or venlafaxine 75–150 mg/day for 8 weeks . Patient-reported outcomes ( EuroQOL question naire , Quality of Life Depression Scale ) , use of medical services and absence from work ( relating to the previous 3 months ) were recorded at baseline , with repeated measurements at week 8 . Unit costs in year values were applied to the re source utilisation data . A cost-effectiveness analysis was performed using the EuroQOL score as the effectiveness measure . The perspective was that of the healthcare payer , with a societal perspective considered in a sensitivity analysis . Results : Statistically significant improvements in patient-reported outcomes ( vs baseline ) were observed in both groups after 8 weeks ’ treatment . Patients treated with escitalopram tended to report fewer problems on the EuroQOL dimensions than venlafaxine recipients . Mean per-patient costs in euros ( € , year 2003 values ) for the escitalopram group , compared with the venlafaxine group , were 32 % lower ( € 110 vs € 161 ) from a healthcare perspective , although this was not a statistically significant difference . Differences were related to lower drug acquisition costs and fewer hospitalisations for escitalopram than venlafaxine recipients . A multivariate model adjusting for baseline characteristics showed that escitalopram reduced direct costs compared with venlafaxine ( p = 0.007 ) . Bootstrapped distributions of the incremental cost-effectiveness ratios also showed similar effectiveness but lower costs for escitalopram compared with venlafaxine . Inclusion of indirect costs led to similar results . Conclusion : This prospect i ve economic analysis suggests that escitalopram has similar effectiveness to venlafaxine in the treatment of MDD , but may be associated with lower healthcare costs . These findings are consistent with previously published economic evaluations A natural one-year work-life intervention to improve occupational health and reduce absenteeism was design ed as a field experiment . The intervention allowed the employees in the health care sector of a municipality to take up to five days of self-administered sick leave with full financial compensation up to four times a year . 165 employees in the intervention group and 100 employees in the control group filled out a question naire before and after the intervention . The result showed no evidence of misuse of this sick-leave option and some positive subjective health effects were found among those who used the option . Slight improvements were found in musculoskeletal problems and for cold/influenza . There were no effects on overall absenteeism . The question of the impact of local cultures on interventions to improve occupational health is also discussed Background : The lack of efficient medical interventions for combating increasing sickness absence rates has lead to the introduction of alternative measures initiated by the Norwegian National Insurance Service or at workplaces . Aim : To determine whether minimal postal intervention had any effect on the length of sick leave . Methods : R and omised , controlled trial with a one year follow up in Northern Norway in 1997 and 1998 ; 990 consecutive newly sick-listed persons with musculoskeletal or mental disorders were studied . Within the intervention group , 495 eligible sick-listed persons received a general information letter and a question naire as their sick leave passed 14 days . Possible intervention effects were analysed by survival analysis of the probability of returning to work within one year , and logistic regressions with benefits at one year as the dependent variable . Results : The overall reduction of 8.3 ( 95 % CI −22.5 to 6.0 ) calendar days in mean length of sick leaves in the intervention group compared to controls , was not statistically significant . However , intervention significantly reduced length of sick leaves in subgroups with mental disorders , and with rheumatic disorders and arthritis , and overall for sick leaves lasting 12 weeks or more . Young people with low back pain showed an adverse effect to intervention . The overall relative risk of receiving benefits due to sickness after one year in the intervention group was 0.69 ( 95 % CI 0.51 to 0.93 ) compared to controls . Conclusion : The results should encourage employers , insurance institutions , and authorities to initiate challenges as questions on the length of sick leave and possible modified work measures , during the first few weeks of sick leave , for at least some groups of sick-listed persons The authors report the results of their controlled study to compare the efficacy of day versus inpatient hospitalization for those patients for whom both treatments are equally feasible clinical ly . Newly admitted in patients from the catchment area were r and omly assigned to either day or inpatient care . Outcome evaluations , including measures of psychopathology and role function , were conducted at various follow-up intervals . The authors found clear evidence of the superiority of day treatment on virtually eveny measure used to evaluate outcome OBJECTIVE To evaluate a vocational multidisciplinary rehabilitation programme for patients on long-term sick leave with respect to their work ability and return to work . METHODS A multidisciplinary rehabilitation programme was administered to an intervention group of 183 patients on long-term sick leave ( mean 12.2 months ) . Effects of the treatment were compared with a control group ( n = 96 ) recruited from the national sickness insurance record of patients on sick leave of 6 - 12 months duration ( mean 11.5 months ) . Perceived work ability , return to work , background factors and psychosocial aspects of work were assessed on the basis of question naires at baseline and after 4 months . RESULTS Perceived work ability of the intervention group improved significantly after 4 months compared with the control group ( p < 0.01 ) . In the intervention group , 80 % had returned to work compared with 66 % in the control group ( p = 0.06 ) . Return to work after 4 months was predicted by good work ability at baseline , improved work motivation , improved work ability at follow-up and increased rumours of change in the workplace ( R2 26.1 - 38.6 % , p < 0.05 ) . CONCLUSION This multidisciplinary rehabilitation programme significantly improved perceived work ability compared with treatment as usual Objectives The aim of the study was to evaluate the effectiveness of two brief preventive stress reduction programs — a cognitive focused program and a combined intervention of physical exercise and relaxation — on sickness absence in stressed and non-stressed employees working in various jobs in a telecom company . Methods The study was design ed as an a priori r and omized trial and the follow-up period for sickness absence was 1 year . Sickness absence data of 242 employees were analyzed with respect to spells of sickness ( frequency , incidence rate ) , days ( length , duration ) and time between intervention and first subsequent absent spell . Results For stressed employees this study suggests that the illness burden represented by absenteeism is not affected by the interventions . There is no substantial difference in effectiveness between the cognitive and physical interventions . However , in comparison with the physical intervention the cognitive intervention decreases the period between the intervention and the first recurrence of a sick leave period with 144 days ( marginal significant ) . Conclusion The illness burden represented by absenteeism is effected in detail but not substantially by the interventions This study investigates utilization of the Internet in the rehabilitation of people on long-term sick leave with chronic pain and /or burnout . Fifty-five people were r and omly assigned to two groups : a treatment group ( n=27 ) that participated in a rehabilitation course over the Internet and a waiting list group ( n=28 ) . The goals were to improve participants ' health and increase quality of life , and , for those who were not on permanent disability pensions , to increase work capacity , if possible . A 20-week program , based on 19 films on different themes , was supplemented with written material and a Socratic dialogue over the Internet . Upon completion of the rehabilitation course , statistically significant improvements were observed in the treatment group in comparison to the waiting list group , for variables such as depression , pain , vitality , social function , performance problems involving work or other activities due to physical illness and the presence of stress symptoms . Thirteen of 23 individuals ( 57 % ) also increased their work capacity . The number needed to treat regarding recovering from anxiety and depression was 2 . For increased work capacity , the number needed to treat was 3 . Rehabilitation of people on long-term sick leave carried out over the Internet is a good complement to other rehabilitation programs . Die vorliegende Studie befasst sich mit der Nutzung des Internets bei der Rehabilitation von Langzeitkranken mit chronischen Schmerzen und/oder Burnout-Syndrom . Zwei Gruppen wurden insgesamt 55 Studienteilnehmer r and omisiert zugeordnet , d. h. einer Therapiegruppe ( n=27 ) , die an einem Internet-basierten Reha-Kurs teilnahm , und einer Wartelistengruppe ( n=28 ) . Die Ziele waren die gesundheitliche Verbesserung der Teilnehmer und die Steigerung der Lebensqualität und – für diejenigen , die nicht permanent eine Erwerbsunfähigkeitsrente bezogen – nach Möglichkeit eine Steigerung der Arbeitsleistung . Ein 20-Wochen-Programm auf der Grundlage von 19 Filmen zu unterschiedlichen Themen wurde durch schriftliches Material und einen sokratischen Dialog per Internet ergänzt . Nach Beendigung des Reha-Kurses wurden in der Therapiegruppe verglichen mit der Wartelistengruppe statistisch signifikante Verbesserungen bei Variablen wie Depression , Schmerzen , Lebenskraft , gesellschaftliche Funktion , Leistungsprobleme bei der Arbeit oder and eren Aktivitäten infolge von körperlicher Krankheit und das Vorh and ensein von Stresssymptomen beobachtet . Dreizehn von 23 Teilnehmern ( 57 % ) steigerten zudem ihre Arbeitsleistung . Wegen der Rekonvaleszenz von Angstgefühlen und Depression mussten insgesamt zwei Teilnehmer beh and elt werden , bei der Steigerung der Arbeitsleistung lag die Zahl bei drei . Mit einer Internet-basierten Rehabilitation von Langzeitkranken lassen sich and ere Reha-Programme gut ergänzen . Este estudio investiga la utilización de Internet en la rehabilitación de individuos con ausencia prolongada al trabajo por enfermedad , por padecer dolor crónico o el síndrome del desgaste profesional , o ambos . Se distribuyeron a 55 individuos al azar en dos grupos : un grupo de tratamiento ( n=27 ) , quienes participaron en un curso de rehabilitación impartido mediante Internet , y un grupo en lista de espera ( n=28 ) . Los objetivos fueron mejorar la salud y calidad de vida de los participantes y , para aquellos que no estaban percibiendo pensión de invalidez permanente , aumentar la capacidad de trabajo , de ser posible . Se aplicó un programa de 20 semanas , por Internet , en el que se emplearon 19 películas sobre diferentes temas , complementadas con material es escritos y un diálogo socrático . Al terminar el curso de rehabilitación se hallaron mejorías estadísticamente significativas en el grupo sometido a tratamiento , a diferencia del grupo en la lista de espera , en relación con variables tales como la depresión , el dolor , la vitalidad , la función social , problemas de rendimiento en el trabajo o al realizar otras actividades debido a la presencia de enfermedades orgánicas , y la presencia de síntomas de estrés . Trece de los 23 individuos ( 57 % ) mejoraron su capacidad de trabajo . De estas personas , 2 recibieron el tratamiento como alivio a la ansiedad y depresión que padecían ; y 3 para mejorar su capacidad de trabajo . La rehabilitación de individuos con ausencia prolongada al trabajo por enfermedad , mediante Internet , es un buen complemento al resto de los programas de rehabilitación empleados . Cette étude s'intéresse à l'utilisation de l'Internet pour la rééducation des individus en congé maladie de longue durée souffrant de douleurs chroniques et/ou d'épuisement . Cinquante-cinq personnes ont été réparties de manière aléatoire dans deux groupes ; un groupe de traitement ( n=27 ) , qui a participé au stage de rééducation sur Internet , et un groupe sur liste d'attente ( n=28 ) . Les objectifs étaient d'améliorer la santé et la qualité de vie des participants et , pour les individus ne bénéficiant pas de pensions d'invalidité permanentes , d'accroître la capacité de travail dans la mesure du possible . Un programme sur 20 semaines , reposant sur 19 films consacrés à des thèmes différents , a été complété par des matériaux écrits et un dialogue socratique via l'Internet . À la fin du stage de rééducation , des améliorations statistiquement significatives ont été observées chez le groupe de traitement par rapport au groupe sur liste d'attente , notamment pour les variables comme la dépression , la douleur , la vitalité , la fonction sociale , les problèmes de performances dus à la maladie physique et impliquant le travail ou d'autres activités , et la présence de symptômes de stress . Treize des 23 participants ( 57 % ) ont également augmenté leur capacité de travail . Le nombre d'individus à traiter pour des problèmes d'anxiété et de dépression était de 2 . Pour l'augmentation de la capacité de travail , le nombre à traiter était de 3 . La rééducation des individus en congé maladie de longue durée via l'Internet constitue un bon complément aux autres programmes de rééducation Background Despite an increase in the occurrence of burnout , there is no agreement on what kind of rehabilitation these patients should be offered . Purpose Primary aim of this study was to evaluate effects on psychological variables and sick leave rates by two different group rehabilitation programs for patients on long-term sick leave because of burnout . Rehabilitation program A ( Cognitively oriented Behavioral Rehabilitation ( CBR ) and Qigong ) was compared with rehabilitation program B ( Qigong only ) . Method In a r and omized clinical trial , 96 women and 40 men with a mean age of 41.6 ± 7.4 years were allocated to one of the two rehabilitation programs . Results A per- protocol analysis showed no significant difference in treatment efficacy between the groups . Both groups improved significantly over time with reduced levels of burnout , self-rated stress behavior , fatigue , depression , anxiety , obsessive – compulsive symptoms , and sick leave rates . In an intention-to-treat analysis , patients in program A had fewer obsessive – compulsive symptoms and larger effect sizes in self-rated stress behavior and obsessive – compulsive symptoms compared to patients in program B. Conclusion This study showed no differences in effect between CBR and Qigong compared with Qigong only in a per- protocol analysis . Both rehabilitation programs showed positive effect for patients with burnout Although group therapy is widely used for individuals with substance use disorders ( SUDs ) , r and omized clinical trials ( RCTs ) comparing the same treatment in a group versus individual format are rare . This paper presents the results of a RCT comparing guided self-change ( GSC ) treatment , a cognitive-behavioral motivational intervention , conducted in a group versus individual format with 212 alcohol abusers and 52 drug abusers who voluntarily sought outpatient treatment . Treatment outcomes demonstrated significant and large reductions in clients ' alcohol and drug use during treatment and at the 12-month follow-up , with no significant differences between the group and individual therapy conditions . A therapist time ratio analysis found that it took 41.4 % less therapist time to treat clients using the group versus the individual format . Participants ' end-of-treatment group cohesion scores characterized the groups as having high engagement , low levels of interpersonal conflict , and low avoidance of group work , all desirable group characteristics . These findings suggest that the GSC treatment model was effectively integrated into a brief group treatment format . Health care cost containment compels further evaluations of the efficacy of group treatments for SUDs |
2,378 | 30,320,145 | The model is also shown to be scientifically parsimonious using st and ard measures . | Fuzzy-trace theory assumes that decision-makers process qualitative “ gist ” representations and quantitative “ verbatim ” representations in parallel .
We develop a lattice model of fuzzy-trace theory that explains both processes .
Specifically , the model provides a novel formalization of how ( a ) decision-makers encode multiple representations of options in parallel , ( b ) representations compete or combine so that choices often turn on the simplest representation of encoded gists , and ( c ) choices between representations are made based on positive versus negative valences associated with social and moral principles stored in long-term memory ( e.g. , saving lives is good ) .
The model integrates effects of individual differences in numeracy , metacognitive monitoring and editing , and sensation seeking . | Psychological theories of categorization generally focus on either rule- or exemplar-based explanations . We present 2 experiments that show evidence of both rule induction and exemplar encoding as well as a connectionist model , ATRIUM , that specifies a mechanism for combining rule- and exemplar-based representation . In 2 experiments participants learned to classify items , most of which followed a simple rule , although there were a few frequently occurring exceptions . Experiment 1 examined how people extrapolate beyond the range of training . Experiment 2 examined the effect of instance frequency on generalization . Categorization behavior was well described by the model , in which exemplar representation is used for both rule and exception processing . A key element in correctly modeling these results was capturing the interaction between the rule- and exemplar-based representations by using shifts of attention between rules and exemplars Counseling women about breast cancer risks has been found to decrease screening compliance . We investigated whether women 's reactions to risk information are an artifact of requiring women to estimate the risk of breast cancer prior to receiving risk information . Three hundred and fifty-six women were r and omized to either make or not make a risk estimate prior to receiving risk information . Outcome measures were participants ' estimates of the average woman 's breast cancer risk and their emotional response to the risk information . Women overestimated the lifetime risk of breast cancer ( M = 46 % ) . Women who made risk estimates felt more relieved about the risk and perceived the risk as being lower than women who did not make estimates ( p 's < 0.001 ) . Asking people to estimate risks influenced their subsequent perceptions of the risk of breast cancer In the present study , the authors investigated the effects of framing of options on risky decision making in groups of younger adults ( M = 23.8 years , n = 192 ) and older adults ( M = 69.1 years , n = 192 ) . The participants were assigned to one of three scenarios varying in the goods at stake ( human lives , paintings , money ) . The authors observed a majority preference in favor of the risky options after negative , but not positive framing . They also found , as they had predicted , that the type of framing effect varied across scenarios , with a bidirectional framing effect for the life-death scenario and unidirectional ( risk averse ) framing effects when public property ( paintings ) or personal property ( money ) were at stake . It is important to note that these choice preference patterns were highly similar across the age groups , which reinforced the conclusion that younger and older adults are equally susceptible to framing effects |
2,379 | 30,525,112 | Funnel plots of EQIs and observational studies showed asymmetric distributions and potential for small study bias .
There is some evidence that non-cognitive skills associate with improved outcomes .
Interventions design ed to develop children ’s non-cognitive skills could potentially improve outcomes . | Success in school and the labour market relies on more than high intelligence .
Associations between ‘ non-cognitive ’ skills in childhood , such as attention , self-regulation and perseverance , and later outcomes have been widely investigated . | Background Given that relatively little is known about the development of resilience in early childhood , this longitudinal study aim ed to identify preschool re source factors associated with young children ’s mental health resilience to family adversity . Methods A community sample of 474 young Australian children was assessed in preschool ( mean age 4.59 years , 49 % male ) , and again two years later after their transition into formal schooling . At each assessment , st and ard question naires were used to obtain ratings from both parents and teachers about the quality of children ’s relationships with parents and teachers , children ’s self-concept and self-control , mental health ( Strengths and Difficulties Question naire ) , and family adversities ( including stressful life events and socioeconomic disadvantage ) . Results Greater exposure to cumulative family adversities was associated with both greater teacher- and parent-reported child mental health difficulties two years later . Multiple method ologies for operationalizing resilience were used to identify re sources associated with resilient mental health outcomes . Higher quality child – parent and child-teacher relationships , and greater child self-concept and self-control were associated with resilient mental health outcomes . With the exception of child-teacher relationships , these re sources were also prospect i ve antecedents of subsequent resilient mental health outcomes in children with no pre-existing mental health difficulties . Child – parent relationships and child self-concept generally had promotive effects , being equally beneficial for children facing both low- and high-adversity . Child self-control demonstrated a small protective effect on teacher-reported outcomes , with greater self-control conferring greater protection to children under conditions of high-adversity . Conclusions Findings suggest that early intervention and prevention strategies that focus on fostering child-adult relationship quality , self-concept , and self-control in young children may help build children ’s mental health and their resilience to family adversities OBJECTIVE : To evaluate the impact of an early childhood , family-centered , school-based intervention on children ’s kindergarten academic achievement . METHODS : This was a cluster ( school ) r and omized controlled trial with assessment s from pre-kindergarten ( pre-k ) entry through the end of kindergarten . The setting was 10 public elementary schools with 26 pre-k classes in 2 school districts in urban disadvantaged neighborhoods serving a largely black , low-income population . Participants were 1050 black and Latino , low-income children ( age 4 ; 88 % of pre-k population ) enrolled in 10 schools over 4 years . Universal intervention aim ed to promote self-regulation and early learning by strengthening positive behavior support and effective behavior management at home and school , and increasing parent involvement in education . Intervention included after-school group sessions for families of pre-k students ( 13 2-hour sessions ; co-led by pre-k teachers ) and professional development for pre-k and kindergarten teachers . The outcome measures were st and ardized test scores of kindergarten reading , writing , and math achievement by independent evaluators masked to intervention condition ( primary outcome ) ; developmental trajectories of teacher-rated academic performance from pre-k through kindergarten ( secondary outcome ) . RESULTS : Relative to children in control schools , children in intervention schools had higher kindergarten achievement test scores ( Cohen ’s d = 0.18 , mean difference = 2.64 , SE = 0.90 , P = .03 ) and higher teacher-rated academic performance ( Cohen ’s d = 0.25 , mean difference = 5.65 , SE = 2.34 , P = .01 ) . CONCLUSIONS : Early childhood population -level intervention that enhances both home and school environments shows promise to advance academic achievement among minority children from disadvantaged , urban neighborhoods Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems Self-regulatory abilities are robust predictors of important outcomes across the life span , yet they are rarely taught explicitly in school . Using a r and omized controlled design , the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum ( KC ) delivered in a public school setting on executive function , self-regulation , and prosocial behavior in a sample of 68 preschool children . The KC intervention group showed greater improvements in social competence and earned higher report card grade s in domains of learning , health , and social-emotional development , whereas the control group exhibited more selfish behavior over time . Interpretation of effect sizes overall indicate small to medium effects favoring the KC group on measures of cognitive flexibility and delay of gratification . Baseline functioning was found to moderate treatment effects with KC children initially lower in social competence and executive functioning demonstrating larger gains in social competence relative to the control group . These findings , observed over a relatively short intervention period , support the promise of this program for promoting self-regulation and prosocial behavior in young children . They also support the need for future investigation of program implementation across diverse setting Background : Childhood is important and critical period in human life . The foundation of ego is shaped in childhood . Play therapy is one of the successful strategies to help children with inner conflicts problems . This method of psychotherapy is base on the normal learning processes of children , provides solutions to relieve feelings of stress , and exp and s self-expression . Group play therapy can enhance the self-awareness , self- regulation , social communication , empathy and adoptability in children . Methods : Present study investigated the effects of play therapy on relational and emotional skills of pre-school children . For this purpose , the total numbers of 372 pre-school children were r and omly selected , and divided into two equal groups ( case and control ) . In next step , the BUSSE-SR methodology was used for evaluation and comparison of self-awareness , self-regulation , social interaction , empathy , adoptability , and control groups . Pre-test were performed for both groups and case group was involved in-group play therapy . According to the results of post-test , correlation of variables between case-control groups was examined by multivariate analysis of covariance . Results : Frequency of boys and girls in our sample were 51.3 and 48.7 percent , respectively . The mean age of children was 5.1±0.6 year . According to the results of present study , play therapy significantly enhanced the social-emotional skills ( P < 0.001 ) . Our findings are consistent with the results of previous studies in other nations with different environmental and cultural properties . In conclusion , it seems that play therapy can be used in pre-school centers to help children learn problem-solving skills and communicate with others Background Little is known about how contributing factors of development change during early childhood in Japan . The aim of this study was to investigate the factors that contributed to the developmental attainment of children between 9 and 18 months of age using prospect i ve longitudinal data from a developmental cohort study . Methods We used data from observations at 3 time points ( at infant age of 4 , 9 and 18 months ) in the Japan Children ’s Study . Mothers were administered question naires that requested information about their child ’s perinatal outcomes , temperament , family structure , family income , parental education , parenting stress , and child-rearing environment at home . At 9 and 18 months , mothers completed the Kinder Infant Development Scale to evaluate their child ’s development . Results A total of 284 children were available for analysis . Female children and children having siblings had higher probability of attaining developmental norms at 18 months than male and only children . Birth weight , gestational age , and temperament were associated with development at 9 months , but the effects of gestational age and temperament on development disappeared at 18 months . Stimulation from the mother at 9 months was not only related to development at that age but also promoted development at 18 months . Conclusions Our findings suggest that the role of family environmental factors such as early mother ’s stimulation and sibling ’s existence in development during early childhood might become more important as the child gets older Research Findings : The purpose of this study was to test the premise that children 's effortful control ( EC ) is prospect ively related to their academic achievement and to specify mechanisms through which EC is related to academic success . We used data from 214 children ( M age at Time 1 [ T1 ] = 73 months ) to test whether social functioning ( e.g. , social competence and externalizing problems ) mediated the relations between EC and academic achievement . Children 's adult-reported and observed EC were assessed at T1 . Parents ' and teachers ' reports of social functioning were obtained 2 years later ( T2 ) , whereas teachers ' and children 's reports of academic achievement were obtained 4 years after T2 ( T3 ) . Children 's T2 social functioning fully mediated the relation between T1 EC and T3 academic achievement in a structural equation model . Practice or Policy : Findings highlight the importance of considering social and emotional processes when attempting to improve academic achievement and have implication s for curriculum developers and professionals working in preschool programs and elementary schools Social experiments are powerful sources of information about the effectiveness of interventions . In practice , initial r and omization plans are almost always compromised . Multiple hypotheses are frequently tested . " Significant " effects are often reported with p-values that do not account for preliminary screening from a large c and i date pool of possible effects . This paper develops tools for analyzing data from experiments as they are actually implemented . We apply these tools to analyze the influential HighScope Perry Preschool Program . The Perry program was a social experiment that provided preschool education and home visits to disadvantaged children during their preschool years . It was evaluated by the method of r and om assignment . Both treatments and controls have been followed from age 3 through age 40 . Previous analyses of the Perry data assume that the planned r and omization protocol was implemented . In fact , as in many social experiments , the intended r and omization protocol was compromised . Accounting for compromised r and omization , multiple-hypothesis testing , and small sample sizes , we find statistically significant and economically important program effects for both males and females . We also examine the representativeness of the Perry study This study examines the role of one component of emotion regulation , behavioral control , in the growth of children 's early behavior problems by examining whether increases in parental positive behavior support brought about by a family-centered intervention were associated with greater child behavioral control , and whether greater behavioral control at age 3 mediated the association between improvements in aspects of positive behavior support from ages 2 to 3 and decreases in growth of behavior problems from ages 2 to 4 . The sample included 713 at-risk children ( 50 % female ) and their primary caregivers ( 50 % European American , 28 % African American , 13 % biracial , 9 % other ) who were r and omly assigned to the intervention or control group . Children had a mean age of 29.91 months at the initial assessment . Data were collected through home visits at child ages 2 to 4 , which involved question naires for primary caregivers and structured and unstructured play activities for children with primary and alternative caregivers and siblings . Results indicated that the intervention improved parental positive behavior support and reduced growth of child behavior problems . One dimension of positive behavior support , proactive parenting , was modestly associated with behavioral control at age 3 , which in turn was significantly associated with growth in behavior problems from ages 2 to 4 , with greater behavioral control related to lower levels of growth in behavior problems . Results provide support for the notion that proactive parenting is an important factor in the development of children 's behavioral control and that behavioral control plays an important role in the growth of behavior problems Based on theoretically driven models , the Chicago School Readiness Project ( CSRP ) targeted low-income children 's school readiness through the mediating mechanism of self-regulation . The CSRP is a multicomponent , cluster-r and omized efficacy trial implemented in 35 Head Start-funded classrooms ( N = 602 children ) . The analyses confirm that the CSRP improved low-income children 's self-regulation skills ( as indexed by attention/impulse control and executive function ) from fall to spring of the Head Start year . Analyses also suggest significant benefits of CSRP for children 's preacademic skills , as measured by vocabulary , letter-naming , and math skills . Partial support was found for improvement in children 's self-regulation as a hypothesized mediator for children 's gains in academic readiness . Implication s for programs and policies that support young children 's behavioral health and academic success are discussed Research Findings : This study examined processes of change associated with the positive preschool and kindergarten outcomes of children who received the Head Start REDI ( REsearch -based , Developmentally Informed ) intervention compared to usual practice Head Start . Using data from a large-scale r and omized controlled trial ( N = 356 children , 42 % African American or Latino , all from low-income families ) , this study tests the logic model that improving preschool social-emotional skills ( e.g. , emotion underst and ing , social problem solving , and positive social behavior ) as well as language /emergent literacy skills will promote cross-domain academic and behavioral adjustment after children transition into kindergarten . Validating this logic model , the present study finds that intervention effects on 3 important kindergarten outcomes ( e.g. , reading achievement , learning engagement , and positive social behavior ) were mediated by preschool gains in the proximal social-emotional and language /emergent literacy skills targeted by the REDI intervention . It is important to note that preschool gains in social-emotional skills made unique contributions to kindergarten outcomes in reading achievement and learning engagement , even after we accounted for concurrent preschool gains in vocabulary and emergent literacy skills . Practice or Policy : These findings highlight the importance of fostering at-risk children 's social-emotional skills during preschool as a means of promoting school readiness While numerous studies have investigated the efficacy of interventions at increasing children 's vegetable consumption , little research has examined the effect of individual characteristics on intervention outcomes . In previous research , interventions consisting of modelling and rewards have been shown to increase children 's vegetable intake , but differences were identified in terms of how much children respond to such interventions . With this in mind , the current study investigated the role of parental feeding practice s , child temperament , and child eating behaviours as predictors of intervention success . Parents ( N = 90 ) of children aged 2 - 4 years were recruited from toddler groups across Leicestershire , UK . Parents completed measures of feeding practice s , child eating behaviours and child temperament , before participating in one of four conditions of a home-based , parent led 14 day intervention aim ed at increasing their child 's consumption of a disliked vegetable . Correlations and logistic regressions were performed to investigate the role of these factors in predicting intervention success . Parental feeding practice s were not significantly associated with intervention success . However , child sociability and food fussiness significantly predicted intervention success , producing a regression model which could predict intervention success in 61 % of cases . These findings suggest that future interventions could benefit from being tailored according to child temperament . Furthermore , interventions for children high in food fussiness may be better targeted at reducing fussiness in addition to increasing vegetable consumption Effective early education is essential for academic achievement and positive life outcomes , particularly for children in poverty . Advances in neuroscience suggest that a focus on self-regulation in education can enhance children ’s engagement in learning and establish beneficial academic trajectories in the early elementary grade s. Here , we experimentally evaluate an innovative approach to the education of children in kindergarten that embeds support for self-regulation , particularly executive functions , into literacy , mathematics , and science learning activities . Results from a cluster r and omized controlled trial involving 29 schools , 79 classrooms , and 759 children indicated positive effects on executive functions , reasoning ability , the control of attention , and levels of salivary cortisol and alpha amylase . Results also demonstrated improvements in reading , vocabulary , and mathematics at the end of kindergarten that increased into the first grade . A number of effects were specific to high-poverty schools , suggesting that a focus on executive functions and associated aspects of self-regulation in early elementary education holds promise for closing the achievement gap Follow-up data , obtained 4 - 7 years after intervention ended , are presented for the Carolina Abecedarian Project , an experimental study of early childhood educational intervention for children from poverty families . Subjects were r and omly assigned to 1 of 4 intervention conditions : educational treatment from infancy through 3 years in public school ( up to age 8) ; preschool treatment only ( infancy to age 5 ) ; primary school treatment only ( age 5 - 8 years ) , or an untreated control group . Positive effects of preschool treatment on intellectual development and academic achievement were maintained through age 12 . School-age treatment alone was less effective . Results generally supported an intensity hypothesis in that scores on cognitive and academic achievement measures increased as duration of treatment increased The additive and interactive relations of parenting styles ( authoritative and authoritarian parenting ) and child temperament ( anger/frustration , sadness , and effortful control ) to children 's internalizing problems were examined in a 3.8-year longitudinal study of 425 Chinese children ( aged 6 - 9 years ) from Beijing . At Wave 1 , parents self-reported on their parenting styles , and parents and teachers rated child temperament . At Wave 2 , parents , teachers , and children rated children 's internalizing problems . Structural equation modeling indicated that the main effect of authoritative parenting and the interactions of Authoritarian Parenting × Effortful Control and Authoritative Parenting × Anger/Frustration ( parents ' reports only ) prospect ively and uniquely predicted internalizing problems . The above results did not vary by child sex and remained significant after controlling for co-occurring externalizing problems . These findings suggest that ( a ) children with low effortful control may be particularly susceptible to the adverse effect of authoritarian parenting and ( b ) the benefit of authoritative parenting may be especially important for children with high anger/frustration OBJECTIVES To determine if limited ability to delay gratification ( ATDG ) at age 4 years is independently associated with an increased risk of being overweight at age 11 years and to assess confounding or moderation by child body mass index z score at 4 years , self-reported maternal expectation of child ATDG for food , and maternal weight status . DESIGN Longitudinal prospect i ve study . SETTING Ten US sites . PARTICIPANTS Participants in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development . Main Exposure Ability to delay gratification at 4 years , measured as pass or fail on a vali date d task . OUTCOME MEASURES Overweight at 11 years , defined as a body mass index greater than or equal to the 85th percentile based on measured weight and height . RESULTS Of 805 children , 47 % failed the ATDG task . Using multiple logistic regression , children who failed the ATDG task were more likely to be overweight at 11 years ( relative risk , 1.29 ; 95 % confidence interval , 1.06 - 1.58 ) , independent of income to needs ratio . Body mass index z score at 4 years and maternal expectation of child ATDG for food did not alter the association , but maternal weight status reduced the association significantly . CONCLUSIONS Children with limited ATDG at age 4 years were more likely to be overweight at age 11 years , but the association was at least partially explained by maternal weight status . Further underst and ing of the association between the child 's ATDG and maternal and child weight status may lead to more effective obesity intervention and prevention programs Early executive control ( EC ) predicts a range of academic outcomes and shows particularly strong associations with children 's mathematics achievement . Nonetheless , a major challenge for EC research lies in distinguishing EC from related cognitive constructs that also are linked to achievement outcomes . Developmental cascade models suggest that children 's information processing speed is a driving mechanism in cognitive development that supports gains in working memory , inhibitory control and associated cognitive abilities . Accordingly , individual differences in early executive task performance and their relation to mathematics may reflect , at least in part , underlying variation in children 's processing speed . The aims of this study were to : ( 1 ) examine the degree of overlap between EC and processing speed at different preschool age points ; and ( 2 ) determine whether EC uniquely predicts children 's mathematics achievement after accounting for individual differences in processing speed . As part of a longitudinal , cohort-sequential study , 388 children ( 50 % boys ; 44 % from low income households ) completed the same battery of EC tasks at ages 3 , 3.75 , 4.5 , and 5.25 years . Several of the tasks incorporated baseline speeded naming conditions with minimal EC dem and s. Multidimensional latent models were used to isolate the variance in executive task performance that did not overlap with baseline processing speed , covarying for child language proficiency . Models for separate age points showed that , while EC did not form a coherent latent factor independent of processing speed at age 3 years , it did emerge as a distinct factor by age 5.25 . Although EC at age 3 showed no distinct relation with mathematics achievement independent of processing speed , EC at ages 3.75 , 4.5 , and 5.25 showed independent , prospect i ve links with mathematics achievement . Findings suggest that EC and processing speed are tightly intertwined in early childhood . As EC becomes progressively decoupled from processing speed with age , it begins to take on unique , discriminative importance for children 's mathematics achievement Montessori education is a 100-yearold method of schooling that was first used with impoverished preschool children in Rome . The program continues to grow in popularity . Estimates indicate that more than 5000 schools in the United States — including 300 public schools and some high schools — use the Montessori program . Montessori education is characterized by multi-age classrooms , a special set of educational material s , student-chosen work in long time blocks , collaboration , the absence of grade s and tests , and individual and small group instruction in both academic and social skills ( 1 ) . The effectiveness of some of these elements is supported by research on human learning ( 2 ) . We evaluated the social and academic impact of Montessori education . Children were studied near the end of the two most widely implemented levels of Montessori education : primary ( 3to 6-year-olds ) and elementary ( 6to 12-year-olds ) . The Montessori school we studied [ located in Milwaukee , Wisconsin ( 3 ) ] , which served mainly urban minority children , was in its ninth year of operation and was recognized by the U.S. branch of the Association Montessori Internationale ( AMI/USA ) for its good implementation of Montessori principles ( 4 ) . Because it was not feasible to r and omly assign children to experimental and control educational groups , we design ed our study around the school lottery already in place . Both the experimental and the control group had entered the Montessori school lottery ; those who were accepted were assigned to the experimental ( Montessori ) group , and those who were not accepted were assigned to the control ( other education systems ) group . This strategy addressed the concern that parents who seek to enroll their child in a Montessori school are different from parents who do not . It is crucial to control for this potential source of bias , because parents are the dominant influence on child outcomes ( 5 ) This study examined the relations of income and children 's effortful control to teacher reports of preschoolers ' social competence and adjustment problems . This study tested whether changes in effortful control accounted for the effects of income on children 's adjustment . A community sample ( N=306 ) of preschool-age children ( 36 - 40 mos . ) and their mothers , representing the full range of income ( 29 % at or near poverty , 28 % at or below the local median income ) , was used . Path analyses were used to test the prospect i ve effects of income on rank-order changes in two aspects of effortful control , executive control and delay ability , which in turn , predicted teacher-reported adjustment problems and social competence . Lower income predicted smaller rank-order change in executive control , but did not predict changes in delay ability . Smaller rank-order change in delay ability predicted greater adjustment problems above the effect of income . Larger rank-order change in executive control predicted greater social competence and fewer adjustment problems above the effect of income . These findings provided some support for the hypothesis that disruptions in the development of effortful control related to low income might account for the effects of low income on young children 's adjustment . Effortful control is potentially a fruitful target for intervention , particularly among children living in low income and poverty Minority children living in disadvantaged neighborhoods are at high risk for school dropout , delinquency , and poor health , largely due to the negative impact of poverty and stress on parenting and child development . This study evaluated a population -level , family-centered , school-based intervention design ed to promote learning , behavior , and health by strengthening parenting , classroom quality , and child self-regulation during early childhood . Ten schools in urban districts serving primarily low-income Black students were r and omly assigned to intervention or a “ pre-kindergarten education as usual ” control condition . Intervention included a family program ( a 13-week behavioral parenting intervention and concurrent group for children ) and professional development for early childhood teachers . The majority ( 88 % ) of the pre-kindergarten population ( N = 1,050 ; age 4 ) enrolled in the trial , and nearly 60 % of parents in intervention schools participated in the family program . This study evaluated intervention impact on parenting ( knowledge , positive behavior support , behavior management , involvement in early learning ) and child conduct problems over a 2-year period ( end of kindergarten ) . Intent-to-treat analyses found intervention effects on parenting knowledge , positive behavior support , and teacher-rated parent involvement . For the highest-risk families , intervention also result ed in increased parent-rated involvement in early learning and decreased harsh and inconsistent behavior management . Among boys at high risk for problems based on baseline behavioral dysregulation ( age 4 , 23 % of sample ) , intervention led to lower rates of conduct problems at age 6 . Family-centered intervention at the transition to school has potential to improve population health and break the cycle of disadvantage for low-income , minority families Background Prospect i ve studies linking infant temperament , or behavioral style , to infant body composition are lacking . In this longitudinal study ( 3 to 18 months ) , we seek to examine the associations between two dimensions of infant temperament ( distress to limitations and activity level ) and two anthropometric indicators ( weight-for-length z-scores ( WLZ ) and skin fold ( SF ) measures ) in a population at high risk of overweight . Methods Data are from the Infant Care and Risk of Obesity Project , a longitudinal study of North Carolina low income African American mother-infant dyads ( n = 206 ) . Two temperament dimensions were assessed using the Infant Behavior Question naire-Revised . A high distress to limitations score denotes an infant whose mother perceives that s/he often cries or fusses , and a high activity level score one who moves his/her limbs and squirms frequently . Cross-sectional analyses were conducted using ordinary least squares regression . Fixed effects longitudinal models were used to estimate anthropometric outcomes as a function of time varying infant temperament . Results In longitudinal models , increased activity levels were associated with later decreased fatness and WLZ . In contrast , high levels of distress to limitations were associated with later increased fatness at all time points and later increased WLZ at 12 months . Conclusion Infant temperament dimensions contribute to our underst and ing of the role of behavior in the development of the risk of overweight in the formative months of life . Identification of modifiable risk factors early in life may help target strategies for establishing healthy lifestyles prior to the onset of overweight Background We explore whether the number of null results in large National Heart Lung , and Blood Institute ( NHLBI ) funded trials has increased over time . Methods We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease . Trials were included if direct costs > $ 500,000/year , participants were adult humans , and the primary outcome was cardiovascular risk , disease or death . The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000 , whether they registered in clinical trials.gov prior to publication , used active or placebo comparator , and whether or not the trial had industry co-sponsorship . We tabulated whether the study reported a positive , negative , or null result on the primary outcome variable and for total mortality . Results 17 of 30 studies ( 57 % ) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 ( 8 % ) trials published after 2000 ( χ2=12.2,df= 1 , p=0.0005 ) . There has been no change in the proportion of trials that compared treatment to placebo versus active comparator . Industry co-sponsorship was unrelated to the probability of reporting a significant benefit . Pre- registration in clinical trials.gov was strongly associated with the trend toward null findings . Conclusions The number NHLBI trials reporting positive results declined after the year 2000 . Prospect i ve declaration of outcomes in RCTs , and the adoption of transparent reporting st and ards , as required by clinical trials.gov , may have contributed to the trend toward null findings BACKGROUND Most studies on multiple health risk behaviors among adolescents have cross-sectionally studied a limited number of health behaviors or determinants . PURPOSE To examine the prevalence , longitudinal patterns and predictors of individual and multiple health risk behaviors among adolescents . METHODS Eight health risk behaviors ( no regular consumption of fruit , vegetables or breakfast , overweight or obesity , physical inactivity , smoking , alcohol use and cannabis use ) were assessed in a prospect i ve population study ( second and third wave ) . Participants were assessed in three waves between ages 10 and 17 ( 2001 - 2008 ; n=2230 ) . Multiple linear regression was used to assess the influence of gender , self-control , parental health risk behaviors , parental monitoring and socioeconomic factors on the number of health risk behaviors adjusted for preceding multiple health risk behaviors ( analysis : 2013 - 2014 ) . RESULTS Rates of > 5 health risk behaviors were high : 3.6 % at age 13.5 and 10.2 % at age 16 . Smoking at age 13.5 was frequently associated with health risk behaviors at age 16 . No regular consumption of fruit , vegetables and breakfast , overweight or obesity , physical inactivity and smoking predicted the co-occurrence of health risk behaviors at follow-up . Significant predictors of the development of multiple health risk behaviors were adolescents ' levels of self-control , socioeconomic status and maternal smoking . CONCLUSIONS Multiple health risk behaviors are common among adolescents . Individual and social factors predict changes in multiple health risk behaviors , showing that prevention targeting multiple risk behaviors is needed . Special attention should be paid to adolescents with low self-control and families with low socioeconomic status or a mother who smokes OBJECTIVE The aim of this study is to investigate whether individual personality or temperamental qualities that emerge early and persist over the life course , predict adult midlife health . Specific childhood personality attributes considered include distress proneness , behavioral inhibition , and ability to stay focused on a task . DESIGN Prospect i ve data are from 569 individuals followed from birth into adulthood . MAIN OUTCOME MEASURES Outcomes include two different measures of adult health : self-rated general health , and number of illnesses in adulthood . RESULTS Childhood personality attributes related to attention and distress were significantly associated with adult health , with stronger effects evident among women . Children with high attention reported better self-rated health ( b = 0.12 , p < .05 ) and fewer illnesses ( b = -0.09 , p < .01 ) as adults ; more distress-prone children reported worse self-rated health ( b = -0.15 , p < .05 ) and more illnesses ( b = 0.07 , p < .09 ) as adults . CONCLUSION Associations between child personality attributes with both general self-rated health and number of illnesses in adulthood were maintained after taking account of childhood social environment and child health . Findings indicate that early emerging personality and related processes influence adult physical health , and suggest the potential value of interventions targeting early life development 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 We examined prospect i ve prediction from parent- and teacher-reported oppositional defiant disorder ( ODD ) symptoms to parent-reported ODD , conduct disorder ( CD ) , major depressive disorder ( MDD ) , and generalized anxiety disorder symptoms and whether child executive functioning abilities moderated these relations among an urban , low-income sample of first- to third- grade children ( N = 87 ) . Time 1 parent-reported ODD predicted each Time 2 outcome . Time 1 teacher-reported ODD predicted Time 2 CD and MDD symptoms . After controlling for Time 1 co-occurring symptoms , only prediction from Time 1 teacher-reported ODD to CD and MDD symptoms remained significant . Child executive functioning abilities moderated relations between Time 1 parent-reported ODD and Time 2 ODD , and Time 1 teacher-reported ODD and Time 2 CD and MDD . Among children with better executive functioning abilities , higher Time 1 ODD was associated with higher Time 2 symptoms This study examined the psychometric properties and criterion validity of a newly developed battery of executive function ( EF ) tasks for use in early childhood . The battery was included in the Family Life Project ( FLP ) , a prospect i ve longitudinal study of families who were over sample d from low-income and African American families at the birth of a new child ( N = 1,292 ) . Ninety-nine percent ( N = 1,036 ) of children who participated in the age 5 home visit completed 1 or more ( M = 5.8 , Mdn = 6 ) of the 6 EF tasks . Results indicated that tasks worked equally well for children residing in low-income and not low-income homes , that task scores were most informative about the ability level of children in the low-average range , that performance on EF tasks was best characterized by a single factor , and that individual differences on the EF battery were strongly related to a latent variable measuring overall academic achievement , as well as to individual st and ardized tests that measured phonological awareness , letter-word identification , and early math skills This prospect i ve longitudinal study focused on self-regulatory , social-cognitive , and parenting precursors of individual differences in children 's peer-directed aggression at early school age . Participants were 199 3-year-old boys and girls who were reassessed following the transition to kindergarten ( 5.5 - 6 years ) . Peer aggression was assessed in preschool and school setting s using naturalistic observations and teacher reports . Children 's self-regulation abilities and theory of mind underst and ing were assessed during a laboratory visit , and parenting risk ( corporal punishment and low warmth/responsiveness ) was assessed using interview-based and question naire measures . Individual differences in children 's peer aggression were moderately stable across the preschool to school transition . Preschool-age children who manifested high levels of aggressive peer interactions also showed lower levels of self-regulation and theory of mind underst and ing , and experienced higher levels of adverse parenting than others . Our main finding was that early corporal punishment was associated with increased levels of peer aggression across the transition from preschool to school , as was the interaction between low maternal emotional support and children 's early delays in theory of mind underst and ing . These data highlight the need for family-directed preventive efforts during the early preschool years Background Elucidating risk pathways for under‐achieving at school can inform strategies to reduce the number of adolescents leaving school without passing grade s in core subjects . Maternal depression can compromise the quality of parental care and is associated with multiple negative child outcomes . However , only a few small studies have investigated the association between perinatal maternal depression and poor academic achievement in adolescence . The pathways to explain the risks are also unclear . Method Prospect i ve observational data from 5,801 parents and adolescents taking part in a large UK population cohort ( Avon‐Longitudinal‐ Study ‐of‐Parents‐ and ‐Children ) were used to test associations between maternal and paternal depression and anxiety in the perinatal period , executive function ( EF ) at age 8 , and academic achievement at the end of compulsory school at age 16 . Results Adolescents of postnatally depressed mothers were 1.5 times ( 1.19 , 1.94 , p = .001 ) as likely as adolescents of nondepressed mothers to fail to achieve a ‘ pass ’ grade in math ; antenatal anxiety was also an independent predictor of poor math . Disruption in different components of EF explained small but significant proportions of these associations : attentional control explained 16 % ( 4 % , 27 % , p < .001 ) of the association with postnatal depression , and working memory explained 17 % ( 13 % , 30 % , p = .003 ) of the association with antenatal anxiety . A similar pattern was seen for language grade s , but associations were confounded by maternal education . There was no evidence that paternal factors were independently associated with impaired child EF or adolescent exams . Conclusion Maternal postnatal depression and antenatal anxiety are risk factors for adolescents underachieving in math . Preventing , identifying , and treating maternal mental health in the perinatal period could , therefore , potentially increase adolescents ’ academic achievement . Different aspects of EF partially mediated these associations . Further work is needed , but if these pathways are causal , improving EF could reduce underachievement in math Despite their potentially central role in fostering school readiness , executive function ( EF ) skills have received little explicit attention in the design and evaluation of school readiness interventions for socioeconomically disadvantaged children . The present study examined a set of five EF measures in the context of a r and omized-controlled trial of a research -based intervention integrated into Head Start programs ( Head Start REDI ) . Three hundred fifty-six 4-year-old children ( 17 % Hispanic , 25 % African American ; 54 % girls ) were followed over the course of the prekindergarten year . Initial EF predicted gains in cognitive and social-emotional skills and moderated the impact of the Head Start REDI intervention on some outcomes . The REDI intervention promoted gains on two EF measures , which partially mediated intervention effects on school readiness . We discuss the importance of further study of the neurobiological bases of school readiness , the implication s for intervention design , and the value of incorporating markers of neurobiological processes into school readiness interventions Data from a prospect i ve 11-year longitudinal survey were used to identify early predictors and pathways to symptoms of anxiety and depression at 12 - 13 years of age , and to examine whether there were unique predictors of anxious versus depressive symptoms . Structural equation modeling was used to explore longitudinal relations between context ual ( maternal distress , family adversities , and social support ) and temperamental ( shyness and emotionality ) risk factors in their prediction of informant-consistent symptoms of anxiety and depression . The results show that early risk factors can explain 38 % of the variance in boys ' covarying symptoms of anxiety and depression in early adolescence , and 25 % of variance in girls ' covarying symptoms . Two main pathways were identified . One pathway was through temperament , as nearly all risk factors were partly mediated through child emotionality in midchildhood . Another pathway was through early context ual risk factors , with all direct and indirect context ual impact from before 5 years of age . Family adversity uniquely predicted depressive symptoms . These findings underscore the persisting impact of context ual predictors in families with children less than 5 years of age . The importance of early interventions to prevent adolescent internalizing problems is stressed This paper reports the results from a r and omized clinical trial evaluating an adaptation of the Promoting Alternative Thinking Strategies curriculum ( PATHS ) for preschool-age children in Head Start . PATHS is a universal , teacher-taught social-emotional curriculum that is design ed to improve children ’s social competence and reduce problem behavior . Twenty classrooms in two Pennsylvania communities participated in the study . Teachers in the 10 intervention classrooms implemented weekly lessons and extension activities across a 9-month period . Child assessment s and teacher and parent reports of child behavior assessment s were collected at the beginning and end of the school year . Analysis of covariance was used to control for baseline differences between the groups and pretest scores on each of the outcome measures . The results suggest that after exposure to PATHS , intervention children had higher emotion knowledge skills and were rated by parents and teachers as more socially competent compared to peers . Further , teachers rated intervention children as less socially withdrawn at the end of the school year compared to controls . Editors ’ Strategic Implication s : n Findings from this and other r and omized clinical trials confirm that the Preschool PATHS program is clearly a promising practice for improving children ’s social and emotional competence . Head Start and school programs will find these multi-informant data to be of interest as they consider a curriculum to help prepare children for school entry Theories of temperament suggest that individual differences in affective reactivity ( e.g. , negative affectivity ) may confer risk for internalizing psychopathology in youth and that self-regulatory aspects of temperament ( e.g. , effortful control ) may protect against the deleterious effects of high negative affective reactivity . However , no study to date has examined how the relationship between temperament and youth internalizing psychopathology may be moderated by stress . The current study used a prospect i ve longitudinal design to test the interaction of temperament ( e.g. , negative affectivity and effortful control ) and stressors as a predictor of youth ( ages 7–16 ; 56 % female ; N = 576 ) depressive and anxious symptoms over a 3-month period . Findings show that at low levels of stress , high levels of effortful control protect against the development of depressive and anxious symptoms among youth with high levels of negative affectivity . However , at high levels of stress , this buffering effect is not observed . Gender and grade did not moderate this relationship . Overall , findings extend current underst and ing of how the interaction of individual psychosocial vulnerabilities and environmental factors may confer increased or decreased risk for depressive and anxious symptoms Abstract Prosocial behaviors are considered integral to intervention goals that seek to promote successful youth development . This study examines the effect of a school-based intervention program entirely design ed to promote prosocial behaviors called Promoting Prosocial and Emotional Skills to Counteract Externalizing Problems in Adolescence ( Italian acronym CEPIDEA ) . The CEPIDEA curriculum was incorporated into routine educational practice s and included five major components that reflect the personal determinants of prosocial behavior during adolescence . The present study assessed 151 students ( 48.7 % female ; Mage = 12.4 ) of the intervention school and 140 students ( 51.2 % female ; Mage = 13.0 ) of the control school at three points . A multi-group latent curve analysis revealed that the intervention group , compared with the control group , showed an increase in prosocial behavior , interpersonal self-efficacy beliefs , and agreeableness along with a decrease in physical aggression above and beyond the normative developmental trend of the these variables . Participants of the intervention also obtained higher grade s than the control group at the end of middle school . Moderation effects for prosocial behavior and agreeableness evidence d that those who benefited most from the intervention were those adolescents with lower normative development of prosocial behavior , low initial level of agreeableness , and high initial level of physical aggression . The results also showed that the increase of prosocial behaviors mediated the decline of verbal aggression in adolescents who had attended the intervention . These findings suggest that interventions aim ed at promoting prosocial behaviors while having the potential to support positive outcomes may also counteract or redirect negative trajectories of functioning The present study evaluated the efficacy of a multicomponent , classroom-based intervention in reducing preschoolers ' behavior problems . The Chicago School Readiness Project model was implemented in 35 Head Start classrooms using a clustered-r and omized controlled trial design . Results indicate significant treatment effects ( ds = 0.53 - 0.89 ) for teacher-reported and independent observations of children 's internalizing and externalizing behavior problems . Moreover , there was some evidence for the moderating role of child gender , race/ethnic group membership , and exposure to poverty-related risk , with stronger effects of intervention for some groups of children than for others . Findings contribute to a growing area of research on poverty and preventive intervention in early childhood Studies revealing transfer effects of working memory ( WM ) training on non-trained cognitive performance of children hold promising implication s for scholastic learning . However , the results of existing training studies are not consistent and provoke debates about the potential and limitations of cognitive enhancement . To examine the influence of individual differences on training outcomes is a promising approach for finding causes for such inconsistencies . In this study , we implemented WM training in an elementary school setting . The aim was to investigate near and far transfer effects on cognitive abilities and academic achievement and to examine the moderating effects of a dispositional and a regulative temperament factor , neuroticism and effortful control . Ninety-nine second- grade rs were r and omly assigned to 20 sessions of computer-based adaptive WM training , computer-based reading training , or a no-contact control group . For the WM training group , our analyses reveal near transfer on a visual WM task , far transfer on a vocabulary task as a proxy for crystallized intelligence , and increased academic achievement in reading and math by trend . Considering individual differences in temperament , we found that effortful control predicts larger training mean and gain scores and that there is a moderation effect of both temperament factors on post-training improvement : WM training condition predicted higher post-training gains compared to both control conditions only in children with high effortful control or low neuroticism . Our results suggest that a short but intensive WM training program can enhance cognitive abilities in children , but that sufficient self-regulative abilities and emotional stability are necessary for WM training to be effective Children 's behavioral self-regulation and executive function ( EF ; including attentional or cognitive flexibility , working memory , and inhibitory control ) are strong predictors of academic achievement . The present study examined the psychometric properties of a measure of behavioral self-regulation called the Head-Toes-Knees-Shoulders ( HTKS ) by assessing construct validity , including relations to EF measures , and predictive validity to academic achievement growth between prekindergarten and kindergarten . In the fall and spring of prekindergarten and kindergarten , 208 children ( 51 % enrolled in Head Start ) were assessed on the HTKS , measures of cognitive flexibility , working memory ( WM ) , and inhibitory control , and measures of emergent literacy , mathematics , and vocabulary . For construct validity , the HTKS was significantly related to cognitive flexibility , working memory , and inhibitory control in prekindergarten and kindergarten . For predictive validity in prekindergarten , a r and om effects model indicated that the HTKS significantly predicted growth in mathematics , whereas a cognitive flexibility task significantly predicted growth in mathematics and vocabulary . In kindergarten , the HTKS was the only measure to significantly predict growth in all academic outcomes . An alternative conservative analytical approach , a fixed effects analysis ( FEA ) model , also indicated that growth in both the HTKS and measures of EF significantly predicted growth in mathematics over four time points between prekindergarten and kindergarten . Results demonstrate that the HTKS involves cognitive flexibility , working memory , and inhibitory control , and is substantively implicated in early achievement , with the strongest relations found for growth in achievement during kindergarten and associations with emergent mathematics In a prospect i ve longitudinal study , we examined whether the personality trait of self-control protects against weight gain during the transition from childhood to adolescence . We obtained multi- method , multi- source measures of self-control from a socioeconomically and ethnically diverse sample of 105 fifth- grade students . Height and weight were recorded by the school nurse and used to calculate age- and gender-specific st and ardized body mass index ( BMI ) z-scores . Self-controlled fifth grade rs had lower BMI z-scores in eighth grade compared to their more impulsive peers , and this relationship remained significant when controlling for potential confounds , including gender , age , socioeconomic status , ethnicity , IQ , and happiness . Moreover , when controlling for the same covariates , self-control measured in fifth grade predicted decreases in BMI z-scores from fifth to eighth grade . These results suggest that more self-controlled children are protected from weight gain in the transition to adolescence The development of emotional regulation capacities in children at high versus low risk for externalizing disorder was examined in a longitudinal study investigating : ( a ) whether disturbances in emotion regulation precede and predict the emergence of externalizing symptoms and ( b ) whether sensitive maternal behavior is a significant influence on the development of child emotion regulation . Families experiencing high ( n = 58 ) and low ( n = 63 ) levels of psychosocial adversity were recruited to the study during pregnancy . Direct observational assessment s of child emotion regulation capacities and maternal sensitivity were completed in early infancy , at 12 and 18 months , and at 5 years . Key findings were as follows . First , high-risk children showed poorer emotion regulation capacities than their low-risk counterparts at every stage of assessment . Second , from 12 months onward , emotion regulation capacities showed a degree of stability and were associated with behavioral problems , both concurrently and prospect ively . Third , maternal sensitivity was related to child emotion regulation capacities throughout development , with poorer emotion regulation in the high-risk group being associated with lower maternal sensitivity . The results are consistent with a causal role for problems in the regulation of negative emotions in the etiology of externalizing psychopathology and highlight insensitive parenting as a potentially key developmental influence Using information from research on the neuroplasticity of selective attention and on the central role of successful parenting in child development , we developed and rigorously assessed a family-based training program design ed to improve brain systems for selective attention in preschool children . One hundred forty-one lower socioeconomic status preschoolers enrolled in a Head Start program were r and omly assigned to the training program , Head Start alone , or an active control group . Electrophysiological measures of children ’s brain functions supporting selective attention , st and ardized measures of cognition , and parent-reported child behaviors all favored children in the treatment program relative to both control groups . Positive changes were also observed in the parents themselves . Effect sizes ranged from one-quarter to half of a st and ard deviation . These results lend impetus to the further development and broader implementation of evidence -based education programs that target at-risk families Our previous work demonstrated that abacus-based mental calculation ( AMC ) , a traditional Chinese calculation method , could help children improve their math abilities ( e.g. basic arithmetical ability ) and executive function ( e.g. working memory ) . This study further examined the effects of long-term AMC training on math ability in visual-spatial domain and the task switching component of executive function . More importantly , this study investigated whether AMC training modulated the relationship between math abilities and task switching . The participants were seventy 7-year-old children who were r and omly assigned into AMC and control groups at primary school entry . Children in AMC group received 2-hour AMC training every week since primary school entry . On the contrary , children in the control group had never received any AMC training . Math and task switching abilities were measured one year and three years respectively after AMC training began . The results showed that AMC children performed better than their peers on math abilities in arithmetical and visual-spatial domains . In addition , AMC group responded faster than control group in the switching task , while no group difference was found in switch cost . Most interestingly , group difference was present in the relationships between math abilities and switch cost . These results implied the effect of AMC training on math abilities as well as its relationship with executive function We assessed the immediate effects of two universal , first- grade preventive interventions on the proximal targets of poor achievement , concentration problems , aggression , and shy behaviors , known early risk behaviors for later substance use/abuse , affective disorder , and conduct disorder . The classroom-centered ( CC ) intervention was design ed to reduce these early risk behaviors by enhancing teachers ' behavior management and instructional skills , whereas the family-school partnership ( FSP ) intervention was aim ed at improving parent-teacher communication and parental teaching and child behavior management strategies . Over the course of first and second grade s , the CC intervention yielded the greatest degree of impact on its proximal targets , whereas the FSP 's impact was somewhat less . The effects were influenced by gender and by preintervention levels of risk . Analyses of implementation measures demonstrated that greater fidelity to the intervention protocol s was associated with greater impact on behavior ratings and on achievement scores , thus providing some evidence of specificity in the effect of the interventions This study examined whether rumination subtypes ( brooding and reflection ) mediated prospect i ve associations between temperament ( negative emotionality and positive emotionality ) and depressive symptoms in a community sample of 423 adolescents . Effortful control and sex were examined as potential moderators of the mediated pathway . Youth self-reported negative emotionality ( NE ) , positive emotionality ( PE ) , and effortful control ( EC ) at age 12 ; brooding and reflection subtypes of rumination at age 14 ; and depressive symptoms at ages 12 , 14 , and 15 . Hierarchical linear regression analyses indicated that , controlling for initial levels of depressive symptoms , high NE , but not low PE , predicted increases in depressive symptoms from age 12 to age 15 . Brooding , but not reflection , mediated the association between NE and depressive symptoms . Neither sex nor EC moderated either indirect pathway in the mediated model . The results confirm and extend previous findings on the association between affective and cognitive vulnerability factors in predicting depressive symptoms in adolescence Fast Track is a multisite , multicomponent preventive intervention for young children at high risk for long-term antisocial behavior . Based on a comprehensive developmental model , intervention included a universal-level classroom program plus social skills training , academic tutoring , parent training , and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten . At the end of Grade 1 , there were moderate positive effects on children 's social , emotional , and academic skills ; peer interactions and social status ; and conduct problems and special-education use . Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline , warmth/positive involvement , and involvement with the school . Evidence of differential intervention effects across child gender , race , site , and cohort was minimal OBJECTIVE To evaluate the effectiveness and mechanisms of Hitkashrut , a " common elements " co-parent training ( PT ) program for early intervention with preschoolers ( 3 - 5 years of age ) at risk for conduct problems ( CP ) . METHOD A r and omized controlled trial with 140 participants in PT and 69 in a minimal intervention control group . The primary outcome ( presence of CP ) was assessed at pre-intervention , post-intervention , and 1-year follow-up . Callous-unemotional traits , effortful control , parental distress , negative/inconsistent parenting , and couple relationship quality were assessed at pre- and post-intervention , whereas callous-unemotional traits and effortful control were also assessed in the PT group at follow-up . Retention was 87.1 % at post-intervention and 60 % at follow-up . Hitkashrut incorporated evidence -based components of established PT programs into a culturally adapted protocol . The facilitators were trained and supervised psychologists working in Israel 's Educational Psychology Services . RESULTS Intervention effect ( Cohen 's d ) was large at post-intervention ( ES = .76 , p < .001 ) , and an additional medium effect was found at follow-up ( ES = 0.63 , p < .001 ) . Parallel post-intervention and follow-up intervention effects were also found in the degree of clinical ly significant improvements . Effects of the intervention on callous-unemotional traits ( ES = 0.85 , p < .001 ) and effortful control ( ES = 0.47 , p < .001 ) were maintained at follow-up . Follow-up improvement in CP was mediated by improvements in parental practice s and distress . CONCLUSIONS Hitkashrut 's implementation and subsequent dissemination in real-world setting s demonstrates the potential effectiveness of common elements programs to promote innovations within service-delivery systems . Improvements in dispositional variables and the mediated follow-up effect support theoretical cascade models that emphasize early developmental malleability and the growing preventive effects of PT 's facilitated parental changes on disruptive developmental trajectories . Clinical trial registration information - The effect of a " common elements " co-parent training program ( called ' Hitkashrut ' ) on conduct in preschoolers at risk for conduct problems ; http://www.anzctr.org.au ; ACTRN12612000148875 OBJECTIVE To examine the extent to which self-regulatory capacities , measured behaviorally at ages 3 and 5 years , were linked to rapid weight gain in children from age 3 to 12 years . Self-regulation failure , or the inability to control an impulse or behavior , has been implicated as a mechanism in the development of overweight . DESIGN Prospect i ve longitudinal cohort study . SETTING Home and laboratory-based setting s in 10 sites across the United States . PARTICIPANTS Data were drawn from 1061 children as part of the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development . Main Exposure Self-regulatory capacity was measured in 2 behavioral protocol s ; children participated in a self-control procedure at age 3 years and a delay of gratification procedure at age 5 years . MAIN OUTCOME MEASURES Age- and sex-specific body mass index ( BMI ) z scores were calculated based on measured BMI at 6 points . RESULTS Mixed-modeling analyses were used to examine differences in the rate of weight gain over time based on the extent to which children exhibited the ability to self-regulate in the behavioral procedures . Compared with children who showed high self-regulation in both behavioral protocol s at ages 3 and 5 years , children who exhibited a compromised ability to self-regulate had the highest BMI z scores at each point and the most rapid gains in BMI z scores over the 9-year period . Effects of pubertal status were also noted for girls . CONCLUSION Self-regulation failure in early childhood may predispose children to excessive weight gain through early adolescence Objective To identify family and child characteristics that put toddlers at risk of injuries . Design A prospect i ve cohort study . Setting This study was based on the Norwegian Mother and Child Cohort Study , conducted by the Norwegian Institute of Public Health . Participants The study sample consisted of 26 087 children and their mothers . Outcome measures Family and child characteristics measured before or at 18 months of age were investigated as potential predictors of hospital-attended injuries that occurred between 18 and 36 months of age . Results In the multivariable analysis , younger maternal age ( OR 0.93 , 95 % CI 0.86 to 1.00 ) , financial problems ( OR 1.18 , 95 % CI 1.01 to 1.39 ) , maternal mental distress ( OR 1.09 , 95 % CI 1.03 to 1.16 ) , having older siblings ( OR 1.22 , 95 % CI 1.08 to 1.39 ) , increased gestational age at birth ( OR 1.04 , 95 % CI 1.00 to 1.07 ) and male gender ( OR 1.26 , 95 % CI 1.11 to 1.42 ) were risk factors for hospital-attended injuries . Children with impaired gross motor development had a decreased risk of injury ( OR 0.65 , 95 % CI 0.42 to 0.99 ) , whereas those with impaired fine motor development had an increased risk ( OR 1.55 , 95 % CI 1.22 to 1.97 ) . Shyness was a protective factor ( OR 0.92 , 95 % CI 0.86 to 0.98 ) . Children with three reported attention problems had a slightly increased risk of hospital-attended injuries ( OR 1.33 , 95 % CI 1.02 to 1.72 ; p=0.035 ) ; otherwise , behaviour was not a significant risk factor . Conclusions This study demonstrated that a wide variety of factors were in play as predictors of injuries in young children . Both child-related factors ( gender , gestational age at birth , child motor development , shyness and attention ) and familial factors ( having older siblings , maternal age , financial difficulties and maternal mental health problems ) were associated with injuries in toddlers This study tested whether individual executive function ( EF ) tasks were better characterized as formative or reflective indicators of the latent construct of EF . EF data that were collected as part of the Family Life Project ( FLP ) , a prospect i ve longitudinal study of families who were recruited at the birth of a new child ( N = 1,292 ) , when children were 3 , 4 , and 5 years old . Vanishing tetrad tests were used to test the relative fit of models in which EF tasks were used as either formative or reflective indicators of the latent construct of EF in the prediction of intellectual ability ( at Age 3 ) , attention-deficit hyperactivity disorder symptoms ( at Ages 3 to 5 years ) , and academic achievement ( at kindergarten ) . Results consistently indicated that EF tasks were better represented as formative indicators of the latent construct of EF . Next , individual tasks were combined to form an overall measure of EF ability in ways generally consistent with formative ( i.e. , creating a composite mean score ) and reflective ( i.e. , creating an EF factor score ) measurement . The test-retest reliability and developmental trajectories of EF differed substantially , depending on which overall measure of EF ability was used . In general , the across-time stability of EF was markedly higher when represented as a factor score versus composite score . Results are discussed with respect to the ways in which the statistical representation of EF tasks can exert a large impact on inferences regarding the developmental causes , course , and consequences of EF BACKGROUND Temperamental characteristics emerge early in life and can shape children 's development , adjustment and behaviour . We aim ed to investigate the association between early infant temperament and later childhood psychiatric disorder in a community sample . METHODS This prospect i ve , population -based study used data from the Avon Longitudinal Study of Parents and Children ( ALSPAC ) . In a sample of 7318 children , we investigated whether temperamental characteristics assessed at the ages of 6 months and 24 months are associated with an independent diagnosis of psychiatric disorder ascertained at age 7 years . RESULTS After adjusting for confounders , temperamental characteristics assessed at 6 and 24 months of age were associated with psychiatric disorder at age 7 years . In particular , intensity of emotional reaction at age 6 months was associated with later disorder ( adjusted odds ratio = 1.56 ; 95 % confidence interval 1.19 , 2.04 ; P = 0.002 ) . These associations were stronger in girls and in those children with high levels of intensity at both 6 and 24 months of age . CONCLUSIONS Temperamental characteristics involving high levels of emotional intensity within the first year of life are longitudinally associated with psychiatric disorder in mid-childhood , suggesting that the roots of psychiatric disorder may , in some cases , lie very early in life The working memory ( WM ) processes that underlie young children 's ( ages 6 - 8 years ) mathematical precociousness were examined . A battery of tests that assessed components of WM ( phonological loop , visual-spatial sketch pad , and central executive ) , naming speed , r and om generation , and fluency was administered to mathematically precocious and average-achieving children . The results showed that ( a ) precocious children performed better on executive processing , inhibition , and naming speed tasks than did average-achieving children , although the two groups were statistically comparable on measures of the phonological loop and visual-spatial sketch pad , and ( b ) the executive component of WM predicted mathematical accuracy independent of chronological age , reading , inhibition , and naming speed . The results support the notion that the executive system is an important predictor of children 's mathematical precociousness and that this system can operate independent of individual differences in the phonological loop , inhibition , and reading in predicting mathematical accuracy Abstract Temperament and psychopathology are intimately related ; however , research on the prospect i ve associations between positive emotionality , defined as a child ’s positive mood states and high engagement with the environment , and psychopathology is inconclusive . We examined the longitudinal relation between positive emotionality and internalizing problems in young children from the general population . Furthermore , we explored whether executive functioning mediates any observed association . Within a population -based Dutch birth cohort , we observed positive emotionality in 802 children using the laboratory temperament assessment battery at age 3 years . Child behavior checklist ( CBCL ) internalizing problems ( consisting of Emotionally Reactive , Anxious/Depressed , and Withdrawn scales ) were assessed at age 6 years . Parents rated their children ’s executive functioning at ages 4 years . Children with a lower positive emotionality at age 3 had a higher risk of withdrawn problems at age 6 years ( OR = 1.20 per SD decrease in positive emotionality score , 95 % CI : 1.01 , 1.42 ) . This effect was not explained by preexisting internalizing problems . This association was partly mediated by more problems in the shifting domain of executive functioning ( p < 0.001 ) . We did not find any relation between positive emotionality and the CBCL emotionally reactive or anxious/depressed scales . Although the effect sizes were moderate , our results suggest that low levels of positive emotionality at preschool age can result in children ’s inflexibility and rigidity later in life . The inflexibility and rigidity are likely to affect the child ’s drive to engage with the environment , and thereby lead to withdrawn problems . Further research is needed to replicate these findings This study examines the relations of higher order ( i.e. , abstract ) thinking ( HOT ) skills to specific domains of social competence in Black boys ( n = 108 ) attending publicly sponsored prekindergarten ( pre-K ) programs . Data for the study were collected as part of the National Center for Early Development and Learning ( NCEDL ) Multi-State Study , a national , longitudinal study examining the quality and outcomes in a representative sample of publicly sponsored pre-K programs in six states ( N = 240 ) . Pre-K and kindergarten teachers rated r and omly selected children on measures of abstract thinking , self-regulation , and social functioning at the beginning and end of each school year . Applying structural equation modeling , compared with earlier time points , HOT measured in the fall of kindergarten significantly predicted each of the domains of social competence in the spring of kindergarten , with the exception of peer social skills , while controlling for general cognitive ability . Results suggest that early intervention to improve HOT may be an effective and more focused approach to address concerns about Black boys ' early social competencies in specific domains and potentially reduce the risk of later social difficulties Impairments in executive function have been documented in school-age children with mathematical learning difficulties . However , the utility and specificity of preschool executive function abilities in predicting later mathematical achievement are poorly understood . This study examined linkages between children 's developing executive function abilities at age 4 and children 's subsequent achievement in mathematics at age 6 , 1 year after school entry . The study sample consisted of a regionally representative cohort of 104 children followed prospect ively from ages 2 to 6 years . At age 4 , children completed a battery of executive function tasks that assessed planning , set shifting , and inhibitory control . Teachers completed the preschool version of the Behavior Rating Inventory of Executive Function . Clinical and classroom measures of children 's mathematical achievement were collected at age 6 . Results showed that children 's performance on set shifting , inhibitory control , and general executive behavior measures during the preschool period accounted for substantial variability in children 's early mathematical achievement at school . These associations persisted even after individual differences in general cognitive ability and reading achievement were taken into account . Findings suggest that early measures of executive function may be useful in identifying children who may experience difficulties learning mathematical skills and concepts . They also suggest that the scaffolding of these executive skills could potentially be a useful additional component in early mathematics education Despite knowledge of early pathways to conduct problems , few preventive interventions are specifically design ed to modify disruptive behavior in toddlerhood . One potential prevention target is proactive and positive parenting , which is associated with reduced risk of conduct problems in preschoolers . This r and omized trial with 120 low-income 2-year-old boys examined whether a brief family-centered intervention that reduces disruptive behavior ( D. Shaw , T. Dishion , L. Supplee , F. Gardner , & K. Arnds , 2006 ) also leads to increases in proactive and positive parenting . It also explored whether change in parenting predicts change in disruptive behavior . In the intervention group , proactive and positive parenting skills increased among parents of 3-year-olds . Change in proactive and positive parenting of 2- to 3-year-old toddlers correlated with change in child disruptive behavior , although the mediation effect of positive parenting was of only borderline significance . Findings suggest that even within a brief and multifaceted preventive intervention , change in proactive parenting skills contributes modestly but significantly to change in child problem behavior OBJECTIVE : Executive functioning and excess weight have been associated in cross-sectional and prospect i ve studies , but mechanisms explaining this relationship are unclear . The current study aim ed to further explore the longitudinal relationship between executive functioning and changes in body weight and to determine whether binge eating behaviors mediate this relationship . METHODS : Community-based girls ( N = 2450 ) were assessed by using the behavioral measure of planning , Mazes subtest , and a parent-report measure of impulsivity at age 10 ; a self-report measure of binge eating at ages 10 , 12 , and 14 ; and investigator-measured BMI annually between ages 10 and 16 . Regression and bootstrapping analyses explored the relations among age 10 impulsivity and planning , age 12 and age 14 binge eating frequency , and age 10 to 16 BMI changes . RESULTS : Age 10 impulsivity and planning each independently predicted age 10 to 16 BMI changes , after accounting for demographics , verbal comprehension , and BMI at age 10 ( Ps < .001 ) . Binge eating tendencies at age 12 mediated the relation between age 10 impulsivity and age 10 to 16 BMI changes , after controlling for demographics , verbal comprehension , binge eating frequency , and BMI at age 10 ( indirect effect estimate = 0.0007 ; 95 % confidence interval = 0.0001–0.0020 ) . CONCLUSIONS : Results support the hypothesis that poorer executive functioning predicts weight gain from middle childhood through adolescence in girls , and that this effect may be partially explained by binge-eating behaviors in early adolescence Identifying childhood precursors for depression has been challenging and yet important for underst and ing the rapid increase in the rate of depression among adolescent girls . This study examined the prospect i ve relations of preadolescent girls ' emotion regulation and parenting style with depressive symptoms . Participants were 225 children and their biological mothers recruited from a larger longitudinal community study . Girls ' observed positive and negative emotion during a conflict resolution task with mothers , their ability to regulate sadness and anger , and their perception of parental acceptance and psychological control were assessed at age 9 . Depressive symptoms were assessed by self-report at ages 9 and 10 . The results indicated interactions between child emotion characteristics and parenting in predicting later depression . Specifically , low levels of positive emotion expression predicted higher levels of depressive symptoms in the context of moderate to high parental psychological control . Low levels of sadness regulation were predictive of high levels of depressive symptoms in the context of low to moderate parental acceptance . Findings from this study support the hypothesis that the prospect i ve association between vulnerabilities in emotion regulation and depression are moderated by the caregiving environment The relation of self-regulation measured prior to school entry to developing math and reading ability in prekindergarten through the second grade was examined in a prospect i ve longitudinal sample of 1,292 children and families in predominantly rural and low-income communities in 2 regions of high poverty in the United States . Direct assessment s of executive function , effortful control , and stress response physiology ( indexed by resting levels of cortisol and alpha amylase obtained from saliva ) were measured at child age 48 months and parents and teachers reported on children 's effortful control using temperament rating scales at child age approximately 60 months . Math and reading ability , as measured by the Woodcock-Johnson III applied problems and letter-word subtests , respectively , were measured at prekindergarten through the second grade . Effects for self-regulation measures were seen primarily for initial level and to some extent growth in both mathematics and reading , even when controlling for family demographic characteristics that represent relevant selection factors into higher levels of both self-regulation and academic achievement . These effects persisted for mathematics but not for reading with the inclusion of child cognitive abilities , vocabulary , and speed of processing measured in prekindergarten , concurrent with the first time point for the academic measures . Results are interpreted as indicating a role for self-regulation in learning ability generally , likely through support for attention and reasoning abilities that are most specific to the assessment of mathematics in this analysis . Implication s for instruction and for assessment and the best ways to support the development of early math and reading ability for children at risk for school failure are discussed Thirty preschoolers from low-income families participated in a 12-month intervention programme , funded by Sure Start , which engaged them in scaffolded educational activities delivered at home by their mothers . Immediately following the programme , the intervention group outperformed matched controls in tests of academic knowledge , receptive vocabulary , and inhibitory control , but not short-term memory or theory of mind . Teachers ' ratings of children 's capabilities upon school entry favoured the intervention group , especially in terms of listening , responding , writing , mathematics , and personal/social skills . Superior inhibitory control , short-term memory , and numerical skills were associated with higher ratings whereas theory of mind made a unique , negative contribution to responding . We discuss the implication s of these findings for efforts to nurture the development of cognitive self-regulation and school readiness during early childhood Studied the effectiveness of parent and teacher training as a selective prevention program for 272 Head Start mothers and their 4-year-old children and 61 Head Start teachers . Fourteen Head Start centers ( 34 classrooms ) were r and omly assigned to ( a ) an experimental condition in which parents , teachers , and family service workers participated in the prevention program ( Incredible Years ) or ( b ) a control condition consisting of the regular Head Start program . Assessment s included teacher and parent reports of child behavior and independent observations at home and at school . Construct scores combining observational and report data were calculated for negative and positive parenting style , parent-teacher bonding , child conduct problems at home and at school , and teacher classroom management style . Following the 12-session weekly program , experimental mothers had significantly lower negative parenting and significantly higher positive parenting scores than control mothers . Parent-teacher bonding was significantly higher for experimental than for control mothers . Experimental children showed significantly fewer conduct problems at school than control children . Children of mothers who attended 6 or more intervention sessions showed significantly fewer conduct problems at home than control children . Children who were the " highest risk " at baseline ( high rates of noncompliant and aggressive behavior ) showed more clinical ly significant reductions in these behaviors than high-risk control children . After training , experimental teachers showed significantly better classroom management skills than control teachers . One year later the experimental effects were maintained for parents who attended more than 6 groups . The clinical ly significant reductions in behavior problems for the highest risk experimental children were also maintained . Implication s of this prevention program as a strategy for reducing risk factors leading to delinquency by promoting social competence , school readiness , and reducing conduct problems are discussed PURPOSE In the present study , the authors examined the prospect i ve associations among early language skills , behavioral regulation skills , and 2 aspects of school-age social functioning ( adaptability and social skills ) . METHOD The study sample consisted of children with and without a familial risk for dyslexia . The authors analyzed the relations among children 's language ( at age 2;6 [ years;months ] and age 5;0 ) , behavioral regulation skills ( at age 5;0 ) , and social functioning ( at age 8;0 ) using structural equation modeling . Subgroups of children with respect to language and behavioral regulation skills ( at age 5;0 ) were identified through the use of mixture modeling . RESULTS Among at-risk children , behavioral regulation skills mediated the association between early language skills and social outcomes . A subgroup of children with poor regulatory and weak language skills scored lower in adaptability , whereas a subgroup having only poor language skills ( with normal behavioral regulation ) did not differ from a group with age-appropriate skills . CONCLUSIONS The present findings indicate that behavioral regulation skills play an important role in predicting social outcomes among children at risk for language difficulties . Furthermore , it is suggested that various aspects of social functioning may be influenced differently by self-regulation skills and that predictive relationships vary with the degree of language development deficits and accompanying risks Adolescent family adversity is a considerable adaptive challenge in an increasingly turbulent developmental period . Using data from a prospect i ve population cohort of 2230 Dutch adolescents , we tested risk-buffering interactions between adolescent family adversity and self-regulation capacities on mental health . We used two adaptive self-regulation capacities that could allow adolescents to manage relatively well with family adversity : ( 1 ) parent-reported effortful control , and ( 2 ) an attentional flexibility ( in this case , set-shifting ) task . Adolescent family adversity was associated with internalizing problems and externalizing problems . The risk-buffering effects of effortful control were found for externalizing problems but not for internalizing problems . There were no risk-buffering effects of attentional flexibility on both types of mental health problems . Effortful control is likely to benefit adolescents ’ ability to channel their frustrations in adaptive ways in the presence of family adversity . Additionally , ( attentional ) set-shifting tasks might have a limited predictive value for risk-buffering research Despite recent research indicating that 1 of the pivotal times for identifying pathways to early conduct problems is the toddler period , few family-based preventive interventions have been specifically design ed to modify child disruptive behavior during this age period . This r and omized trial tested the effectiveness of the Family Check-Up in sustaining maternal involvement and preventing the exacerbation of child conduct problems among 120 at-risk toddler-age boys , half of whom were r and omly assigned to a treatment condition . The intervention was associated with reductions in disruptive behavior and greater maternal involvement and was particularly effective for children at greater risk for a persistent trajectory of conduct problems . The results are discussed in relation to other preventive interventions for young children AIMS To examine how adolescents ' inattentive behaviour , together with parental smoking patterns , predicts smoking initiation by age 14 . DESIGN , SETTING S : A prospect i ve , longitudinal study : baseline at ages 11 - 12 , follow-up at age 14 . A population -based sample of Finnish twins , born 1983 - 1987 , with parents and classroom teachers as additional informants . Two groups were formed , allocating the co-twins of each family into separate groups : the study sample and a replication sample . PARTICIPANTS Twin individuals ( n = 4552 ) , aged 11 - 12 at baseline and 14 ( average 14.04 years ) at follow-up . MEASUREMENTS At baseline , inattentiveness was assessed with the Multidimensional Peer Nomination Inventory ( MPNI , Teacher Form ) and parental smoking with individual question naires completed by each twins ' parents ; at the age 14 follow-up , adolescent smoking was assessed with a self-report question naire . FINDINGS At age 14 , 57 % reported never having smoked , 34 % had experimented with cigarettes and 9 % were current smokers . Inattentiveness and parental smoking additively predicted both experimental and current smoking in adolescence . The effects were independent of each other . CONCLUSIONS The risk related to inattentiveness itself is high , but in combination with the effects of parental smoking , the probability of current smoking can rise as high as 38 % , compared with 5 % without these two risk factors . For prevention purpose s , parental commitment to non-smoking should be emphasized BACKGROUND School readiness , conceptualized as three components including emotional self-regulation , social competence , and family/school involvement , as well as absence of conduct problems play a key role in young children 's future interpersonal adjustment and academic success . Unfortunately , exposure to multiple poverty-related risks increases the odds that children will demonstrate increased emotional dysregulation , fewer social skills , less teacher/parent involvement and more conduct problems . Consequently intervention offered to socio-economically disadvantaged population s that includes a social and emotional school curriculum and trains teachers in effective classroom management skills and in promotion of parent-school involvement would seem to be a strategic strategy for improving young children 's school readiness , leading to later academic success and prevention of the development of conduct disorders . METHODS This r and omized trial evaluated the Incredible Years ( IY ) Teacher Classroom Management and Child Social and Emotion curriculum ( Dinosaur School ) as a universal prevention program for children enrolled in Head Start , kindergarten , or first grade classrooms in schools selected because of high rates of poverty . Trained teachers offered the Dinosaur School curriculum to all their students in bi-weekly lessons throughout the year . They sent home weekly dinosaur homework to encourage parents ' involvement . Part of the curriculum involved promotion of lesson objectives through the teachers ' continual use of positive classroom management skills focused on building social competence and emotional self-regulation skills as well as decreasing conduct problems . Matched pairs of schools were r and omly assigned to intervention or control conditions . RESULTS Results from multi-level models on a total of 153 teachers and 1,768 students are presented . Children and teachers were observed in the classrooms by blinded observers at the beginning and the end of the school year . Results indicated that intervention teachers used more positive classroom management strategies and their students showed more social competence and emotional self-regulation and fewer conduct problems than control teachers and students . Intervention teachers reported more involvement with parents than control teachers . Satisfaction with the program was very high regardless of grade levels . CONCLUSIONS These findings provide support for the efficacy of this universal preventive curriculum for enhancing school protective factors and reducing child and classroom risk factors faced by socio-economically disadvantaged children The role of temperamental characteristics in accelerated and decelerated weight gain in normal infants has not been investigated previously except for differences in activity . The present study drew a r and om sample of 200 normal infants from a largely middle-class private practice . It found 24 infants who gained 30 or more percentile points in weight for length determinations between 6 and 12 months of age and 25 who lost 20 percentile points or more . These growth data were compared with contemporaneous findings on the Infant Temperament Question naire . Those gaining the most had significantly more difficult temperament ratings ( p < 0.05 ) and were perceived by their mothers as “ more difficult than average ” ( p < 0.001 ) . Infants with the most decelerated growth were not temperamentally different from the general sample . Negative mood rather than low activity was the specific characteristic distinguishing the infants gaining the most ( p = 0.006 ) . Clinical experience would suggest that fussy infants are fed more to quiet them Abstract Results are reported of a 2-year prospect i ve , longitudinal study of young children representing a general population sample . Temperament and home environment characteristics measured at age 2 and again at 3 are used to predict behavioral problems at age 3 . The findings indicate that the temperament characteristics of poor adaptability and high intensity of emotional expression more powerfully predict behavior problems than do indices of the interpersonal and material home environment . Beyond the influence of temperament , marital discord operates rather selectively in boys to heighten the risk for a poor outcome Forty-four Head Start classrooms were r and omly assigned to enriched intervention ( Head Start REDI- Research -based , Developmentally Informed ) or " usual practice " conditions . The intervention involved brief lessons , " h and s-on " extension activities , and specific teaching strategies linked empirically with the promotion of : ( a ) social-emotional competencies and ( b ) language development and emergent literacy skills . Take-home material s were provided to parents to enhance skill development at home . Multi method assessment s of three hundred and fifty-six 4-year-old children tracked their progress over the course of the 1-year program . Results revealed significant differences favoring children in the enriched intervention classrooms on measures of vocabulary , emergent literacy , emotional underst and ing , social problem solving , social behavior , and learning engagement . Implication s are discussed for developmental models of school readiness and for early educational programs and policies Childhood sedentary behavior has been linked to increased obesity risk . Prior work has identified associations between sedentary behavior , executive function ( EF ) , and sleep . This study tested the hypothesis that reduced sleep duration may adversely impact EF and lead to increased childhood sedentary behavior . Southern California schoolchildren participating in the school-based health promotion program Pathways to Health ( N=709 ) were assessed annually from 4th through 6th grade s ( 2010 - 2013 ) on self-report measures of sedentary behavior , sleep duration , and executive function . A series of path models were specified treating average nightly sleep duration and weekend wake/bed-time shift at 4th grade as predictors of 6th grade sedentary behavior . Four EF subdomains were tested as potential mediators of longitudinal associations at 5th grade . Significant associations between average nightly sleep duration , EF and sedentary behavior were identified ( p<0.05 ) , adjusting for participant gender , physical activity , SES , ethnicity , program group assignment , and the presence/absence of parental screen time rules . Fifth grade overall EF (p<0.05)- and in particular the subdomains of inhibitory control ( p<0.05 ) and organization of material s (p<0.01)-significantly mediated the relationship between 4th grade sleep duration and 6th grade sedentary behavior ( p<0.05 ) . Furthermore , delay of weekend bed- or wake-times relative to weekdays was prospect ively associated with decreased overall EF ( p<0.05 ) , but not increased sedentary behavior ( p=0.35 for bed-time delay ; p=0.64 for wake-time delay ) , irrespective of average nightly sleep duration . Findings suggest that sleep promotion efforts may reduce children 's sedentary behavior both directly and indirectly through changes in EF This study investigated the longitudinal impact of maltreatment parameters on personality processes and maladjustment and prospect i ve relationships between personality trajectory classes and subsequent maladjustment outcomes . The sample involved maltreated ( n = 249 ) and nonmaltreated ( n = 200 ) children followed longitudinally between ages 6 and 10 . Growth mixture modeling indicated multifinality in personality development depending on the risk status ( i.e. , maltreated vs. nonmaltreated ) . Two trajectory classes of ego resiliency were identified for maltreated children : those who showed a declining trajectory exhibited greater maladjustment . In contrast , three trajectory classes of ego control were identified for nonmaltreated children ; the subgroups showing increases in ego undercontrol or dramatic changes from high ego undercontrol to high ego overcontrol exhibited poor adjustment . Experiencing multiple maltreatment subtypes and physical/sexual abuse were related to higher levels of ego undercontrol and externalizing symptomatology , whereas early onset of maltreatment was associated with the low and decreasing trajectory of ego resiliency and higher levels of internalizing symptomatology . The findings suggest that ego resiliency and ego control , personality processes related to self-regulation , may be important factors in identifying distinct pathways to later personality disorders as well as pathways to resilient functioning The present short-term longitudinal study examined the concurrent and prospect i ve relations among executive functioning ( i.e. , working memory and cognitive flexibility ) , coping ( primary and secondary control coping ) , and depressive symptoms in children . Participants were 192 children between 9 and 15 years old ( M age = 12.36 years , SD = 1.77 ) recruited from the community . Youth were individually administered neuropsychological measures of executive functioning and intelligence and completed self-report measures of executive dysfunction , coping , and depressive symptoms in small groups ; the latter two measures were completed again 4 months later ( Time 2 [ T2 ] ) . Linear regression analyses were used to examine direct associations among executive functions , coping , and depressive symptoms , and a bootstrapping procedure was used to test indirect effects of executive functioning on depressive symptoms through coping . Significant prospect i ve relations were found between working memory measured at Time 1 ( T1 ) and both primary and secondary control coping measured at T2 , controlling for T1 coping . T1 cognitive flexibility significantly predicted T2 secondary control coping , controlling for T1 coping . Working memory deficits significantly predicted increases in depressive symptoms 4 months later , controlling for T1 depressive symptoms . Bootstrap analyses revealed that primary and secondary control coping each partially mediated the relation between working memory and depressive symptoms ; secondary control coping partially mediated the relation between cognitive flexibility and depressive symptoms . Coping may be one pathway through which deficits in executive functioning contribute to children 's symptoms of depression Objective : Little research has addressed the relationships among infant temperament , eating styles and obesity risk . To address this gap , we tested whether infant temperament and eating patterns at the age of 1 year are associated with a greater increase in st and ardized weight status , and greater obesity risk at 6 years of age . Design : A secondary , prospect i ve analysis of the Colorado Adoption Study was conducted . The main predictor variables were infant temperament ( that is , emotionality , activity , attention span-persistence , reaction to food and soothability ) and eating domains ( that is , reactivity to food , predictable appetite and distractability at mealtime ) at the age of 1 year , along with the body mass index ( BMI ) of biological mothers . The outcome measures were child weight and height ( length ) assessed at ages 1 through 6 years , from which weight-for-length and BMI were computed along with the st and ardized indexes ( z-scores ) and percentiles . Overweight/obesity status was computed at each year as well . Participants : A primarily White sample of 262 boys and 225 girls , assessed at ages 1 through 6 years , along with their mothers . Results : Among boys , greater attention span-persistence was associated with reduced st and ardized weight status gain ( β=−0.15 , P<0.05 ) and reduced obesity risk ( odds ratio (OR)=0.46 , P=0.06 ) . Among girls , greater soothability and negative reaction to food were associated with greater st and ardized weight status gain ( β=0.19 , P<0.01 ; and β=0.16 , P<0.05 , respectively ) and increased obesity risk ( OR=3.72 , P=0.03 ; and OR=2.81 , P=0.08 , respectively ) . Biological mothers ’ obesity status predicted obesity risk in boys ( OR=3.07 , P=0.01 ) and girls ( OR=5.94 , P=0.03 ) . Conclusions : Male infants with less attention span , and female infants with greater soothability or a more negative food reaction , showed greater increases in st and ardized weight and were more likely to be overweight/obese at the age of 6 years . The role of infant temperament in pediatric obesity onset warrants greater research Objectives : We tested whether early childhood risk exposures are related to weight gain in adolescence and evaluate an underlying mechanism , self-regulatory behavior , for the risk-obesity link . Methods : Cumulative risk exposure to 9 sociodemographic ( eg , poverty ) , physical ( eg , subst and ard housing ) , and psychosocial ( eg , family turmoil ) stressors was assessed in 244 nine-year-old children . BMI was calculated at age 9 and then 4 years later . At age 9 , children ’s ability to delay gratification as an index of self-regulatory behavior was assessed . Path analyses were then estimated to evaluate our mediational model ( Cumulative risk → Self-regulation → BMI ) over a 4-year period in a prospect i ve , longitudinal design . Results : Nine-year-old children exposed to a greater accumulation of multiple risk factors show larger gains in adiposity over the next four year period , net of their initial BMI . These gains in BMI during early adolescence are largely accounted for by deteriorated self-regulatory abilities among children facing more cumulative risks . Conclusions : Early childhood risk exposure leads to larger gains in BMI in adolescence . Given the importance of childhood adiposity to the development of obesity later in life , underst and ing the underlying mechanisms that link early experience to weight gain is an essential task . Deficiencies in self-regulation in response to chronic stress appears to be an important agent in the obesity epidemic Objective . To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years . Methods . We conducted , in public and private care setting s in Denver , Colorado , a r and omized , controlled trial with 3 arms , ie , control , paraprofessional visits , and nurse visits . Home visits were provided from pregnancy through child age 2 years . We invited 1178 consecutive , low-income , pregnant women with no previous live births to participate , and we r and omized 735 ; 85 % were unmarried , 47 % Mexican American , 35 % white non-Mexican American , 15 % black , and 3 % American Indian/Asian . Outcomes consisted of maternal reports of subsequent pregnancies , participation in education and work , use of welfare , marriage , cohabitation , experience of domestic violence , mental health , substance use , and sense of mastery ; observations of mother-child interaction and the home environment ; tests of children 's language and executive functioning ; and mothers ' reports of children 's externalizing behavior problems . Results . Two years after the program ended , women who were visited by paraprofessionals , compared with control subjects , were less likely to be married ( 32.2 % vs 44.0 % ) and to live with the biological father of the child ( 32.7 % vs 43.1 % ) but worked more ( 15.13 months vs 13.38 months ) and reported a greater sense of mastery and better mental health ( st and ardized scores [ mean = 100 , SD = 10 ] of 101.25 vs 99.31 and 101.21 vs 99.16 , respectively ) . Paraprofessional-visited women had fewer subsequent miscarriages ( 6.6 % vs 12.3 % ) and low birth weight newborns ( 2.8 % vs 7.7 % ) . Mothers and children who were visited by paraprofessionals , compared with control subjects , displayed greater sensitivity and responsiveness toward one another ( st and ardized score [ mean = 100 , SD = 10 ] of 100.92 vs 98.66 ) and , in cases in which the mothers had low levels of psychologic re sources at registration , had home environments that were more supportive of children 's early learning ( score of 24.63 vs 23.35 ) . Nurse-visited women reported greater intervals between the births of their first and second children ( 24.51 months vs 20.39 months ) and less domestic violence ( 6.9 % vs 13.6 % ) and enrolled their children less frequently in preschool , Head Start , or licensed day care than did control subjects . Nurse-visited children whose mothers had low levels of psychologic re sources at registration , compared with control group counterparts , demonstrated home environments that were more supportive of children 's early learning ( score of 24.61 vs 23.35 ) , more advanced language ( score of 91.39 vs 86.73 ) , superior executive functioning ( score of 100.16 vs 95.48 ) , and better behavioral adaptation during testing ( score of 100.41 vs 96.66 ) . There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies , women 's educational achievement , use of substances , use of welfare , or children 's externalizing behavior problems . Conclusions . Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years , but their first-born children were not statistically distinguishable from their control group counterparts . Nurse-visited mothers and children continued to benefit from the program 2 years after it ended . The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic re sources The aim of this study was to determine whether the extent of improvement in self-regulation achieved between ages 4 and 6 years is associated with the level of behavioral problems later in childhood . Participants were 4-year-old children ( n = 510 ) attending preschools in South Australia . Children 's level of self-regulation was assessed using the parent-completed Devereux Early Childhood Assessment when children were aged 4 , 5 , and 6 . Children 's level of behavioral problems was assessed using total , internalizing , and externalizing scores on parent- and teacher-rated Strengths and Difficulties Question naires ( SDQs ) when children were 6 years old . R and om effects regression was used to describe the changes to children 's self-regulation between 4 and 6 years . Linear regression models were then used to determine the strength of the association between the extent of self-regulation improvement and level of behavioral problems . Greater improvement in self-regulation , adjusted for family characteristics and baseline self-regulation scores , was associated with lower levels of parent- ( B = -3.57 , 95 % confidence interval [ CI ] [ -4.49 , -2.65 ] ) and teacher-rated SDQ total difficulties scores at 6 years ( B = -2.42 , 95 % CI [ -3.50 , -1.34 ] ) . These effects remained after adjustment for level of parent-rated behavioral problems at 4 years . Similar effects were found for internalizing and externalizing scores at age 6 years . The results highlight the importance of improvements in self-regulation from 4 - 6 years for childhood behavioral problems during the early school years . Children with lower levels of improvement in self-regulation early in life are at risk for higher levels of behavioral problems both at home and at school Background : Cluster r and omised trials ( CRTs ) are increasingly used to assess the effectiveness of health interventions . Three main analysis approaches are : cluster-level analyses , mixed-models and generalized estimating equations ( GEEs ) . Mixed models and GEEs can lead to inflated type I error rates with a small number of clusters , and numerous small- sample corrections have been proposed to circumvent this problem . However , the impact of these methods on power is still unclear . Methods : We performed a simulation study to assess the performance of 12 analysis approaches for CRTs with a continuous outcome and 40 or fewer clusters . These included weighted and unweighted cluster-level analyses , mixed-effects models with different degree-of-freedom corrections , and GEEs with and without a small- sample correction . We assessed these approaches across different values of the intraclass correlation coefficient ( ICC ) , numbers of clusters , and variability in cluster sizes . Results : Unweighted and variance-weighted cluster-level analysis , mixed models with degree-offreedom corrections , and GEE with a small- sample correction all maintained the type I error rate at or below 5 % across most scenarios , whereas uncorrected approaches lead to inflated type I error rates . However , these analyses had low power ( below 50 % in some scenarios ) when fewer than 20 clusters were r and omized , with none reaching the expected 80 % power . Conclusion : Small- sample corrections or variance-weighted cluster-level analyses are recommended for the analysis of continuous outcomes in CRTs with a small number of clusters . The use of these corrections should be incorporated into the sample size calculation to prevent studies from being underpowered BACKGROUND While temperamental characteristics have been related to the onset of cannabis use , it is not clear at what point(s ) along the trajectory from early onset of tobacco use ( EOT ) to early onset of cannabis use ( EOC ) these characteristics exert their impact . This study examined if ( 1 ) temperamental characteristics predispose to EOT that on its turn predisposes to EOC , and ( 2 ) temperament moderates the importance of EOT on the progression to EOC . METHODS Data from 1848 ( 83 % ) participants in the TRacking Adolescents ' Individual Lives Survey ( TRAILS ) , a prospect i ve population study of Dutch adolescents , were analyzed . We used parent-reports on the Early Adolescent Temperament Question naire to assess the dimensions of high-intensity pleasure , frustration , effortful control , shyness and fearfulness at age 10 - 12 . EOT and EOC were defined as use at least once before the ages of 12 and 13 years , respectively , assessed by means of self-reports . We performed mediation and moderation analyses in Mplus . RESULTS High levels of high-intensity pleasure predisposed to entrance in the trajectory from EOT to EOC . Once tobacco use had been initiated at early age , low levels of shyness and high levels of high-intensity pleasure increased the risk of progression to EOC . CONCLUSIONS Besides a common liability for EOT and EOC based on temperament , the risk of transition from tobacco to cannabis use is modified by temperamental characteristics . Differences in interplay with other risk factors may explain the impact of temperament on distinct points along the substance use trajectory Previous studies indicate that and rogen levels and certain psychological characteristics such as anger and impulsivity are related to the development and maintenance of aggression . Further studies are required to analyze the potential predictor role of the interaction of said factors on aggressive behavior . 90 nine-year-old children ( 44 boys and 46 girls ) were assessed in relation to their levels of physical , verbal and indirect aggression , using a peer-rating technique . Testosterone and and rostenedione levels were analyzed using an enzymoimmunoassay technique in saliva sample s. Anger ( state and trait ) and anger control were measured using the STAXI-NA , and impulsivity was measured through the MFF-20 . A General Linear Model revealed that sex was the best predictor for aggression measures , with boys scoring higher than girls in physical , verbal and indirect aggression ; after sex , testosterone was found to be the best predictor ( in a positive sense ) of all three types of aggressive behavior studied . In addition to observing a main effect of and rostenedione on physical and verbal aggression , a ' state anger * and rostenedione ' interaction was found to predict these types of aggression , with and rostenedione acting as a moderator ( inhibitor ) of the effects of anger on these behaviors ; also , a ' state anger*testosterone ' interaction was found to predict verbal aggression . The results support the idea that , after sex , and rogens constitute a biological marker to be taken into consideration in relation to individual differences in aggressive behavior . It is possible that at the age of 9 , testosterone tends to increase aggression , while and rostenedione tends to moderate ( inhibit ) the effects of anger on aggression |
2,380 | 30,662,248 | Fluid knee benefits and indications : Knees with hydraulic or pneumatic swing resistance are indicated for active walkers , permitting increased walking comfort , speed , and symmetry .
Microprocessor knee benefits : Compared with nonmicroprocessor knees : a ) With respect to self-report indices and measures , microprocessor knees are indicated to reduce stumbles , falls , and associated frustrations as well as the cognitive dem and s of ambulation .
b ) With respect to self-report indices and measures , microprocessor knees are indicated to increase confidence while walking , self-reported mobility , satisfaction , well-being , and quality of life .
c ) With respect to physical performance indices and measures , microprocessor knees are indicated to increase self-selected walking speed , walking speed on uneven terrain , and metabolic efficiency during gait .
Microprocessor knees for limited community ambulators : Among limited community ambulators , microprocessor knees are indicated to enable increases in level ground walking speed and walking speed on uneven terrain while substantially reducing uncontrolled falls and increasing both measured and perceived balance . | Introduction This guideline was developed to present the evidence and provide clinical recommendations on prosthetic knee selection for unilateral amputation at the knee disarticulation or transfemoral level .
Methods The guideline is based upon the best available evidence as it relates to prosthetic knee selection after unilateral knee disarticulation or transfemoral amputation . | The functional differences between persons with amputation who are classified as Medicare Functional Classification Level (MFCL)-2 and -3 include the abilities to walk at various cadences and to negotiate environmental barriers outside the home . This study compared the effect of active microprocessor control and passive mechanical control of the prosthetic knee on function and safety in 17 subjects with transfemoral amputation ( 8 MFCL-2 and 9 MFCL-3 ) . Assessed functional tasks included hill and stair descent , an attentional dem and task , and an obstacle course . Self-reported measures included concentration , multitasking ability , and numbers of stumbles and falls . Active knee control was associated with significant improvements ( p < 0.05 ) in hill and stair gait , speed ( hills , obstacle course , and attentional dem and task ) , and ability to multitask while walking for both cohorts . MFCL-2 subjects also reported a significant reduction ( p < 0.01 ) in uncontrolled falls . Over the study , 50 % of MFCL-2 subjects and 33 % of MFCL-3 subjects transitioned to a higher MFCL . Results suggest that active knee control improves function and reduces the frequency of adverse events in a population that is at risk for falls . Use of active knee control may allow persons with amputation to exp and their functional domain , transition to a higher MFCL , and access additional prosthetic options Microprocessor-controlled prosthetic knees are cl aim ed to improve gait efficiency in transfemoral ( TF ) amputees . This hypothesis was tested in a prospect i ve r and omized crossover trial that compared the Mauch SNS knee and the C-Leg microprocessor-controlled knee in eight TF amputees . The subjects were given a 3-month acclimation period in each knee . Then , their net oxygen cost ( mL/kg/m ) was measured while they walked overground at four speeds in r and om order : 0.8 m/s , 1.0 m/s , 1.3 m/s , and self-selected walking speed ( SSWS ) . The C-Leg caused small reductions in net oxygen cost that were not statistically significant compared with the Mauch SNS at any of the walking speeds ( p > 0.190 ) . Subjects chose higher SSWSs with the C-Leg compared with the Mauch SNS ( mean + /- st and ard deviation = 1.31 + /- 0.12 m/s vs 1.21 + /- 0.10 m/s , respectively , p = 0.046 ) but did not incur higher oxygen costs ( p = 0.270 ) , which suggests greater efficiency only at their SSWS OBJECTIVE To evaluate the gait of transfemoral amputee patients using a prosthesis with a 4-bar linkage knee joint with either a mechanical swing phase control ( Otto Bock 3R20 ) or a pneumatic swing phase control ( Tehlin knee ) . DESIGN R and omized cross-over trial . SETTING Rehabilitation Department of a university hospital in The Netherl and s. PATIENTS Twenty-eight subjects with unilateral transfemoral amputation for reasons other than chronic vascular disease ; ages between 16 and 65 years and familiar with the use of the Otto Bock 3R20 knee . SELECTION PROCEDURE a consecutive sample . INTERVENTION The Otto Bock 3R20 was used by the subjects before they entered the study . The patients changed to the Tehlin knee at r and om either after 1 or 2 assessment s with the Otto Bock 3R20 . MAIN OUTCOME MEASURES Temporal and kinematic variables in gait analysis ( speed recordings were taken before and after the equipment for the measurements of the other parameters was placed on the patients ) . Subjective scores for comfortable and fast ambulation were obtained by means of 2 question naires . Question naire A consisted of multiple choice questions ( maximum score : 5 ) and questions using an 8-point rating scale ( maximum score : 7 ) . In question naire B , the patient was asked to compare the present prosthesis with the previous one . RESULTS Fast walking speed in gait analysis was higher with the Tehlin knee than with the 3R20 ( without equipment 95 % confidence interval ( CI ) .02-.09 m/sec , with equipment CI .04-.11 ) , while comfortable walking speed was not higher with the Tehlin knee ( without equipment CI -.20-.20 m/sec , with equipment CI .00-.05 ) . Symmetry of walking as regards swing phase duration was closer to 100 % with the Tehlin knee than with the 3R20 ( comf . walking CI 4 % to 19 % , fast walking CI 7 % to 17 % ) . Knee joint range of motion during swing phase was smaller with the Tehlin knee than with the 3R20 ( comf . walking CI 1.8 degrees-8.7 degrees , fast walking CI 2.0 degrees-9.5 degrees ) . Knee flexion duration during swing phase was shorter for the Tehlin knee than for the 3R20 at fast walking speed ( CI 6 - 46msec ) , while knee flexion duration from and to 10 degrees flexion was shorter for the Tehlin knee at comfortable speed ( CI 18 - 67msec ) and fast speed ( CI 20 - 64msec ) . In question naire A the amputees reported the Tehlin knee to be better for fast walking ( part A1 CI .01-.52 , part A2 CI .13-.98 ) and in question naire B for both comfortable and fast walking The C-Leg ( Otto Bock , Duderstadt , Germany ) is a microprocessor-controlled prosthetic knee that may enhance amputee gait . This intrasubject r and omized study compared the gait biomechanics of transfemoral amputees wearing the C-Leg with those wearing a common noncomputerized prosthesis , the Mauch SNS ( Ossur , Reykjavik , Icel and ) . After subjects had a 3-month acclimation period with each prosthetic knee , typical gait biomechanical data were collected in a gait laboratory . At a controlled walking speed ( CWS ) , peak swing phase knee-flexion angle decreased for the C-Leg group compared with the Mauch SNS group ( 55.2 degrees + /- 6.5 degrees vs 64.41 degrees + /- 5.8 degrees , respectively ; p = 0.005 ) ; the C-Leg group was similar to control subjects ' peak swing knee-flexion angle ( 56.0 degrees + /- 3.4 degrees ) . Stance knee-flexion moment increased for the C-Leg group compared with the Mauch SNS group ( 0.142 + /- 0.05 vs 0.067 + /- 0.07 N"m , respectively ; p = 0.01 ) , but remained significantly reduced compared with control subjects ( 0.477 + /- 0.1 N"m ) . Prosthetic limb step length at CWS was less for the C-Leg group compared with the Mauch SNS group ( 0.66 + /- 0.04 vs 0.70 + /- 0.06 m , respectively ; p = 0.005 ) , which result ed in increased symmetry between limbs for the C-Leg group . Subjects also walked faster with the C-Leg versus the Mauch SNS ( 1.30 + /- 0.1 vs 1.21 + /- 0.1 m/s , respectively ; p = 0.004 ) . The C-Leg prosthetic limb vertical ground reaction force decreased compared with the Mauch SNS ( 96.3 + /- 4.7 vs 100.3 + /- 7.5 % body weight , respectively ; p = 0.0092 ) Johansson JL , Sherrill DM , Riley PO , Bonato P , Herr H : A clinical comparison of variable-damping and mechanically passive prosthetic knee devices . Am J Phys Med Rehabil 2005;84:563–575 . Objective : Although variable-damping knee prostheses offer some improvements over mechanically passive prostheses to transfemoral amputees , there is insufficient evidence that such prostheses provide advantages at self-selected walking speeds . In this investigation , we address this question by comparing two variable-damping knees , the hydraulic-based Otto Bock C-leg and the magnetorheological-based Össur Rheo , with the mechanically passive , hydraulic-based Mauch SNS . Design : For each prosthesis , metabolic data were collected on eight unilateral amputees walking at self-selected speeds across an indoor track . Furthermore , kinetic , kinematic , and electromyographic data were collected while walking at self-selected speeds across a 10-m walkway in a laboratory . Results : When using the Rheo , metabolic rate decreases by 5 % compared with the Mauch and by 3 % compared with the C-leg . Furthermore , for the C-leg and Rheo knee devices , we observe biomechanical advantages over the mechanically passive Mauch . These advantages include an enhanced smoothness of gait , a decrease in hip work production , a lower peak hip flexion moment at terminal stance , and a reduction in peak hip power generation at toe-off . Conclusion : The results of this study indicate that variable-damping knee prostheses offer advantages over mechanically passive design s for unilateral transfemoral amputees walking at self-selected ambulatory speeds , and the results further suggest that a magnetorheological-based system may have advantages over hydraulic-based design OBJECTIVE To evaluate differences in function , performance , and preference between mechanical and microprocessor prosthetic knee control technologies . DESIGN A-B-A-B reversal design . SETTING Home , community , and laboratory environments . PARTICIPANTS Twenty-one unilateral , transfemoral amputees . INTERVENTION Mechanical control prosthetic knee versus microprocessor control prosthetic knee ( Otto Bock C-Leg ) . MAIN OUTCOME MEASURES Stair rating , hill rating and time , obstacle course time , divided attention task accuracy and time , Amputee Mobility Predictor score , step activity , Prosthesis Evaluation Question naire score , Medical Outcomes Study 36-Item Short-Form Health Survey score , self-reported frequency of stumbles and falls , and self-reported concentration required for ambulation . RESULTS Stair descent score , hill descent time , and hill sound-side step length showed significant ( P<.01 ) improvement with the C-Leg . Users reported a significant ( P<.05 ) decrease in frequency of stumbles and falls , frustration with falling , and difficulty in multitasking while using the microprocessor knee . Subject satisfaction with the C-Leg was significantly ( P<.001 ) greater than the mechanical control prosthesis . CONCLUSIONS The study population showed improved performance when negotiating stairs and hills , reduced frequency of stumbling and falling , and a preference for the microprocessor control C-Leg as compared with the mechanical control prosthetic knee This study investigated energy expenditure and obstacle course negotiation between the C-leg ® and various non-microprocessor control ( NMC ) prosthetic knees and compared a quality of life survey ( SF-36v2 ™ ) of use of the C-leg ® to national norms . Thirteen subjects with unilateral limb loss ( 12 with trans-femoral and one with a knee disarticulation amputation ) participated in the study . The mean age was 46 years , range 30 – 75 . Energy expenditure using both the NMC and C-leg ® prostheses was measured at self-selected typical and fast walking paces on a motorized treadmill . Subjects were also asked to walk through a st and ardized walking obstacle course carrying a 4.5 kg ( 10 lb ) basket and with h and s free . Finally , the SF-36v2 ™ was completed for subjects while using the C-leg ® . Statistically significant differences were found in oxygen consumption between prostheses at both typical and fast paces with the C-leg ® showing decreased values . Use of the C-leg ® result ed in a statistically significant decrease in the number of steps and time to complete the obstacle course . Scores on a quality of life index for subjects using the C-leg ® were above the mean for norms for limitation in the use of an arm or leg , equal to the mean for the general United States population for the physical component score and were above this mean for the mental component score . Based on oxygen consumption and obstacle course findings , the C-leg ® when compared to the NMC prostheses may provide increased functional mobility and ease of performance in the home and community environment . Question naire results suggest a minimal quality of life impairment when using a C-leg ® for this cohort of individuals with amputation Objective : To compare the gait of amputees wearing conventionally damped pneumatic swing-phase control knees and microchip-controlled Intelligent Prostheses . Design : Crossover trial . Setting : An amputee rehabilitation centre in a teaching hospital . Participants : Ten established unilateral transfemoral prosthetic users were asked to participate in the trial ; all agreed . Interventions : The amputees were assessed wearing pneumatic swing-phase control knees and then with the Intelligent Prosthesis . Main outcome measures : Oxygen consumption while walking at different speeds on a treadmill , video-recording of gait assessed by a panel and temporal – spatial parameters of gait whilst walking at slow , fast or normal speeds in a gait laboratory . Results : Mean oxygen cost for all subjects at 0.69 m/s was 0.33 ml/kg.m with the conventional limb and 0.30 ml/kg.m with the Intelligent Prosthesis ( p–0.01 ) . At 1.25 m/s the mean oxygen cost for the conventional limb was 0.24 ml/kg.m and for the Intelligent Prosthesis was 0.22 ml/kg.m ( not significant ) . The ANOVA analysis showed that oxygen cost was similar at normal walking speeds but increased more at lower speeds for the pneumatic swing-phase control leg compared to the Intelligent Prosthesis ( p<0.02 ) . There were no significant differences in subjective gait evaluation or temporal and spatial gait parameters . Conclusion : At lower speeds oxygen cost was lower with the Intelligent Prosthesis . Gait analysis detected no significant changes between the two legs OBJECTIVE To compare objective cognitive performance and perception of cognitive burden during walking tasks using 2 different prosthetic knees : a computerized hydraulic knee ( Otto Bock C-leg ) and a noncomputerized hydraulic knee ( Ossur Mauch SNS ) . DESIGN Two-group crossover trial , with participants r and omly assigned to order of prosthesis . Participants completed assessment s under 2 conditions , a self-selected speed walk and a controlled speed walk , on 2 separate occasions ( precrossover , postcrossover ) . SETTING Veterans Health Administration hospital . PARTICIPANTS Eight transfemoral amputees . INTERVENTION Computerized versus noncomputerized prosthetic knee . MAIN OUTCOME MEASURES Objective cognitive performance measures included verbal fluency ( Controlled Oral Word Association Test , Category Test ) , attention and working memory ( serial subtraction ) , and walking speed during cognitive tasks . Measures of perceived cognitive burden included subjective attentional requirements of walking and cognitive tasks and subjective general cognitive burden of prosthesis . RESULTS There were no significant differences in objective cognitive performance on any task between prostheses , nor did walking speed vary by prosthesis during the free-speed walk . Participants reported that walking required less attention while wearing the C-leg and that the C-leg was less of a cognitive burden than the noncomputerized prosthesis . CONCLUSIONS In nondem and ing walking conditions with experienced amputees , participants reported that the more costly C-leg required less cognitive attention than the noncomputerized knee . However , this subjective experience did not translate to improved performance on neuropsychologic screening instruments or on walking speed . Noncomputerized prostheses may be adequate for a majority of amputees , and further research is needed to identify particular groups of amputees ( ie , new amputees , amputees with complex physical or cognitive dem and s ) who may benefit from computerized prostheses In this study , the influence of different prosthetic alignments and components on oxygen consumption and the important biomechanical characteristics of the normal gait pattern of leg amputees was investigated . With 15 transtibial and 12 transfemoral amputees , the oxygen consumption during walking on a treadmill was analyzed and biomechanical parameters during walking on even ground at a self-selected speed were defined . The amputation of all patients was caused by trauma . Variations of the prosthetic alignment affect the energy consumption of transfemoral amputees more significantly than that of transtibial amputees . Comparison of different prosthetic feet worn by transtibial amputees did not show significant differences regarding metabolic parameters . Compared with conventional hydraulic knee controls , the oxygen consumption of transfemoral amputees provided with an electronically controlled hydraulic knee joint is reduced . All investigated variations can be clearly characterized by the sagittal moments acting on the joints of the prosthetic limb during gait |
2,381 | 31,392,098 | Conclusions Findings show that a co-dependence between changes in kinematics and a decrease in performance , which stems from central and peripheral fatigue , is a contributing factor of injury in baseball pitchers .
A large percentage of baseball pitchers exhibit pain or soreness in either their elbow or shoulder , or both at some point in a season .
Initially , kinematic changes occur that could maintain performance , but may increase joint and tissue loading .
Performance decreased with elevated pitch counts and innings thrown , and pitching further into games or the season . | Background Fatigue in baseball pitchers is a process linked to lowered physical and mental performance , injury , and changes in kinematics .
Numerous studies have associated fatigue with overuse , high ball velocities , lack of rest time , poor mechanics , and degree of self-satisfaction .
The aim of this study was to systematic ally review the literature to identify a theoretical framework for the relationship between outcomes and the manifestation of fatigue on baseball pitching . | Background Joint pain is thought to be an early sign of injury to a pitcher . Objective To evaluate the association between pitch counts , pitch types , and pitching mechanics and shoulder and elbow pain in young pitchers . Study Design Prospect i ve cohort study . Methods Four hundred and seventy-six young ( ages 9 to 14 years ) baseball pitchers were followed for one season . Data were collected from pre- and postseason question naires , injury and performance interviews after each game , pitch count logs , and video analysis of pitching mechanics . Generalized estimating equations and logistic regression analysis were used . Results Half of the subjects experienced elbow or shoulder pain during the season . The curveball was associated with a 52 % increased risk of shoulder pain and the slider was associated with an 86 % increased risk of elbow pain . There was a significant association between the number of pitches thrown in a game and during the season and the rate of elbow pain and shoulder pain . Conclusions Pitchers in this age group should be caution ed about throwing breaking pitches ( curveballs and sliders ) because of the increased risk of elbow and shoulder pain . Limitations on pitches thrown in a game and in a season can also reduce the risk of pain . Further evaluation of pain and pitching mechanics is necessary INTRODUCTION A recent US Major League Baseball ( MLB ) rule change requires baseball pitchers to deliver pitches within 12 s. PURPOSE S To examine the effect of three between-pitch rest intervals on throwing performance during a simulated seven-inning game and muscle damage during postgame recovery . DESIGN A r and omized counterbalanced study . METHODS Seven intercollegiate pitchers threw 15 pitches per inning for seven innings with rest interval trials of 8 , 12 , and 20 s between pitches and 5 min between innings . Pitchers threw aim ed fastballs at their best effort . Trials were separated by ≥2 wk . RESULTS Progressive decreases in pitching speed and accuracy below baseline ( first inning of 20-s trial ) occurred after fourth inning during the 8-s and 12-s trials , but not the 20-s trial . Plasma creatine kinase elevated 48 h later for the 8-s and 12-s trials ( + 105 % and + 75 % , P < 0.01 ) , but not the 20-s trial ( + 26 % , no significance ) . A transient interleukin (IL)-6 surges immediately after the game for the 8- and 12-s trials ( + 265 % , + 128 % , P < 0.01 ) above baseline . IL-6 reversed below the level of 20-s trial at 48 h after game , whereas IL-10 increased significantly above the level of 20-s trial . CONCLUSIONS Under the same pitching load , decreasing rest interval from 20 to 12 s or less results in an early-onset performance loss during a game and increases in muscle damage and inflammation for more than 2 d after a game . Our data do not favor the current rule change in concern of keeping musculoskeletal health of pitchers 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 CONTEXT Fatigue could contribute to ankle-sprain injuries during sport , particularly for individuals with chronic ankle instability ( CAI ) . OBJECTIVE To examine whether adults with or without CAI develop fatigue at similar rates when performing ankle exercises at the same relative effort level and whether these groups differ in their subjective perceptions of fatigue . DESIGN Controlled laboratory study . SETTING Biomechanics research laboratory . PATIENTS OR OTHER PARTICIPANTS A total of 11 volunteers with CAI ( 1 man , 10 women ; age = 23.5 ± 3.0 years , height = 168.0 ± 11.2 cm , mass = 64.3 ± 13.5 kg ) were recruited for the unstable-ankle group , and 11 volunteers matched for age , height , mass , and sex ( 1 man , 10 women ; age = 24.1 ± 2.1 years , height = 169.5 ± 9.7 cm , mass = 62.3 ± 9.7 kg ) were recruited as control participants . INTERVENTION(S ) Localized muscle fatigue ( LMF ) was induced in the ankle of the dominant limb using a custom fatigue protocol . Plantar-flexion and dorsiflexion exertions were completed at a rate of 12 cycles per minute at isotonic loads equal to 70 % and 30 % , respectively , of individual maximal voluntary isometric strength . Intermittent measures of maximal voluntary isometric strength and ratings of perceived exertion ( RPEs ) were obtained . MAIN OUTCOME MEASURE(S ) We compared isometric-strength measures and RPE scores at each observation time ( prefatigue and at 4 , 8 , 12 , and 16 minutes into the fatigue protocol ) and the group correlations between changes in strength and changes in RPE scores . RESULTS Based on ankle-strength measures , the 2 test groups developed LMF at similar rates when exercising at equivalent levels of relative effort . The 2 groups also reported similar levels of discomfort as fatigue progressed . CONCLUSIONS The rate of LMF development at the ankle and the associated perception of fatigue did not differ between adults with or without CAI Abstract Freeston , J , Adams , R , Ferdin and s , RED , and Rooney , K. Indicators of throwing arm fatigue in elite adolescent male baseball players : A r and omized crossover trial . J Strength Cond Res 28(8 ) : 2115–2120 , 2014—Throwing carries an inherent risk of injury that worsens in the presence of arm fatigue . The purpose of this study was to identify markers that could facilitate the early detection of this type of fatigue , by comparing the response to bouts of throwing-specific and running-based exercise . Thirteen elite junior male baseball players were tested twice , 7 days apart with a r and omized crossover design . They were assessed for shoulder proprioception , maximal throwing velocity , and throwing accuracy before and after a 10-minute bout of either throwing-specific ( THROW ) or general ( RUN ) exercise . Maximal throwing velocity was reduced similarly after both THROW and RUN bouts ( −1.0 ± 0.4 vs. −0.6 ± 0.2 m·s−1 , respectively ; p ⩽ 0.05 ) ; however , accuracy was only reduced after THROW ( 7.6 ± 3.4 cm ; p ⩽ 0.05 ) . Arm soreness increased significantly more after THROW than RUN ( 3.5 ± 0.7 vs. 1.4 ± 0.5 km·h−1 , respectively ; p ⩽ 0.05 ) . Shoulder proprioception did not change after either exercise bout . The results suggest that throwing velocity is an indicator of general fatigue , whereas throwing accuracy and arm soreness are markers of arm fatigue . Shoulder proprioception does not seem to be a sensitive marker of either type of fatigue . Throwing velocity should be monitored to gauge overall fatigue levels , whereas accuracy and arm soreness should be closely monitored to gauge arm fatigue and throwing-induced injury risk Abstract Oliver , GD , Weimar , WH , and Henning , LE . Effects of a simulated game on muscle activation in youth baseball pitchers . J Strength Cond Res 30(2 ) : 415–420 , 2016—It is generally accepted that playing with fatigue is a primary predictor of injury in youth baseball because muscular fatigue is believed to alter mechanics during the arm cocking and acceleration phases . Therefore , the purpose of this study was to quantitatively describe gluteal and upper extremity muscle activations in youth baseball pitchers during a simulated game . Twenty-three youth baseball players ( 11.2 ± 0.8 years ; 151.4 ± 8.7 cm ; 47.5 ± 10.8 kg ) participated . Data were collected through a Delsys Bagnoli–8-channel electromyography system . Single differential electrodes ( interelectrode distance : 10 mm ) were attached to the bilateral gluteus maximus and medius and throwing side latissimus dorsi , lower trapezius , and serratus anterior and upper trapezius . After warm-up , participants were instructed to throw r and omly provided game situations over a regulation distance ( 46 feet ; 14.02 meters ) to a catcher . Three , 4-seam fastballs for strikes , thrown in the first and last innings of the simulated game were selected for analysis . A multivariate analysis of variance revealed no statistically significant differences in muscle activity at the 3 phases of the throw , between first and last innings of the simulated game with an observed power of 0.274 ( phase 1 : foot contact to maximum shoulder external rotation ) , 0.297 ( phase 2 : maximum shoulder external rotation to ball release ) , and 0.226 ( phase 3 : ball release to maximum shoulder internal rotation ) . Examining muscle activations as a pitcher approaches fatigue provides information on how long a pitcher can perform before mechanical alterations occur . Although this study did not reveal significant changes , it did reiterate the fact that pitch counts may be working in possibly preventing a youth pitcher throwing to fatigue BACKGROUND Overexertion caused by increased pitch counts can evoke protective biomechanical responses signified by decreased ball velocity , such as reduced throwing arm kinematics and kinetics . Among skilled pitchers , overexertion may not always present ball velocity decrements , because compensatory throwing biomechanics aid in maintaining peak ball velocity although lowering physiologic stress . METHODS Nineteen pitchers ( collegiate and elite high school ) , r and omly crossed over to pitch two simulated games at ± 25 % of their desired stride length , were recorded by an eight-camera motion capture system ( 240 Hz ) integrated with two piezoelectric force plates ( 960 Hz ) and a professional model radar gun . HR , self-reported exertion scores , blood glucose and lactate , salivary biomarkers , peak linear h and and fastball velocities were examined . Repeated- measures ANOVA as well as independent and pairwise t-tests examined significant differences ( P ≤ 0.05 ) . RESULTS Shortened strides reduced mean pitching HR by 11.1 bpm ( P < 0.001 ) , improved recovery capacity by 5.76 % ( P = 0.012 ) , and lowered salivary cortisol from baseline ( P = 0.001 ) . Physiologic stress elevated with greater strides , because salivary alpha amylase was significantly elevated from baseline ( P = 0.011 ) with no improvements evidence d in pitching HR or recovery capacity . Linear h and and ball velocities remained equivalent between stride conditions . CONCLUSION Stride length can affect physical exertion without disrupting ball velocity , where shortening strides can plausibly respond to competitive exertion in baseball pitchers . Current pitch count st and ards and radar velocity accounts have not been proven efficacious in predicting exertion in professional and collegiate baseball , where biomechanical compensations arise to maintain ball velocity . In some instances , compensatory adaptations may be pathomechanic where future research identifying injurious movement patterns can advance injury prevention in professional baseball |
2,382 | 21,059,602 | Overall , statistically significant improvements were noted in knowledge , attitude , and help-seeking behaviour .
CONCLUSION Although evidence exists that school-based programmes to prevent suicide among adolescents improve knowledge , attitudes , and help-seeking behaviours , no evidence yet exists that these prevention programmes reduce suicide rates . | OBJECTIVE To assess the effectiveness of middle and high school-based suicide prevention curricula . | This study employed a self-report question naire in a Solomon four-groups design to assess the efficacy of suicide intervention classes in achieving their instructional objectives . Because adolescents are often the first to know of a peer 's suicidal thoughts or plans , the goal of the classes was to increase the likelihood that students who come into contact with potentially suicidal peers can more readily identify them and will be consistently inclined to take responsible action on their behalf . Students who participated in the classes as compared to controls showed significant gains in relevant knowledge about suicidal peers and significantly more positive attitudes toward help seeking and intervening with troubled peers . Results of this study will be used to strengthen components of the lessons aim ed at enhancing the likelihood of performance of responsible interventions The effectiveness of a school-based primary prevention psychological program is assessed in the present study . The program was design ed to ( a ) improve students ' distress-coping , ( b ) prepare them as " gatekeepers " with regard to self-destructive behavior of peers and ( c ) assess the program 's face validity and social validity . The program was primarily based on cognitive-behavioral modification principles , procedures and techniques . Two hundred and thirty-seven students , drawn from six homeroom grade eight classes were r and omly assigned to experimental and control ( no intervention ) conditions . The program consisted of seven units passed during twelve weekly one-hour sessions . Overall , the program had a positive effect on attitudes , emotions , knowledge and awareness of distress coping skills . In addition , it had some degree of face validity and social validity from the students ' vantage point . These results lend support to the feasibility of a cognitive-behavioral , school-based prevention program for students ' distress-coping enhancement OBJECTIVES We examined the effectiveness of the Signs of Suicide ( SOS ) prevention program in reducing suicidal behavior . METHODS Twenty-one hundred students in 5 high schools in Columbus , Ga , and Hartford , Conn , were r and omly assigned to intervention and control groups . Self-administered question naires were completed by students in both groups approximately 3 months after program implementation . RESULTS Significantly lower rates of suicide attempts and greater knowledge and more adaptive attitudes about depression and suicide were observed among students in the intervention group . The modest changes in knowledge and attitudes partially explained the beneficial effects of the program . CONCLUSIONS SOS is the first school-based suicide prevention program to demonstrate significant reductions in self-reported suicide attempts BACKGROUND Psycho-educational programs are among the most commonly applied suicide prevention approaches for young people . This study examined the effectiveness of these programs in a controlled study by assessing the effect on knowledge , attitudes , coping and hopelessness . METHOD Fourteen- to 18-year-old students were administered structured question naires before and after the program to assess the effect on knowledge , attitudes , coping and hopelessness . RESULTS The program had no effect on coping styles and levels of hopelessness . However , a positive effect on knowledge could be identified and an interaction effect of the program with gender on attitudes was also found . A negative impact of the program could not be found . Results indicated effects of gender and pre-test on knowledge , attitudes and coping . CONCLUSIONS The findings from this study suggest that psycho-educational programs in schools may influence knowledge about suicide and attitudes towards suicidal persons but may not affect the use of coping styles or levels of hopelessness 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 This study employed simulations of encounters with suicidal peers to assess the impact of classroom suicide response lessons . Students were asked to anonymously write how they would respond , and how concerned they would be in regard to two vignettes of troubled peers . On the posttest , students who had participated in the classes provided significantly more " tell an adult " responses than those in the control group , whereas no differences existed between the groups on the pretest . On both the pretest and posttest , all students expressed greater concern on the unambiguous vignette ( student said that he has been thinking about killing himself ) than on the ambiguous vignette ( student wrote an essay about final decisions ) ; and , overall , females expressed greater concern than males . These results provide evidence for the efficacy of the classes and the utility of the simulations for assessing their impact |
2,383 | 32,019,093 | We showed that low consumption of red meat and carbonated beverages , daily consumption of wine and high consumption of dishes seasoned with sofrito had beneficial effects on several QoL subscales .
By contrast , using olive oil as the main culinary fat , low consumption of commercial sweets and high consumption of nuts were associated with negative effects .
All the studies demonstrated significant improvements in overall QoL and /or its subscales after the interventions . | There is an ongoing need for solid evidence about the effects of healthy behaviors , and particularly diet , on the quality of life ( QoL ) among breast cancer survivors . | There is limited evidence on the association between adherence to guidelines for cancer survivors and health-related quality of life ( HRQoL ) . In a cross-sectional study of Korean breast cancer survivors , we examined whether adherence to the guidelines of the American Cancer Society ( ACS ) and World Cancer Research Fund/American Institute for Cancer Research ( WCRF/AICR ) for cancer survivors was related to levels of HRQoL , assessed by the Korean version of Core 30 ( C30 ) and Breast cancer module 23 ( BR23 ) of the European Organization for Research and Treatment of Cancer- Quality of Life Question naire ( EORTC-QLQ ) . We included a total of 160 women aged 21 to 79 years who had been diagnosed with breast cancer according to American Joint Committee on Cancer ( AJCC ) stages I to III and had breast cancer surgery at least six months before the interview . Increasing adherence to ACS guidelines was associated with higher scores of social functioning ( p for trend = 0.05 ) , whereas increasing adherence to WCRF/AICR recommendations was associated with higher scores of arm symptoms ( p for trend = 0.01 ) . These associations were limited to those with stage II or III cancer . Diet may be an important factor in relation to quality of life among Korean breast cancer survivors , however our findings warrant further prospect i ve studies to evaluate whether healthy diet improves survivors ’ quality of life PURPOSE To determine the effects of breast cancer-specific print material s and step pedometers on physical activity ( PA ) and quality of life ( QoL ) in breast cancer survivors . PATIENTS AND METHODS Breast cancer survivors ( N = 377 ) were r and omly assigned to receive one of the following : a st and ard public health recommendation for PA , previously developed breast cancer-specific PA print material s , a step pedometer , or a combination of breast cancer-specific print material s and step pedometers . The primary outcome was self-reported moderate/vigorous PA minutes per week . Secondary outcomes were QoL ( Functional Assessment of Cancer Therapy-Breast ) , fatigue , self-reported brisk walking , and objective step counts . Assessment s were conducted at baseline and postintervention ( 12 weeks ) . RESULTS Attrition was 10.3 % ( 39 of 377 ) . On the basis of linear mixed-model analyses , PA increased by 30 minutes/week in the st and ard recommendation group compared with 70 minutes/week in the print material group ( mean difference , 39 minutes/week ; 95 % CI = -10 to 89 ; d = 0.25 ; P = .117 ) , 89 minutes/week in the pedometer group ( mean difference , 59 minutes/week ; 95 % CI , 11 to 108 ; d = 0.38 ; P = .017 ) , and 87 minutes/week in the combined group ( mean difference , 57 minutes/week ; 95 % CI , 8 to 106 ; d = 0.37 ; P = .022 ) . For brisk walking minutes/week , all three intervention groups reported significantly greater increases than the st and ard recommendation group . The combined group also reported significantly improved QoL ( mean difference , 5.8 ; 95 % CI , 2.0 to 9.6 ; d = 0.33 ; P = .003 ) and reduced fatigue ( mean difference , 2.3 ; 95 % CI , 0.0 to 4.7 ; d = 0.25 ; P = .052 ) compared with the st and ard recommendation group . CONCLUSION Breast cancer-specific PA print material s and pedometers may be effective strategies for increasing PA and QoL in breast cancer survivors . A combined approach appears to be optimal . CLINICAL TRIAL REGISTRATION Clinical Trials.gov Identifier BACKGROUND Modifiable lifestyle factors , such as diet quality , could reduce inflammation and improve quality of life ( QOL ) in breast cancer survivors , but data are inconclusive . OBJECTIVE To determine whether diet quality , as measured by Healthy Eating Index-2010 ( HEI-2010 ) score , is associated with inflammation , health status , or functional outcomes affecting QOL in survivors of early-stage breast cancer . DESIGN This is a cross-sectional , secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before r and om assignment to a pilot nutritional intervention aim ed at reducing side effects of aromatase inhibitor treatment . PARTICIPANTS / SETTING Participants were 44 postmenopausal women with stage I to III endocrine receptor-positive breast cancer receiving outpatient care at a midwestern cancer center between November 2011 and October 2013 . MAIN OUTCOME MEASURES Primary outcomes were serum proinflammatory cytokines ( interleukin-6 [ IL-6 ] , IL-17 , and tumor necrosis factor-α receptor 2 [ TNFR-2 ] ) . Secondary outcomes included QOL measured by the Stanford Health and Disability Question naire and the Functional Assessment of Cancer Therapy-Breast with Endocrine Subscale . STATISTICAL ANALYSES PERFORMED Pearson correlation coefficients ( r ) and linear regression models were used to evaluate the relationship of dietary variables with inflammatory cytokines and QOL measures . RESULTS A higher overall HEI-2010 score ( healthier diet ) was associated with lower IL-6 ( r=-0.46 ; P=0.002 ) and TNFR-2 ( r=-0.41 ; P=0.006 ) ; however , associations were attenuated by body mass index ( BMI ) ( IL=6 [ r=-0.26 ; P=0.10 ] ; TNFR-2 [ r=-0.30 ; P=0.06 ] ) . In women with prior chemotherapy , a higher HEI-2010 score was strongly associated with lower IL-6 ( r=-0.67 ; P=0.009 ) and TNFR-2 ( r=-0.59 ; P=0.03 ) after BMI adjustment . There were no significant correlations between HEI-2010 score and QOL measures after adjustment for BMI . CONCLUSIONS These data suggest the need for more rigorous investigation into the relationship of diet quality , BMI , and inflammation in breast cancer survivors Obese breast cancer survivors have increased risk of recurrence and death compared to their normal weight counterparts . Rural women have significantly higher obesity rates , thus weight control intervention may be a key strategy for prevention of breast cancer recurrence in this population . This one-arm treatment study examined the impact of a group-based weight control intervention delivered through conference call technology to obese breast cancer survivors living in remote rural locations . The intervention included a reduced calorie diet incorporating prepackaged entrees and shakes , physical activity gradually increased to 225 min/week of moderate intensity exercise , and weekly group phone sessions . Outcomes included anthropomorphic , diet , physical activity , serum biomarker , and quality of life changes . Ninety-one percent of participants ( 31 of 34 ) attended > 75 % of intervention sessions and completed post-treatment data collection visits . At 6 months , significant changes were observed for weight ( −12.5 ± 5.8 kg , 13.9 % of baseline weight ) , waist circumference ( −9.4 ± 6.3 cm ) , daily energy intake ( −349 ± 550 kcal/day ) , fruits , and vegetables ( + 3.7 ± 4.3 servings/day ) , percent kcal from fat ( −12.6 ± 8.6 % ) , physical activity ( + 1235 ± 832 kcal/week ; all P values < 0.001 ) , as well as significant reductions in fasting insulin ( 16.7 % reduction , P = 0.006 ) , and leptin ( 37.1 % reduction , P < 0.001 ) . Significant improvements were also seen for quality of life domains including mood , body image , and sexuality . In conclusion , the intervention produced > 10 % weight loss as well as significant improvements across multiple endpoints . The group phone-based treatment delivery approach may help disseminate effective weight control intervention to hard-to-reach breast cancer survivors Objectives To support return to work ( RTW ) among cancer patients , a multidisciplinary rehabilitation programme was developed which combined occupational counselling with a supervised physical exercise programme during chemotherapy . The aim was to investigate RTW rates of cancer patients and to evaluate changes in work-related quality of life and physical outcomes . Design Longitudinal prospect i ve intervention study using a one-group design . Setting Two hospitals in the Netherl and s. Participants Of the eligible patients , 56 % participated ; 93 patients with a primary diagnosis of cancer receiving chemotherapy and on sick leave were included . Patients completed question naires on RTW , the importance of work , work ability ( WAI ) , RTW self-efficacy , fatigue ( MFI ) , and quality of life ( EORTC QLQ C-30 ) at baseline and 6 , 12 and 18 months follow-up . Before and after the exercise programme 1-repetition maximum ( 1RM ) muscle strength and cardiorespiratory fitness ( VO2 peak ) were assessed . Results Six months after the start of a multidisciplinary rehabilitation programme that combined occupational counselling with a supervised physical exercise programme , 59 % of the cancer patients returned to work , 86 % at 12 months and 83 % at 18 months . In addition , significant improvements ( p<0.05 ) in the importance of work , work ability , RTW self-efficacy , and quality of life were observed , whereas fatigue levels were significantly reduced . After completing the exercise programme , 1RM muscle strength was significantly increased but there was no improvement in VO2 peak level . Conclusions RTW rates of cancer patients were high after completion of the multidisciplinary rehabilitation programme . A multidisciplinary rehabilitation programme which combines occupational counselling with a supervised physical exercise programme is likely to result in RTW , reduced fatigue and increased importance of work , work ability , and quality of life Objective With increases in cancer survival , promotion of healthy lifestyle behaviors among survivors is receiving considerable attention . This study compared health behaviors among a large sample of Australian adult cancer survivors with an age- and sex-matched cohort of people with no cancer history . Methods Using the Australian National Health Survey , 968 cancer survivors were identified , and r and omly matched by age and sex to 5,808 respondents without a history of cancer . Six health behaviors were compared ( smoking , physical activity , servings of vegetables , servings of fruit , alcohol use , skin checks ) , along with overweight and obesity , using polytomous logistic regression analyses controlling for selected chronic conditions . Models were applied across both groups and by tumor site . Results Compared to the non-cancer comparison group , cancer survivors were significantly more likely to be current ( OR = 1.35 ) smokers , particularly those under 40 years ( OR = 1.69 ) , and more likely to have regular skin checks ( OR = 1.76 ) . Although not significant , there was consistent evidence that cancer survivors were slightly more likely to be overweight or obese ( p = 0.065 ) and have higher levels of alcohol consumption ( p = 0.088 ) . There was no evidence of differences between survivors and controls for levels of physical inactivity , vegetable consumption or fruit consumption . Women with a history of gynecological cancers were much more likely to be current smokers ( OR = 2.37 ) , while other differences by sex and cancer site were consistent with overall patterns . Cancer survivors were also significantly more likely to report having a range of co-morbid chronic medical conditions . Conclusion Given their increased risk of second cancers and co-morbid chronic conditions , the lack of difference in behavioral risk factors confirms the need for a focus on improving the health behaviors of cancer survivors . Collaborative chronic disease management models may be particularly appropriate in this regard 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 Background This pilot trial aim ed to study the feasibility and effects on quality of life ( QOL ) and well-being of short-term fasting ( STF ) during chemotherapy in patients with gynecological cancer . Methods In an individually-r and omized cross-over trial patients with gynecological cancer , 4 to 6 planned chemotherapy cycles were included . Thirty-four patients were r and omized to STF in the first half of chemotherapies followed by normocaloric diet ( group A;n = 18 ) or vice versa ( group B;n = 16 ) . Fasting started 36 h before and ended 24 h after chemotherapy ( 60 h-fasting period ) . QOL was assessed by the FACIT-measurement system . Results The chemotherapy-induced reduction of QOL was less than the Minimally Important Difference ( MID ; FACT-G = 5 ) with STF but greater than the MID for non-fasted periods . The mean chemotherapy-induced deterioration of total FACIT-F was 10.4 ± 5.3 for fasted and 27.0 ± 6.3 for non-fasted cycles in group A and 14.1 ± 5.6 for non-fasted and 11.0 ± 5.6 for fasted cycles in group B. There were no serious adverse effects . ConclusionS TF during chemotherapy is well tolerated and appears to improve QOL and fatigue during chemotherapy . Larger studies should prove the effect of STF as an adjunct to chemotherapy . Trial registration This trial was registered at clinical trials.gov : NCT01954836 Purpose Regular exercise and healthy eating are routinely recommended for breast cancer survivors , and past studies show benefits in quality of life and decreased inflammation . However , this has not been tested specifically in triple-negative breast cancer survivors . Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer . Therefore , the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat , physical function , and quality of life in survivors of this aggressive breast cancer . Secondarily , we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile . Methods Sixty-six survivors of triple-negative breast cancer with BMI > 25 were invited to participate . Twenty-eight enrolled and 23 completed the r and omized , controlled trial ( 13 intervention , 10 control ) . Moderate-intensity aerobic exercise ( 150 min per week , for 12 weeks ) and diet counseling were compared to usual care , education only . The primary outcome of interest was weight loss ( body mass , BMI , % fat ) , and secondary outcomes included physical function ( exercise capacity ) , quality of life ( Function After Cancer Therapy — Breast ( FACT-B ) ) , cytokines ( C-reactive protein ( CRP ) , TNF-α , IL-6 ) , and adipokine profile ( leptin , adiponectin , insulin ) . Results Participants in the program lost more body fat ( 2.4 % loss vs. 0.4 % gain , p < 0.05 ) than the control group . The intervention group also improved quality of life ( FACT-B total score + 14 pts ) and decreased sedentary time but did not improve peak exercise capacity . The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program . However , serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group ( p < 0.05 ) . Conclusions Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer . BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention . Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program Obesity is a poor prognostic factor and is negatively related to quality of life ( QOL ) in breast cancer survivors . Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors . Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % ( p < 0.0001 ) and 3.7 versus 1.3 % ( p < 0.0001 ) at 12 and 24 months , respectively . ENERGY also was design ed to answer the research question : Does weight loss significantly improve vitality and physical function ( key components of QOL ) ? 692 breast cancer survivors ( BMI : 25–45 kg/m2 ) at 4 US sites were r and omized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive ( control ) of two in-person counseling sessions . Weight , self-reported QOL , and symptoms were measured semi-annually for two years . Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months , but not in the intervention arm , −3.45 ( 95 % Confidence Interval [ CI ] −6.10 , −0.79 , p = 0.0109 ) and 0.10 ( 95 % CI 0.04 , 0.16 , p = 0.0021 ) , respectively . Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm −2.72 ( 95 % CI −5.45 , 0.01 , p = 0.0508 ) . These differences diminished over time ; however , depressive symptoms increased in the intervention versus control arms and became significant at 24 months , −1.64 ( 95 % CI −3.13 , −0.15 , p = 0.0308 ) . Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors . These longer term data suggest that diet and exercise interventions improve some aspects of QOL , but these benefits may diminish over time PURPOSE / OBJECTIVES To investigate the feasibility and preliminary effects of a simultaneous stage-matched exercise and diet ( SSED ) intervention in breast cancer survivors . DESIGN R and omized , controlled trial . SETTING Oncology outpatient treatment clinics at the National Cancer Center in South Korea . SAMPLE 45 women with breast cancer who completed their cancer therapy . METHODS Participants were assigned to the SSED intervention group ( n = 23 ) or a control group ( n = 22 ) . Participants in the SSED group received a 12-week individualized intervention promoting prescribed exercise and a balanced diet through stage-matched telephone counseling and a workbook . MAIN RESEARCH VARIABLES Program feasibility , behavioral outcomes ( stage of motivational readiness for exercise and diet , physical activity , and diet quality ) , and quality -of-life ( QOL ) outcomes ( functioning and global QOL , fatigue , anxiety , and depression ) . FINDINGS Participant evaluations of the SSED intervention indicated that it was feasible and acceptable . All women felt that the overall intervention contents were appropriate , and 95 % believed that the intervention helped to promote healthy behaviors . Objective data also supported the SSED intervention 's feasibility ( i.e. , 91 % completed the trial and 100 % of intervention calls were received ) . When compared to control , the SSED intervention group showed significantly greater improvement in motivational readiness for exercise and diet , emotional functioning , fatigue , and depression . CONCLUSIONS Preliminary results suggest that the SSED intervention delivered via telephone counseling and workbook is feasible and beneficial for positive behavioral and QOL outcomes . IMPLICATION S FOR NURSING Nurse-led lifestyle interventions may improve QOL for cancer survivors Energy restriction from a low-calorie diet and increased energy expenditure induced by physical activity ( PA ) could promote weight loss/maintenance and be important determinants of breast cancer ( BC ) prognosis . The aim of this study was to assess participation and adherence of overweight and obese BC survivors to a lifestyle intervention and to demonstrate the capacity of this intervention to induce weight loss and nutritional changes . This single-arm pre – post study , which involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi-weekly PA sessions of moderate-to-high intensity led by PA monitors , was offered to overweight and obese BC survivors shortly after treatment . Before and after the intervention , anthropometry , dietary information , quality of life ( QoL ) and cardiorespiratory fitness ( CRF ) were collected . A total of 112 BC survivors were invited to participate : 42 of them started the intervention and 37 completed it . Participants attended more than 90 % of the sessions offered and showed a significant weight loss of 5.6 ± 2.0 kg , as well as significant decreases in body mass index , fat mass and waist circumference . Significant decreases in total energy ( −25 % ) , fat ( −35 % ) , saturated fat ( −37 % ) and carbohydrate ( −21 % ) intakes were observed while QoL and CRF showed significant increases . This feasibility study demonstrated the success of a short-term diet and PA intervention to induce weight loss and promote healthful changes in BC survivors . Assessing the long-term effects of these changes , and in particular their possible impact of BC prognosis , and design ing interventions reaching a wider number of BC survivors are still issues to be addressed Background The quality of life for breast cancer survivors has become increasingly important because of their high survival rate and prolonged life expectancy . The purpose of this study was to examine the association of physical activity following diagnosis and health-related quality of life ( HRQOL ) in breast cancer survivors . Methods We conducted a cross-sectional study of breast cancer survivors . A total of 231 women aged 21–78 years who had been diagnosed with stages I to III breast cancer and had breast cancer surgery at least 6 months prior were recruited from three hospitals between September 2012 and April 2015 and were included in this study . We asked participants about their HRQOL and engagement in physical activity using structured question naires . We examined the association between HRQOL levels and physical activity using a generalized linear model . Results Breast cancer survivors in the high physical activity group ( 3rd tertile ) were more likely to have lower scores for fatigue ( p for trend = 0.001 ) and pain ( p for trend = 0.02 ) and higher scores for sexual function ( p for trend = 0.007 ) than those in the low physical activity group ( 1st tertile ) . When we stratified participants by stage , we found increasing scores for physical functioning ( p for trend = 0.01 ) and decreasing scores for fatigue ( p for trend = 0.02 ) with increasing levels of physical activity in breast cancer survivors with stage I breast cancer . In survivors with stages II and III , we found statistically significant associations with fatigue ( p for trend = 0.02 ) and sexual functioning ( p for trend = 0.001 ) . Conclusions In conclusion , engagement in physical activity was related to better health-related quality of life among breast cancer survivors . Our findings may warrant further prospect i ve and intervention studies to support the benefit of physical activity in improving the quality of life and survival of Korean breast cancer survivors OBJECTIVE To assess the effectiveness of an intervention aim ed to increase adherence to a Mediterranean diet . DESIGN A 12-month assessment of a r and omized primary prevention trial . SUBJECTS/ SETTING S One thous and five hundred fifty-one asymptomatic persons aged 55 to 80 years , with diabetes or > or =3 cardiovascular risk factors . INTERVENTION Participants were r and omly assigned to a control group or two Mediterranean diet groups . Those allocated to the two Mediterranean diet groups received individual motivational interviews every 3 months to negotiate nutrition goals , and group educational sessions on a quarterly basis . One Mediterranean diet group received free virgin olive oil ( 1 L/week ) , the other received free mixed nuts ( 30 g/day ) . Participants in the control group received verbal instructions and a leaflet recommending the National Cholesterol Education Program Adult Treatment Panel III dietary guidelines . MAIN OUTCOME MEASURES Changes in food and nutrient intake after 12 months . STATISTICAL ANALYSES Paired t tests ( for within-group changes ) and analysis of variance ( for between-group changes ) were conducted . RESULTS Participants allocated to both Mediterranean diets increased their intake of virgin olive oil , nuts , vegetables , legumes , and fruits ( P<0.05 for all within- and between-group differences ) . Participants in all three groups decreased their intake of meat and pastries , cakes , and sweets ( P<0.05 for all ) . Fiber , monounsaturated fatty acid , and polyunsaturated fatty acid intake increased in the Mediterranean diet groups ( P<0.005 for all ) . Favorable , although nonsignificant , changes in intake of other nutrients occurred only in the Mediterranean diet groups . CONCLUSIONS A 12-month behavioral intervention promoting the Mediterranean diet can favorably modify an individual 's overall food pattern . The individual motivational interventions together with the group sessions and the free provision of high-fat and palatable key foods customary to the Mediterranean diet were effective in improving the dietary habits of participants in this trial BACKGROUND Diet , smoking and physical activity are important modifiable lifestyle factors that can influence body weight and fat accumulation . We assessed the relationship between lifestyle and obesity risk in a baseline analysis of the PREDIMED study , a r and omized dietary primary prevention trial conducted in Spain . METHODS 7000 subjects at high cardiovascular risk were assessed cross-sectionally . A healthy lifestyle pattern ( HLP ) was determined using a score including : adherence to the Mediterranean diet , moderate alcohol consumption , expending ≥200 kcal/day in leisure-time physical activity , and non-smoking . RESULTS Inverse linear trends were observed between the HLP-score and body-mass-index ( BMI ) or waist circumference ( p<0.001 ) . The BMI and waist circumference of participants with a HLP-score=4 were , respectively , 1.3 kg/m(2 ) ( 95 % CI : 0.9 to 1.7 ) and 4.3 cm ( 3.1 to 5.4 ) lower than those of subjects with an HLP≤1 . The odds ratios of general obesity and abdominal obesity for an HLP score of 4 compared to an HPL score≤1 were 0.50 ( 0.42 to 0.60 ) and 0.51 ( 0.41 to 0.62 ) , respectively . CONCLUSION A combination of four healthy lifestyle behaviors was associated with a lower prevalence of general obesity and abdominal obesity in Mediterranean elderly subjects at high cardiovascular risk CONTEXT Five-year survival rates for early stage colorectal , breast , and prostate cancer currently exceed 90 % and are increasing . Cancer survivors are at greater risk for second malignancies , other comorbidities , and accelerated functional decline . Lifestyle interventions may provide benefit , but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status . OBJECTIVE To determine whether a telephone counseling and mailed print material -based diet and exercise intervention is effective in reorienting functional decline in older , overweight cancer survivors . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 641 overweight ( body mass index > or = 25 and < 40 ) , long-term ( > or = 5 years ) survivors ( aged 65 - 91 years ) of colorectal , breast , and prostate cancer , who were r and omly assigned to an intervention group ( n = 319 ) or delayed intervention ( control ) group ( n = 322 ) in Canada , the United Kingdom , and 21 US states . Individuals were recruited for the Reach out to Enhance Wellness ( RENEW ) trial from July 1 , 2005 , through May 17 , 2007 . INTERVENTION A 12-month , home-based tailored program of telephone counseling and mailed material s promoting exercise , improved diet quality , and modest weight loss . The control group was wait-listed for 12 months . MAIN OUTCOME MEASURES Change in self-reported physical function on the Short-Form 36 physical function subscale ( score range , 0 - 100 ; a high score indicates better functioning ) from baseline to 12 months was the primary end point . Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index ( score range , 0 - 100 ) , physical activity , body mass index , and overall health-related quality of life . RESULTS The mean baseline Short-Form 36 physical function score was 75.7 . At the 12-month follow-up , the mean function scores declined less rapidly in the intervention group ( -2.15 ; 95 % confidence interval [ CI ] , -0.36 to -3.93 ) compared with the control group ( -4.84 ; 95 % CI , -3.04 to -6.63 ) ( P = .03 ) . The mean baseline basic lower extremity function score was 78.2 . The mean changes in basic lower extremity function were 0.34 ( 95 % CI , -0.84 to 1.52 ) in the intervention group compared with -1.89 ( 95 % CI , -0.70 to -3.09 ) in the control group ( P = .005 ) . Physical activity , dietary behaviors , and overall quality of life increased significantly in the intervention group compared with the control group , and weight loss also was greater ( 2.06 kg [ 95 % CI , 1.69 to 2.43 kg ] vs 0.92 kg [ 95 % CI , 0.51 to 1.33 kg ] , respectively ; P < .001 ) . CONCLUSION Among older , long-term survivors of colorectal , breast , and prostate cancer , a diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00303875 Background : The advantages of adapted physical activity and nutritional education ( APANE ) on breast cancer prognosis and quality of life ( QoL ) are well known , but long-term results are lacking . Methods : A r and omised controlled trial testing a 2-week intervention in hydrothermal centres including APANE enrolled 251 patients post-chemotherapy . QoL and weight control were significantly improved at 12 months . A 5-year follow-up was performed to evaluate the persistence of improvements . Results : QoL increase ( SF36 ) was persistent : effect-size at 2 , 3 , 4 and 5 years equalled respectively 0.27 ( −0.01 ; 0.56 ) , 0.28 ( −0.02 ; 0.58 ) , 0.41 ( 0.02 ; 0.81 ) and 0.45 ( 0.11 ; 0.80 ) . Weight control observed after intervention lasted 2 years : 2.7 % decrease at 1 year ( P=0.0085 ) , 2.5 % at 2 years ( P=0.025 ) ; and respectively for waist −2.4 % ( −3.6 ; −1.1 ) ( P=0.000014 ) and −1.3 % ( −2.5 ; −0.1 ) ( P=0.0072 ) . Conclusions : A 2-week intervention in hydrothermal centres performed shortly after chemotherapy can durably improve breast cancer patients ’ QoL and reduce weight |
2,384 | 22,481,979 | Based on the current analysis a clear trend towards a potential role for HER2 as a negative prognostics factor in gastric cancer was shown , suggesting that HER2 overexpression and /or amplification is a molecular abnormality that might be linked to the development of gastric cancer | Through the recent conduct of the ToGA trial , HER2 has shown to be predictive for the treatment with trastuzumab in advanced gastric and gastro-oesophageal cancer .
When it comes to the prognostic properties the situation is different .
Despite the fact that it is more than 20 years ago since the first studies demonstrating an association between a positive HER2 status and poor prognosis were published the issue is still controversial .
In this current systematic review a large number of studies on HER2 and gastric cancer have been review ed . | 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 Resected specimens of 288 primary stomach cancers ( 175 early cases and 113 advanced cases ) and recurrent tumors or biopsy specimens of 21 recurrent or inoperable metastatic stomach cancers were examined immunohistochemically for expression of c-erbB-2 oncogene product . c-erbB-2 protein-positive staining was detected in 6.9 , 15.9 and 28.6 % of early , advanced and recurrent or inoperable metastatic stomach cancers , respectively , the difference being significant ( p < 0.005 ) . Four patients with advanced cancer showed positive staining in metastatic lymph nodes but not in the primary tumors . The results of tissue immunostaining were compared with c-erbB-2 protein levels in sera of the patients measured by an enzyme-linked immunosorbent assay . The levels of this oncogene product were consistently low in the sera of most of the patients with primary stomach cancers , regardless of whether or not c-erbB-2 protein was expressed in the tumor . However , in the recurrent or inoperable metastatic stomach cancers , 5 of 6 patients with c-erbB-2 protein-positive tumors showed elevated levels of c-erbB-2 protein in the serum . After following up c-erbB-2 protein levels in the sera of 3 patients during the period of chemotherapy against recurrent or inoperable metastatic disease , we found that the levels increased only in the late stage . These results suggest that , in stomach cancer , c-erbB-2 protein is likely to be excreted into the serum at a relatively late stage , reflecting systemic spread of the disease PURPOSE The c-erbB-2 gene ( encoding the protein p185 ) is overexpressed in diverse human cancers and has been implicated to be of prognostic value in gastric cancer . Recent studies suggest a role of p185 in tumor progression by specifically promoting the invasive capacity of tumor cells . Therefore , the present study was conducted with the following three objectives : ( 1 ) to support the prognostic value of c-erbB-2 in gastric cancer in a large prospect i ve series using a monoclonal antibody and a highly sensitive immunohistochemical method ; ( 2 ) to determine the association of c-erbB-2 expression with the expression of invasion-related genes ; and ( 3 ) to perform the first overall multivariate analysis including c-erbB-2 and the invasion-related tumor-associated protease systems . PATIENTS AND METHODS In a consecutive prospect i ve series of 203 gastric cancer patients ( median follow-up , 42 months ) , expression of c-erbB-2 and a panel of tumor-associated proteases and inhibitors by tumor cells were evaluated semiquantitatively ( score 0 to 3 ) and analyzed for correlation ( chi(2 ) test , Bonferroni-corrected ) . Kaplan-Meier survival analysis and multivariate Cox analysis were performed to determine the relative prognostic impact of c-erbB-2 and the invasion-related parameters . RESULTS Kaplan-Meier analysis ( log-rank statistics ) revealed a significant association of increasing expression of c-erbB-2 with shorter disease-free ( P = . 0023 ) and overall survival ( P = .0160 ) . High amounts of p185 were significantly associated with a high expression of urokinase-type plasminogen activator ( uPA ) ( P < .010 ) , uPA-receptor ( P = .030 ) , type-1 plasminogen activator inhibitor ( PAI ) ( P < .010 ) , type-2 PAI ( P = .021 ) , cathepsin D ( P = .036 ) , matrix metalloproteinase-2 ( P = . 024 ) , alpha-1-antichymotrypsin ( P = .025 ) , and alpha-2-macroglobulin ( P = .017 ) . Multivariate analysis considering these proteases/protease inhibitors , in addition to alpha-1-antitrypsin , tissue plasminogen activator , plasminogen , alpha-2-antiplasmin , and antithrombin III , and established prognostic parameters revealed that , in addition to surgical curability , pT stage , pN stage , and PAI-1 , c-erbB-2 is an independent prognostic factor for overall survival of curatively resected patients ( n = 139 ; P = .049 ; relative risk , 1.54 ; 95 % confidence interval , 1.08 to 1.67 ) and all patients ( P = .028 ; relative risk 1.33 ; 95 % CI , 1.28 to 1.38 ) . CONCLUSION c-erbB-2 is confirmed as a new independent , functional prognostic parameter for overall survival in gastric cancer , even when a panel of invasion-related factors , including the strong prognostic parameter PAI-1 , are considered . The significant correlation of p185 with several tumor-associated proteases supports the hypothesis that c-erbB-2 is a promoter of invasion and metastasis . This strongly suggests that c-erbB-2 may be a promising target for anti-invasive therapy in gastric cancer Amplification of the HER2 gene and over-expression of the HER2 protein in gastric cancer have been shown in a large number of studies . HER2 positivity can be detected in approximately 20 % of patients , which is a characteristic associated with poor prognosis . Pre clinical in vitro and in vivo studies have demonstrated that both trastuzumab and lapatinib are effective in different gastric cancer models and have thus lead to the initiation of clinical studies . In the first phase III study , the ToGA trial , HER2-positive patients with advanced gastroesophageal and gastric adenocarcinoma were r and omized to receive 5-fluorouracil/capecitabine and cisplatin either alone or in combination with trastuzumab . A statically significant gain in overall survival was seen in the patients who received the combined treatment of trastuzumab and chemotherapy . It is expected that the encouraging results from the ToGA trial will have an immediate impact on the management of patients and that routine HER2 testing of patients with advanced gastric cancer will be initiated within a relatively short period of time Using a prospect ively acquired data base of 290 patients with advanced gastric adenocarcinoma , the prognostic significance of serum levels of carcinoembryonic antigen ( CEA ) ( 237 patients ) , alphafeto protein ( AFP ) ( 164 patients ) , beta-human chorionic gonadotrophin ( beta HCG ) ( 165 patients ) , CA19 - 9 ( 64 patients ) and CA125 ( 104 patients ) and tissue staining for C-erb B-2 ( 160 patients ) and beta HCG ( 160 patients ) was investigated . Serum was taken prior to 5-fluorouracil (5FU)-based chemotherapy and immunohistochemistry was performed on diagnostic specimens . In the univariate analysis , tumour markers of poor prognosis were CEA > or = 5 micrograms/l ( P = 0.01 ; median survival ( MS ) 42 versus 35 weeks ) , serum beta HCG > or = 4 U/l ( P = 0.02 ; MS 42 versus 25 weeks ) , CA125 > or = 35 U/ml ( P = 0.03 ; MS 43 versus 31 weeks ) and CA125 > or = 350 U/ml ( P = 0.001 ; MS 42 versus 17 weeks ) . Other significant factors were poor performance status , the presence of metastases and poorly differentiated tumour histology . Tumours markers of poor prognosis in the multivariate analysis were serum beta HCG > or = 4 IU/l [ hazard ratio ( HR ) 1.7 ; 95 % confidence interval ( CI ) 2.8 - 1.1 ] and CA125 > or = 350 U/ml ( HR 2.2 ; CI 4.2 - 1.2 ) . There was a degree of subgroup variability in this model but , in general , other factors correlating with a poor survival were poor performance status , metastases and poorly differentiated tumour histology . This is the largest prognostic study of each tumour marker in advanced disease and demonstrates that serum beta HCG and CA125 in gastric cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology |
2,385 | 10,740,547 | Oral ketorolac 10 mg was consistently at least as effective as ketorolac 30 mg i.m . | null | null |
2,386 | 25,517,397 | Three small trials compared a mechanical device with no treatment and although they suggested that use of a mechanical device might be better than no treatment , the evidence for this was inconclusive .
While at three months there were more withdrawals from the device-only group , at 12 months differences between the groups were not sustained on any measure .
The place of mechanical devices in the management of urinary incontinence remains in question .
There was also insufficient evidence in favour of one device over another and little evidence to compare mechanical devices with other forms of treatment | BACKGROUND Incontinence can have a devastating effect on the lives of sufferers with significant economic implication s. Non-surgical treatments such as pelvic floor muscle training and the use of mechanical devices are usually the first line of management , particularly when a woman does not want surgery or when she is considered unfit for surgery .
Mechanical devices are inexpensive and do not compromise future surgical treatment .
OBJECTIVES To determine whether mechanical devices are useful in the management of adult female urinary incontinence . | An investigation was carried out on six hospitalized elderly male urinary incontinent patients for 21 days to test three urinary sheath systems by means of a quasi-experimental trial , incorporating crossover . Observations were made , and recorded , of detachment or leakage in systems and of skin condition round the shaft of the penis . Results suggest that two of the systems differ significantly in their performance and that performance of the urinary sheath was probably the limiting factor in overall performance . Incidence of skin problems , and other problems within systems , were minimal . It was also observed that patients differ significantly in their suitability for the application of sheath systems . This observation was made at two time intervals . A further line of investigation is suggested to test the effect of components , other than sheaths , on performance of systems A new system of urine collection to be used with indwelling catheters or condom drainage was developed and evaluated in the laboratory , and clinical ly . The aims included prevention of twisting of the tubes , non-leakage , comfortable body bags and ease of use of drainage taps . The new system was highly acceptable to patient and attendant alike A newly marketed vaginal sponge intended to support the urethra was tested during aerobic exercise in a group of 6 women suffering from stress urinary incontinence . The patients performed half an hour of aerobic exercises on 2 consecutive days , with and without the vaginal sponge . A pad was worn during exercise and weighed before and after . Without the vaginal sponge the patients had a mean loss of 7 g ( range 2–18 g ) during exercise . With the vaginal sponge in situ there was no leakage . The sponge can be recommended for use during sports in patients with mild to moderate incontinence Urethral devices are one conservative management option for stress and mixed urinary incontinence , but there is little published data about their use . The aims of this study were to assess the safety and efficacy of a new urethral device ( NEAT ) and compare it with the Reliance Insert . The ease of use of both devices was then evaluated . Twenty-four women with mixed or stress urinary incontinence , patients at our tertiary care urogynecology unit and who met the inclusion and exclusion criteria , were enrolled in the study . Study subjects were blinded and r and omly assigned to a device group . Device efficacy was assessed by pad weighing at 0 and 4 months . Success was defined as a 50 % or greater reduction in urine loss using the formula 100[(pad weight without device −pad weight with device)/pad weight with device ] . Safety was evaluated using urinalysis and urine cultures . Ease of use assessment scales were also completed . Eleven patients were r and omized to the Reliance Insert and 13 to the NEAT device . There were no significant differences between the two groups in age , height , weight , duration of incontinence , pad weight , leakage score , parity or quality of life score . Based on the pad weight success formula , there was no significant difference in device success between the two groups at 4 months . Women who were postmenopausal had a trend towards a higher level of success in reduction of their pad weight . Previous treatment , diagnosis and hormone replacement therapy all had no relationship to device success . Leakage score data showed that subjects had a significant decrease in urine leakage when using either device . There was no statistically significant difference in ease of use between the two devices . Adverse symptoms most commonly noted were awareness of the device ( 62.5 % ) , urgency ( 29.2 % ) , and urethral discomfort or pain ( 20.8 % ) . One urinary tract infection ( UTI ) was observed . The most common finding on urinalysis was trace hematuria ( 15.8 % ) . Our conclusions are that the NEAT device appears to be at least as effective and safe as the Reliance Insert . Both devices are effective at decreasing urine leakage in patients with stress or mixed urinary incontinence . The risk of UTI is low , but these devices may cause trace hematuria Objective The objective of this study was to determine if differences exist in pelvic symptom distress and impact on women r and omized to pessary versus behavioral therapy for treatment of stress urinary incontinence ( SUI ) . Methods Change in symptom and condition-specific health-related quality -of-life ( HRQOL ) measures were compared between pessary and behavioral groups 3 months after r and omization in the Ambulatory Treatments for Leakage Associated With Stress Incontinence trial . Four hundred forty-six women with symptoms of SUI were r and omized to continence pessary , behavioral therapy ( pelvic floor muscle training and continence strategies ) or combination therapy . Vali date d measures utilized included urinary , prolapse , and colorectal scales of the Pelvic Floor Distress Inventory ; urinary , prolapse , and colorectal scales of the Pelvic Floor Impact Question naire ; and Stress and Urge scales of the Question naire for Urinary Incontinence Diagnosis . Student t test and analysis of variance were used to compare scores within and between groups . Results Mean age of participants was 49.8 ( SD , 11.9 ) years ; 84 % were white , and 10 % were African American . One hundred forty-nine were r and omized to pessary , and 146 to behavioral therapy . Baseline symptoms and HRQOL scores were significantly reduced within treatment arms at 3 months after r and omization , but there was no statistically significant difference between groups . Conclusions There was no difference in pelvic floor symptom bother and HRQOL between the pessary and behavioral therapy arms in women undergoing conservative treatment for SUI . Individualized preference issues should be considered in the approach to the nonsurgical treatment of SUI A developed urethral plug was evaluated for the treatment of women with genuine urinary stress incontinence . The plug consists of an oval meatal plate , a soft stalk and one or two spheres along the stalk with fixed distances between the meatal plate and the spheres . Inside the stalk is a removable semi-rigid guide pin to ease insertion . Forty women were r and omly allocated to treatment with either the two-sphere or the one-sphere plug during period one ( two weeks ) . In period two ( two weeks ) the patients used the other plug . They then continued with what they judged to be the better plug in period three ( two months ) . Eighteen patients ( 45 % ) completed period three with the " preference " plug and 17 were subjectively and objective ly continent or improved . Fourteen of these women preferred the two-sphere device . The plugs were equally effective in patients with mild or severe incontinence . Six women developed urinary tract infections and two of these had a plug in the bladder . The urethral plug is an effective treatment in a group of women with stress incontinence . Removal by h and is advisable in order to avoid retention of plugs in the bladder Introduction and hypothesisManagement of stress urinary incontinence ( SUI ) with intravaginal devices is an alternative to surgical management , but data of a high level of evidence remain scarce . Our goal was to assess efficacy , tolerance , and acceptability of the 75NC007 intravaginal device for SUI management . Methods A phase III , multicenter r and omized controlled trial was conducted . After an initial washout period with no treatment , allowing baseline evaluation , women with SUI were r and omly assigned to a treatment or control group ( no treatment ) . The primary endpoint was the reduction of incontinence episode frequency ( IEF ) , according to bladder diaries , as compared to baseline . Secondary endpoints were variation of the Urinary Symptom Profile ( USP ) score , of 24-h pad test , and of CONTILIFE question naire scores as compared to baseline . Intent-to-treat and per- protocol analyses were conducted . Results Fifty-five patients were enrolled and analyzed ( 26 controls and 29 treated ) . The mean relative variations of IEF , SUI USP subscore , and overactive bladder ( OAB ) USP subscore were more significant in the treatment group than in the control group ( −31.7 ± 65.1 % vs −7.6 ± 24.5 % , p = 0.002 , −2.4 ± 2.6 vs 0.2 ± 2.2 , p = 0.004 , and −1.5 ± 2.8 vs 0.2 ± 1.8 , p = 0.016 , respectively ) . The dysuria USP subscore was slightly decreased in the treatment group . CONTILIFE scores were slightly improved in the treatment group . Pad test variations were not different between groups . No serious adverse event was noted throughout the entire study . Conclusions The 75NC007 intravaginal device is a safe and effective noninvasive treatment of SUI in women PURPOSE We evaluated the usefulness and safety of a bladder neck support prosthesis in patients with stress or mixed incontinence . MATERIAL S AND METHODS A total of 57 women with stress and 20 with mixed incontinence completed a 12-week prospect i ve clinical trial of a bladder neck support prosthesis . While indexes of incontinence episodes , leakage amounts and urgency along with a bothersome index were subjectively evaluated , a 60-minute pad test and urinary flow parameters were objective ly evaluated . Three patients scheduled to undergo surgery for stress incontinence voluntarily used the device , and provided urodynamic data and cystourethrograms . Two prongs at 1 end of the ring , a type of elastic vaginal pessary , elevate the bladder neck against the pubic bone and facilitate pressure transmission around the bladder neck , result ing in urinary continence . RESULTS Four subjective indexes significantly improved . There was no urinary flow obstruction . Urine loss decreased from 20.6 to 4.8 gm . per hour ( p < 0.001 ) on the 60-minute pad test . Of the patients 22 ( 29 % ) reported complete continence and 39 ( 51 % ) had decreased severity of incontinence by more than 50 % . Minor adverse effects occurred in 26 % of the patients . Taking subjective evaluation , changes in objective parameters and adverse effects into consideration , 62 patients ( 81 % ) had some or maximum benefit according to the global usefulness rating . CONCLUSIONS The bladder neck support prosthesis is safe , well tolerated and clinical ly effective for the treatment of stress or mixed incontinence OBJECTIVE : To identify factors that may predict success and satisfaction in women undergoing nonsurgical therapy for stress urinary incontinence . METHODS : Baseline demographic and clinical characteristics of women participating in a multicenter r and omized trial of pessary , behavioral , or combined therapy for stress urinary incontinence were evaluated for potential predictors of success and satisfaction . Success and satisfaction outcomes were assessed at 3 months and included the Patient Global Impression of Improvement , stress incontinence subscale of the Pelvic Floor Distress Inventory , and Patient Satisfaction Question naire . Logistic regression was performed to identify predictors , adjusting for treatment and other important clinical covariates . Adjusted odds ratios ( ORs ) , 95 % confidence intervals ( CIs ) , and associated P values are presented . RESULTS : Four hundred forty-six women were r and omized . College education or more and no previous urinary incontinence surgery predicted success based on the stress subscale of the Pelvic Floor Distress Inventory ( adjusted OR 1.61 , 95 % CI 1.01–2.55 , P=.04 and adjusted OR 3.15 , 95 % CI 1.04- 9.53 , P=.04 , respectively ) . Menopausal status predicted success using the Patient Global Impression of Improvement ( adjusted OR 2.52 postmenopausal compared with premenopausal , 95 % CI 1.29–4.95 ; adjusted OR 1.32 unsure menopausal status compared with premenopausal , 95 % CI 0.65–2.66 ; P=.03 across all three groups ) . Fewer than 14 incontinence episodes per week predicted satisfaction with the Patient Satisfaction Question naire ( adjusted OR 1.97 , 95 % CI 1.21–3.19 ; P=.01 ) . These predictors did not differ across the three treatment groups . CONCLUSION : Menopause , higher education , no previous urinary incontinence surgery , and lower incontinence frequency were found to be predictors of success and satisfaction with nonsurgical therapy for stress urinary incontinence . This information may help better-align provider and patient expectations with nonsurgical treatment outcomes . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00270998 . LEVEL OF EVIDENCE : OBJECTIVES The purpose of this study was to test the safety and effectiveness of a urethral insert for managing stress or mixed urinary incontinence . METHODS We performed a prospect i ve , multicenter study of 135 female patients who were treated for 4 months with the Reliance Urinary Control Insert . The effectiveness of the insert was measured objective ly at the time of first use and after 4 months ' use by st and ardized pad weight studies . Insert effectiveness was also measured by reports of symptom improvement during patient interviews and on patient diaries . Urine microscopy and culture were obtained monthly ; cystoscopy and urodynamics were conducted at study entry and at 4 months . RESULTS Significant improvement in involuntary urine loss was observed . Objective measurement of urine loss revealed that 80 % of the patients were completely dry , and 95 % of the patients achieved greater than an 80 % decrease in urine loss . In addition , patients ' perceptions of acceptability , incontinence symptom improvement , ease of learning , comfort , and time to habituation also showed improvements . Untoward events reported during the study included hematuria , bacteriuria , and bladder irritation . These events did not require significant medical intervention and did not result in any long-term clinical sequelae . CONCLUSIONS These preliminary results indicate that the Reliance Urinary Control Insert may be a safe , effective , and well-tolerated alternative to other available methods for the management of stress or mixed incontinence in women . Additional long-term follow-up will be required to substantiate this conclusion OBJECTIVE : To compare the effectiveness of a continence pessary to evidence -based behavioral therapy for stress incontinence and to assess whether combined pessary and behavioral therapy is superior to single-modality therapy . METHODS : This was a multisite , r and omized clinical trial ( Ambulatory Treatments for Leakage Associated with Stress Incontinence [ ATLAS ] ) that r and omly assigned 446 women with stress incontinence to pessary , behavioral therapy , or combined treatment . Primary outcome measures , at 3 months , were Patient Global Impression of Improvement and the stress incontinence subscale of the Pelvic Floor Distress Inventory . A priori , to be considered clinical ly superior , combination therapy had to be better than both single-modality therapies . Outcome measures were repeated at 6 and 12 months . Primary analyses used an intention-to-treat approach . RESULTS : At 3 months , scores from 40 % of the pessary group and 49 % of the behavioral group were “ much better ” or “ very much better ” on the Patient Global Impression of Improvement ( P=.10 ) . Compared with the pessary group , more women in the behavioral group reported having no bothersome incontinence symptoms ( 49 % compared with 33 % , P=.006 ) and treatment satisfaction ( 75 % compared with 63 % , P=.02 ) . Combination therapy was significantly better than pessary as shown on the Patient Global Impression of Improvement ( 53 % , P=.02 ) and Pelvic Floor Distress Inventory ( 44 % , P=.05 ) but not better than behavioral therapy ; it was therefore not superior to single-modality therapy . Group differences were not sustained to 12 months on any measure , and patient satisfaction remained above 50 % for all treatment groups . CONCLUSION : Behavioral therapy result ed in greater patient satisfaction and fewer bothersome incontinence symptoms than pessary at 3 months , but differences did not persist to 12 months . Combination therapy was not superior to single-modality therapy . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00270998 . LEVEL OF EVIDENCE : Objective To determine the proportion of unselected women with genuine stress incontinence in whom a bladder neck support prosthesis could be fitted successfully by three gynaecologists with no prior knowledge of the device , and to measure efficacy of the device Objective To evaluate the full range of self‐adhesive continence sheaths for men available in the UK and thus provide clinicians and consumers with a basis for product selection It is estimated that 30 % of nursing home residents may be faecally incontinent , with those figures rising to 60 % for patients in long-stay hospitals ( Royal College of Physicians , 1995 ) . Maintaining skin integrity for these patients can be complex . With little clinical information to support carers , choosing a skin care regime that maintains skin integrity for this high-risk group can be difficult . This study aims to compare two recognized skin care regimes , used in the cleansing of patients ' skin following an episode of incontinence , and their impact on patients ' skin integrity . A total of 93 patients were recruited to the trial from five care of the elderly or dependent service providers . The subjects were r and omly allocated to either group A ( soap and water ; n = 49 ) , or group B ( Clinisan ( Vernacare ) ; n = 44 ) . Initially , 33 patients in both groups started with healthy skin . However , the results of the final assessment identified only 17 subjects in group A remaining healthy , compared with 27 in group A prospect i ve , r and omized , single-blind study addressed the hypothesis that simple mechanical barriers are helpful in controlling urinary incontinence during exercise . Eighteen incontinent exercisers aged 33 - 73 participated in three 40-minute st and ardized aerobics sessions wearing either a Hodge pessary with support , a super tampon or no mechanical device . Urine loss was determined by a change in the weight of the pad worn while exercising . Statistical analysis of the log of urine loss revealed that women lost significantly less urine when exercising with either the pessary or the tampon than when exercising with no device . Thus , both devices studied are useful , nonsurgical alternatives for some women for the treatment of exercise incontinence Objective To compare two versions of the same type of disposable intravaginal device ( the Conveen Continence Guard , CCG , and the Contrelle Continence Tampon , CCT , Coloplast a/s , Humlebæk , Denmark ) for treating stress incontinence in women |
2,387 | 28,866,854 | Inverse bidirectional relationships were found between decreased HRQoL and increased OD severity .
Following intervention , changes were evident through improved HRQoL with decreased OD severity .
The findings of this paper highlight the importance of targeting HRQoL in patients with OD . | The negative impact of increased bolus modification on health-related quality of life ( HRQoL ) in persons with oropharyngeal dysphagia ( OD ) has been described in previous literature ; however , findings may have been influenced by the severity of OD and underlying etiology .
The current systematic review therefore aims to investigate the relationships between HRQoL and OD and to report on changes in HRQoL and OD following intervention . | Purpose This study aim ed to assess the effectiveness of functional electrical stimulation on the swallowing function of irradiated nasopharyngeal carcinoma patients with dysphagia . Material s and methods Twenty nasopharyngeal carcinoma subjects with dysphagia were divided into a functional electrical stimulation ( FES ) and a home rehabilitation program ( HRP ) group . Each subject completed a quality of life question naire on swallowing and a videofluoroscopic study at the commencement and the end of the procedures . The FES group received functional electrical stimulation of the supra-hyoid muscles over 15 sessions . The HRP group performed self-swallowing exercises at home . The evaluation parameters included the quality of life question naire scores , the penetration – aspiration scale ( PAS ) , the movement of the hyoid bone , and the amount of pyriform sinuses stasis . Results Most swallowing outcomes of the FES group improved after FES . The quality of life score ( p = 0.003 ) , the duration of the movement of thin barium through the hyoid ( p = 0.001 ) , the moving speed of paste barium through the hyoid ( p = 0.028 ) , and the pyriform sinus stasis area of the paste barium ( p = 0.026 ) reached significant difference in the FES group . Most swallowing outcomes did not improve in the HRP group . The degree of improvement in the movement speed of the hyoid bone in the thin barium ( p = 0.018 ) and the PAS of the paste barium ( p = 0.016 ) were statistically significantly greater in the FES group than in the HRP group . Conclusion FES will improve the swallowing function of NPC patients with dysphagia and bring about better quality of life OBJECTIVES Dysphagia is a common and debilitating side effect of chemoradiotherapy . Assessment is difficult ; swallowing is multifactorial and studies choose from a range of dysphagia assessment s. This study intended to investigate the relationship between swallowing assessment s of dysphagia in a cohort of patients and to evaluate whether clinical swallowing measures can predict patient reported swallowing outcomes . MATERIAL S AND METHODS One hundred and seventy-three head and neck cancer patients from two teaching hospitals were recruited prospect ively over 25 months . At three months follow-up patients were assessed using Rosenbeck 's Penetration-Aspiration Scale ( PAS ) , The 100 ml Water Swallow Test ( WST ) , The Performance Status Scale : Normalcy of Diet and the MD And erson Dysphagia Inventory ( MDADI ) . RESULTS The highest correlation was observed between the MDADI and Normalcy of Diet ( rho 0.68 ) and the lowest between the MDADI and the PAS ( rho 0.34 ) . Using multiple regression the PAS and WST accounted for 44 % of the variance in the MDADI scores ( R2 = 0.44 , F = 37.8 , p < 0.001 ) . On stepwise regression , the model only retained the Normalcy of Diet scores ( R2 = 0.42 , F=107.9 , p < 0.001 ) . Separating the PAS into subgroups , those with no penetration or aspiration on the PAS scored significantly higher on the MDADI ( p = < 0.001 ) . CONCLUSION Patient reported swallowing outcomes were strongly aligned with diet restrictions but poorly aligned with clinical assessment . The WST , however , was more correlated than the PAS score , representing a more functional assessment . Clinical dysphagia , associated with significant morbidity , and patient reported dysphagia related to quality of life are not interchangeable and must be measured separately OBJECTIVE To design a reliable and vali date d self-administered question naire whose purpose is to assess dysphagia 's effects on the quality of life ( QOL ) of patients with head and neck cancer . DESIGN Cross-sectional survey study . METHODS Focus groups were convened for question naire development and design . The M. D. And erson Dysphagia Inventory ( MDADI ) included global , emotional , functional , and physical subscales . One hundred consecutive adult patients with a neoplasm of the upper aerodigestive tract who underwent evaluation by our Speech Pathology team completed the MDADI and the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) . Speech pathologists completed the Performance Status Scale for each patient . Validity and reliability properties were calculated . Analysis of variance was used to assess how well the MDADI discriminated between groups of patients . RESULTS The internal consistency reliability of the MDADI was calculated using the Cronbach alpha coefficient . The Cronbach alpha coefficients of the MDADI subscales ranged from 0.85 to 0.93 . Test-retest reliability coefficients of the subscales ranged from 0.69 to 0.88 . Spearman correlation coefficients between the MDADI subscales and the SF-36 subscales demonstrated construct validity . Patients with primary tumors of the oral cavity and oropharynx had significantly greater swallowing disability with an adverse impact on their QOL compared with patients with primary tumors of the larynx and hypopharynx ( P<.001 ) . Patients with a malignant lesion also had significantly greater disability than patients with a benign lesion ( P<.001 ) . CONCLUSIONS The MDADI is the first vali date d and reliable self-administered question naire design ed specifically for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer . St and ardized question naires that measure patients ' QOL offer a means for demonstrating treatment impact and improving medical care . The development and validation of the MDADI and its use in prospect i ve clinical trials allow for better underst and ing of the impact of treatment of head and neck cancer on swallowing and of swallowing difficulty on patients ' QOL UNLABELLED Dysphagia can be a consequence of total laryngectomy even in the absence of symptoms and it could indeed directly or indirectly compromise quality of life . AIM To evaluate the characteristics of swallowing after total laryngectomy and pharyngolaryngectomy with pharyngeal T closure , correlating them with the Quality of Life in Swallowing Disorders question naire . METHODS A prospect i ve evaluation was performed in 28 patients ; fifteen undergoing total laryngectomy and thirteen undergoing total pharyngolaryngectomy . Swallowing was evaluated through videofluoroscopy regarding the preparatory , oral and pharyngeal phases of swallowing , and the quality of life related to swallowing question naire was employed to measure quality of life . RESULTS Anatomical and functional changes were observed under videofluoroscopic evaluation . Dysphagia was diagnosed in 18 patients ( 64.3 % ) , being mild in 66.6 % and moderate/severe in 33.3 % . The question naire indicated good quality of life in almost all scales . Complaints of dysphagia were associated to the burden ( p=0.036 ) and mental health scale ( p=0.031 ) . The question naire indicated impact on the mental health scale for patients with severe dysphagia ( p=0.012 ) . CONCLUSIONS High incidence of dysphagia was observed in some quality of life assessment s , especially of mild degree Aims : To evaluate the patient-to-patient model and swallowing problems in Chinese patients with supraglottic laryngeal cancer ( SLC ) , and to find a solution to help SLC patients with swallowing problems . Methods : Eighty-nine patients who had undergone operation for horizontal partial laryngectomy were chosen and divided r and omly into two groups . The European Organization for Research and Treatment of Cancer ( EORTC ) , Swallow Quality -of-Life ( SWAL-QOL ) and Visual Analogue Scale ( VAS ) question naires were used to measure the quality of life and swallowing situation of those patients . Results : At 0.5 and 1 months after eating , the scores of the EORTC QLQ-C30 and SWAL-QOL of the participant group were significantly higher than those of the nonparticipant group ( p < 0.05 ) . One week after eating , the VAS score for swallowing improved significantly from 4.9 to 7.9 in the participant group . However , in the nonparticipant group , the VAS score showed no obvious change ( from 4.5 to 4.1 ) . Conclusions : We concluded that the patient-to-patient model may be utilized in clinical cases to solve swallowing problems of SLC patients , and infered that swallowing problems mainly appeared in 60 to 70-year-olds , and 1 week after eating was a critical time point of communication Recent and specific data on the prevalence and /or incidence of oropharyngeal dysphagia in the general population are scarce . This study focuses on obtaining this data by means of a literature review and telephone survey . A literature review was performed to obtain data on the prevalence of dysphagia in the general population . Secondly , a quasi-r and om telephone survey using the functional health status question naire EAT-10 was conducted with the aim of establishing prevalence data on oropharyngeal dysphagia in the Netherl and s. The literature review revealed six articles which met the inclusion criteria . The prevalence data on oropharyngeal dysphagia in the general population varied between 2.3 and 16 % . For the telephone survey , a total of 6,700 individuals were contacted by telephone , of which , 2,600 ( 39 % ) participated in the study . Of the 2,600 participants , as many as 315 ( 12.1 % ) were identified as having swallowing abnormalities and showed increased risk of oropharyngeal dysphagia with age . Prevalence data on oropharyngeal dysphagia in the Dutch general population were as high as 12.1 % . This data are in line with the retrieved prevalence data from the literature This study compares the effects of traditional logopedic dysphagia treatment with those of neuromuscular electrical stimulation ( NMES ) as adjunct to therapy on the quality of life in patients with Parkinson ’s disease and oropharyngeal dysphagia . Eighty-eight patients were r and omized over three treatment groups . Traditional logopedic dysphagia treatment and traditional logopedic dysphagia treatment combined with NMES at sensor or motor level stimulation were compared . At three times ( pretreatment , post-treatment , and 3 months following treatment ) , two quality -of-life question naires ( SWAL-QOL and MD And erson Dysphagia Inventory ) and a single-item Dysphagia Severity Scale were scored . The Functional Oral Intake Scale was used to assess the dietary intake . After therapy , all groups showed significant improvement on the Dysphagia Severity Scale and restricted positive effects on quality of life . Minimal group differences were found . These effects remained unchanged 3 months following treatment . No significant correlations were found between dietary intake and quality of life . Logopedic dysphagia treatment results in a restricted increased quality of life in patients with Parkinson ’s disease . In this r and omized controlled trial , all groups showed significant therapy effects on the Dysphagia Severity Scale and restricted improvements on the SWAL-QOL and the MDADI . However , only slight nonsignificant differences between groups were found The aim of this work was to translate the 44-item SWAL-QoL into Dutch ( SWAL-QoL-NL ) and compare the validity of this question naire against Euroqol in a Dutch population with dysphagia . SWAL-QoL was translated according to international guidelines . SWAL-QoL-NL and Euroqol were completed by 152 patients in seven diagnosis groups . Internal consistency and correlations were calculated . Scores for nine subscales ( General burden , Food selection , Eating duration , Fear of eating , Sleep , Fatigue , Mental health , Social functioning and a symptom score ) ranged between 0.80 and 0.92 ( Cronbach ’s α ) . Two subscales ( Eating desire and Communication scored 0.67 and 0.60 , respectively , and were removed from the question naire . The 14-item battery on clinical symptoms showed an internal consistency of 0.80 , allowing the use of a sum score on group level in clinical research . Correlation of SWAL-QoL-NL subscales with the Euroqol was negligible to low ( Pearson ’s correlations range = 0.09–0.36 ) . The 39-item SWAL-QoL-NL proved to be a reliable tool to examine the impact of dysphagia on quality of life in a Dutch population . Internal consistency allows the use of nine subscales of SWAL-QoL-NL for comparisons on a group level ( 0.80 < α < 0.92 ) only . Also a Symptom score can be derived from the raw data This prospect i ve , cross-sectional study evaluated the impact of dysphagia on quality of life in healthy ageing and in subjects with Parkinson ’s disease ( PD ) using the Swallowing Quality of Life ( SWAL-QOL ) question naire . Sixteen healthy young adults ( 8 males , mean age = 25.1 years ) and 16 healthy elders ( 8 males , mean age = 72.8 years ) were recruited . Thirty-two subjects with idiopathic PD ( mean age = 68.5 years ) were recruited from a movement disorders clinic . The severity of PD was staged using the Hoehn and Yahr scale . Results revealed that elders experienced symptoms of dysphagia more frequently than young adults but the overall SWAL-QOL scores were not significantly different . Subjects with PD who experienced dysphagia reported greatly reduced QOL , and significant differences were found in all but one subsection of the SWAL-QOL . Disease progression detrimentally impacts QOL , with subjects in later-stage PD experiencing further reduction in the desire to eat , difficulty with food selection , and prolonged eating duration . These features , which increase with disease severity , are likely to impact negatively upon nutritional status , which is already under threat from PD-related dysphagia OBJECTIVE To prospect ively evaluate the impact of parathyroidectomy on swallowing-related quality of life using the Swallowing Quality Of Life ( SWAL-QOL ) vali date d outcomes assessment tool . BACKGROUND Many patients with primary hyperparathyroidism report nonspecific symptoms , such as fatigue , irritability , cognitive impairment , sleep disturbances , and dysphagia . To date , there have been no prospect i ve studies evaluating swallowing function before and after parathyroid surgery . METHODS Patients undergoing parathyroidectomy from September 2007 to January 2009 completed the SWAL-QOL question naire before and one year after surgery . Data were collected on demographic and clinicopathologic variables . Comparisons were made to determine the effect of surgery on patients ' perceptions of swallowing function . RESULTS Of 151 eligible patients , 102 ( 68 % ) completed the study . The mean patient age was 60 years , and 79 % were female . A total of 73 patients ( 67 % ) had minimally invasive parathyroidectomies , whereas the remainder had bilateral explorations . In all , 83 patients ( 81 % ) had a parathyroid adenoma , 16 patients ( 16 % ) had hyperplasia , and 3 patients ( 3 % ) had a double adenoma on final pathologic interpretation . Mean preoperative SWAL-QOL scores were < 90 for 4 of the 11 domains , indicating the perception of oropharyngeal dysphagia and diminished quality of life . Following parathyroidectomy , significant improvements were demonstrated in eight SWAL-QOL domains . CONCLUSIONS Many patients with parathyroid disease have the perception of abnormal swallowing function . In these patients with symptoms of dysphagia , parathyroid surgery leads to significant improvements in many aspects of swallowing-related quality of life measured by the SWAL-QOL instrument . This study represents the first use of a condition-specific instrument to assess swallowing-related quality of life for patients with parathyroid disease before and after parathyroid surgery OBJECTIVES /HYPOTHESIS Evaluation of long-term patient-perceived functional outcomes and quality of life ( QOL ) related to communication and eating with an emphasis on voice , speech production , and swallowing after cerebello-pontine angle ( CPA ) surgery . STUDY DESIGN Prospect i ve cross-sectional study . METHODS The MD And erson Dysphagia Inventory ( MDADI ) , Voice H and icap Index ( VHI ) , and Facial Clinimetric Evaluation ( FaCE ) surveys were distributed to patients who underwent CPA surgery between January 2008 and December 2010 . Immediate postoperative cranial nerve function extracted from medical records was compared to long-term patient-perceived function and associated QOL . RESULTS There was a 61 % response rate with a mean postoperative period of 31.6 months ( range 15 - 49 ) . The presence of facial palsy in the postoperative period and the corresponding House-Brackmann ( H-B ) score were the strongest predictors of patient-perceived long-term function and QOL in all three domains ( P < .005 ) . Postoperative vagal palsy by comparison was not associated with long-term disturbance of voice or speech function . Postoperative dysphagia had a particularly large association with perceived long-term facial function and related QOL ( P < .0005 ) , with a smaller but significant impact on perceived swallow outcome ( P < .05 ) . After adjusting for other variables , the postoperative H-B score remained a significant predictor of perceived long-term facial and voice function and related QOL . CONCLUSIONS Patients with severe facial dysfunction following surgery to the CPA are at increased risk for long-term self-reported difficulties with communication and eating , even with improvement of vagal function . Speech and swallow therapy should therefore be provided to these patients whether or not they also have pharyngeal dysphagia or voice disturbance . LEVEL OF EVIDENCE 2b Background : Patients with cancers of the upper aerodigestive tract ( head and neck cancer ( HNC ) ) tend to aspirate , either due to disease or treatment . The association of aspiration ( documented on video fluorography ( VFG ) ) with quality of life ( QOL ) and unexpected mortality was studied prospect ively in patients treated with simultaneous integrated boost technique of intensity-modulated radiotherapy ( SIB-IMRT ) . Material s and Methods : Moderately advanced ( stage III/IV ) HNC were treated by SIB-IMRT delivering 66 Gy/30 fr , 60 Gy/30 fr , and 54 Gy/30 fr to high , intermediate , and low risk volumes , respectively . They underwent serial VFG and QOL assessment s ( Quality of Life Question naire-Core 30 ( QLQ-C30 ) and head and neck-35 ( HN35 ) European Organisation for Research and Treatment of Cancer ( EORTC ) tools ) at 0 , 3 , and 6 months . Pharyngeal musculature ( PM ) was additionally delineated on planning computed tomography ( CT ) scans as potential organs at risk ( OARs ) . Results : Between November 2009 and May 2011 , 20 HNC were treated as per protocol . All patients were fit ( Karnofsky performance status ( KPS ) ≥ 80 ) . Based on VFG findings , seven patients ( 4/9 oropharynx and 3/11 laryngopharynx ) were grouped as aspirators ( A ) and remaining 13 as non-aspirators ( NA ) . The QOL study showed that pretreatment coughing and swallowing difficulties were greater in group A versus NA and remained persistently higher . In group A , deaths attributable to aspiration were seen in 3/7 patients , while none occurred in the NA group ( Fisher 's exact P = 0.03 ) . The mean PM dose was 60 Gy in both the groups and mean V60 was similar at 69 and 67 % in A and NA groups , respectively . Conclusions : VFG helps identify patients who aspirate and are at risk of premature death due to its complications , alerting caregivers to direct attention appropriately OBJECTIVE To evaluate and compare the effects of neuromuscular electrical stimulation ( NMES ) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infa rct ion . DESIGN Prospect i ve r and omized controlled study . SETTING Department of physical medicine and rehabilitation . PARTICIPANTS Patients with dysphagia with medullary infa rct ion ( N=82 ) . INTERVENTIONS Participants were r and omized over 3 intervention groups : traditional swallowing therapy , sensory approach combined with traditional swallowing therapy , and motor approach combined with traditional swallowing therapy . Electrical stimulation sessions were for 20 minutes , twice a day , for 5d/wk , over a 4-week period . MAIN OUTCOME MEASURES Swallowing function was evaluated by the water swallow test and St and ardized Swallowing Assessment , oral intake was evaluated by the Functional Oral Intake Scale , quality of life was evaluated by the Swallowing-Related Quality of Life ( SWAL-QOL ) Scale , and cognition was evaluated by the Mini-Mental State Examination ( MMSE ) . RESULTS There were no statistically significant differences between the groups in age , sex , duration , MMSE score , or severity of the swallowing disorder ( P>.05 ) . All groups showed improved swallowing function ( P≤.01 ) ; the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups , and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group ( P<.05 ) . SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group , and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences ( P=.04 ) . CONCLUSIONS NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infa rct ion . A sensory approach appears to be better than a motor approach |
2,388 | 28,267,032 | Conclusion There is limited evidence to support the use of any single hemostatic method to prevent RAO rates after percutaneous coronary procedures .
Although used extensively , there is evidence of no effect of the pneumatic compression method using the TR b and on the incidence of RAO at discharge or follow-up , the time taken to obtain hemostasis and the incidence of hematoma .
The MAP-guided compression method and the Biopolymer dressing ( Chitosen ) were superior to the TR b and compression method , and patent hemostasis was superior to hemob and in the prevention of RAO . | Background Transradial access to percutaneous coronary procedures is becoming the preferred access route , and it is being increasingly used for emergent and elective procedures .
However , radial artery occlusion ( RAO ) continues to remain an adverse occurrence following sheath removal or in the first 24 hours following sheath removal due to the smaller diameter of the artery .
Objectives The overall objective of this study was to synthesize the best available research evidence related to the effects of methods used to achieve hemostasis on RAO rates after percutaneous coronary procedures .
Types of intervention(s ) The interventions of interest were the use of various hemostatic methods compared to traditional interventions to prevent RAO .
Search strategy The search aim ed to find published and unpublished trials through electronic data bases , reference lists and key reports . | Background and Objective : Transradial access is an attractive approach for angiography or percutaneous coronary intervention . Different devices have been used to apply pressure locally at the site of arterial entry for achieving hemostasis . The aim of this study was to evaluate the effect of 2 different hemostatic devices on radial artery outcomes after transradial coronary intervention . Subjects and Methods : This study included 600 patients who had undergone transradial coronary intervention who were r and omized into 2 groups after the procedure : 300 were treated with a radial compression device ( TR B and , Terumo Medical , Tokyo , Japan ) ( CD group ) and the other 300 patients were treated using a chitosan-based pad ( Anscare , Daxon , Taoyuan , Taiwan ) ( CS group ) . Compression time , major and minor access site bleeding complications , and incidence of radial artery occlusion were recorded . Results : There were no statistical differences in the baseline clinical characteristics of the patients between the 2 groups . Compression time in the CS group was significantly shorter than that in the CD group ( P < .001 ) . Although no major access site bleeding complications were observed in either group , 6 patients in each group experienced minor access site bleeding complications . At the same time , 61 patients in the CD group and 21 patients in the CS group experienced errhysis ( 20 % vs 7 % , respectively ; P < .001 ) . Early radial artery occlusion ( 24 hours ) occurred in 11.7 % of the patients in the CD group and 5.4 % of the patients in the CS group ( P < .05 ) . Chronic radial artery occlusion ( 30 days ) occurred in 10 % of the patients in the CD group and 5 % of the patients in the CS group ( P < .05 ) . Conclusion : The application of the chitosan-based pad showed better hemostatic efficacy and a lower incidence of radial artery occlusion after transradial coronary intervention compared with the compression device Here , we evaluate the efficacy of the Clo-Sur PAD nonwoven hydrophilic wound dressing ( HWD ) on hemostasis in an arterial-access site after transradial percutaneous coronary angiography compared with the RadiStop compression device ( CD ) . Eighty patients who had undergone transradial coronary angiography with or without intravascular ultrasound were r and omly assigned to the HWD or CD group . The time required to achieve hemostasis was measured , and the incidence of vascular complications was assessed . No significant differences in clinical and procedural characteristics were observed between the HWD group ( n = 40 ) and the CD group ( n = 40 ) . A significant reduction in the time required to achieve hemostasis ( 58.7 + /- 32.6 minutes versus 131.3 + /- 59.1 minutes ; p < 0.001 ) was associated with the use of HWD . The incidence of vascular complications was similar in both groups ( 5 % for HWD versus 2.5 % for CD ; p = 0.500 ) . No major complications , such as large hematoma or acute radial occlusion , occurred in the HWD group . In conclusion , HWD represents a safe alternative to the compression method . Hemostasis can be achieved more quickly using HWD , with no increase in access site complications , as compared to CD Objective : The objective of this study was to evaluate the efficacy of hemostasis with patency in avoiding radial artery occlusion after transradial catheterization . Background : Radial artery occlusion is an infrequent but discouraging complication of transradial access . It is related to factors such as sheath to artery ratio and is less common in patients receiving heparin . Despite being clinical ly silent in most cases , it limits future transradial access . Patients and Methods : Four hundred thirty‐six consecutive patients undergoing transradial catheterization were prospect ively enrolled in the study . Two hundred nineteen patients were r and omized to group I , and underwent conventional pressure application for hemostasis . Two hundred seventeen patients were r and omized to group II and underwent pressure application confirming radial artery patency using Barbeau 's test . Radial artery patency was studied at 24 hr and 30 days using Barbeau 's test . Results : Thirty‐eight patients had evidence of radial artery occlusion at 24 hr . Twenty patients had persistent evidence of radial artery occlusion at 1 month . Group II , with documented patency during hemostatic compression , had a statistically and clinical ly lower incidence of radial artery occlusion ( 59 % decrease at 24 hr and 75 % decrease at 30 days , P < 0.05 ) , compared with patients in group I. Low body weight patients were at significantly higher risk of radial artery occlusion . No procedural variables were found to be associated with radial artery occlusion . Conclusion : Patent hemostasis is highly effective in reducing radial artery occlusion after radial access and guided compression should be performed to maintain radial artery patency at the time of hemostasis , to prevent future radial artery occlusion . © 2008 Wiley‐Liss , Background : Transradial access is the approach of choice in many laboratories for diagnostic coronariography or percutaneous coronary interventions ( PCI ) because of its lower vascular complication rate than the femoral approach . However , this approach has a higher rate ( 5–10 % ) of asymptomatic radial artery ( RA ) occlusion . Methods : We conducted a prospect i ve , controlled , single‐centre trial study . We investigated whether the pneumatic compression ( using “ TR B and of Terumo ® ” ) of the radial artery guided by the mean artery pressure ( MAP ) after the procedure ( group A ) is efficient in reducing radial occlusion in patients under a coronary angiography by transradial access for diagnostic coronariography or PCI compared to use of st and ard procedure ( group B , 15 cm3 of air in the device ) . Results : The study was suspended after analyzing the results of 50 % of the scheduled patients . An analysis of the results of 351 consecutive r and om patients in Group A showed significantly ( P = 0.0001 ) lower rate ( 1.1 % ) of occlusion than Group B ( 12.0 % ) without significant differences in the rate of other complications . Other variables associated with RA occlusion in univariate analysis were previous or active smoker ( P < 0.04 ) , absence of anti‐aggregant treatment ( P < 0.04 ) , and the presence of RA flow postprocedure ( PFP , P < 0.001 ) . Independent predictors with logistic regression analysis were PFP ( HR = 0.06 , 95 % CI 0.01–0.2 ) , presence of hematoma ( HR = 3.7 , 95 % CI 1.2–11.0 ) , and st and ard pneumatic compression in group B patients ( HR = 18.8 , 95 % CI 3.8–92.2 ) . Conclusions : Use of pneumatic compression guided by MAP is safe and efficient , and it can significantly lower the incidence of radial artery occlusion . © 2009 Wiley‐Liss , Background —Compared with transfemoral access , transradial access ( TRA ) for percutaneous coronary intervention is associated with reduced risk of bleeding and vascular complications . Studies suggest that TRA may reduce mortality in patients with ST-segment – elevation myocardial infa rct ion . However , there are few data on the effect of TRA on mortality , specifically , in patients with non – ST-segment – elevation myocardial infa rct ion . Methods and Results —We analyzed 10 095 consecutive patients with non – ST-segment – elevation myocardial infa rct ion treated with percutaneous coronary intervention between 2005 and 2011 in all 8 tertiary cardiac centers in London , United Kingdom . TRA was a predictor for reduced bleeding ( odds ratio=0.21 ; 95 % confidence interval [ CI ] : 0.08–0.57 ; P=0.002 ) , access-site complications ( odds ratio=0.47 ; 95 % CI : 0.23–0.95 ; P=0.034 ) , and 1-year mortality ( hazard ratio [HR]=0.72 ; 95 % CI : 0.54–0.94 ; P=0.017 ) . Between 2005 and 2007 , TRA did not appear to reduce mortality at 1 year ( HR=0.81 ; 95 % CI : 0.51–1.28 ; P=0.376 ) , whereas between 2008 and 2011 , TRA conferred survival benefit at 1 year ( HR=0.65 ; 95 % CI : 0.46–0.92 ; P=0.015 ) . The mortality benefit with TRA at 1 year was not seen at the low-volume centers ( HR=0.80 ; 95 % CI : 0.47–1.38 ; P=0.428 ) but specifically seen in the high volume radial centers ( HR=0.70 ; 95 % CI : 0.51–0.97 ; P=0.031 ) . In propensity-matched analyses , TRA remained a predictor for survival at 1 year ( HR=0.60 ; 95 % CI : 0.42–0.85 ; P=0.005 ) . Instrumental variable analysis demonstrated that TRA conferred mortality benefit at 1-year with an absolute mortality reduction of 5.8 % ( P=0.039 ) . Conclusions —In this analysis of patients with non – ST-segment – elevation myocardial infa rct ion , TRA appears to be a predictor for survival . Furthermore , the evolving learning curve , experience , and expertise may be important factors contributing to the prognostic benefit conferred with TRA Background : The transradial route for coronary intervention has proven to be safe , effective , and widely applicable in different clinical situations . Several compressive hemostatic devices have been introduced that have shown to be safe and are effective in achieving hemostasis . Methods : Seven hundred ninety patients were r and omly assigned to receive either TR b and or Radistop hemostatic compression devices after transradial coronary procedure . The outcome measures were patient tolerance of the device , local vascular complications , and the time taken to achieve hemostasis . Results : The mean age was 62.88 years , and 74.2 % of the patients were men . Patient age , height , weight , wrist circumference , body mass index , male sex , hypertension , diabetes , hypercholesterolemia , and smoking incidences were similar in both groups . There were significantly more patients reporting no discomfort in the TR b and group compared to the Radistop group ( 77 % vs. 61 % ; P = 0.0001 ) . Patients in the Radistop group reported significantly more pain across all categories of severity and three patients in the Radistop group were crossed over to TR b and because of severe discomfort . Oozing and ecchymosis were seen in about 16 % of the patients . Local small hematoma and large hematoma were seen in 5.4 % and 2.2 % patients respectively , and similar in both groups . Radial artery occlusion at the time of discharge was seen in 9.2 % of the patients though only 6.8 % showed persistent occlusion at the time of follow‐up . The time taken to achieve hemostasis was significantly longer in the TR B and group ( 5.32 ± 2.29 vs. 4.83 ± 2.23 hr ; P = 0.004 ) . There was significantly higher incidence of radial artery occlusion in patients with smaller wrist circumference , the patients who experienced radial artery spasm during the procedure , and patients with no heparin administration during the procedure . Conclusions : We have shown in a r and omized comparison of Radistop and TR b and that both devices are safe and effective as hemostatic compression devices following transradial procedures . However , more patients felt discomfort with the Radistop device and the time taken to achieve hemostasis was longer with TR b and . © 2010 Wiley‐Liss , A novel hemostatic device , Adapty ( Medikit , Tokyo , Japan ) , was developed to achieve effective and comfortable hemostasis following transradial procedures . The device consists of a pad fixed to a transparent plastic plate and a self-adhesive strap . The catheter sheath is removed from the radial artery after the pad has been positioned precisely over the puncture site , with the strap attached to the plate . Compression pressure then is adjusted with the self-adhesive strap , as is required with occlusive clamps . Patients do not need to maintain hyperextension of the wrist after the procedure . The wrist can be mobilized immediately after application . The efficacy of Adapty was evaluated in prospect i ve observations of 200 patients . The device was successfully applied in all patients immediately after sheath removal . No patient required interruption of compression because of pain , congestion or ischemia . Complete hemostasis was obtained in 199 patients ( 99.5 % ) , and the device caused no vascular complications . This study demonstrates that Adapty is highly effective for achieving hemostasis after transradial procedures OBJECTIVE Our objective was to evaluate the effectof two different hemostatic devices on radial artery outcomes after transradial catheterization . BACKGROUND Radial artery occlusion is an infrequent but discouraging complication of transradial access . It is related to factors such as sheath-to-artery ratio and its incidence is decreased by the administration of heparin . It usually does not lead to ischemic complications , but precludes future transradial access . PATIENTS AND METHODS 500 consecutive patients undergoing transradial catheterization were prospect ively enrolled in the study . 250 consecutive patients received hemostasis by application of the HemoB and ( Group I ) , and the next 250 patients received hemostasis using the inflatable TR B and ( Group II ) . Radial artery patency was studied at the time of application of the hemostasis device , at 30 minutes , 60 minutes and at 24 hours and 30 days using Barbeau 's test . RESULTS 28 patients in Group I ( 11.2 % ) , developed early occlusion ( at 24 hours ) , compared to 11 patients ( 4.4 % ) in Group II ( p < 0.005 ) . 18 patients in Group I ( 7.2 % ) , developed evidence of chronic occlusion ( at 30 days ) , compared to 8 patients ( 3.2 % ) in Group II ( p < 0.05 ) . Early ( 30 minutes ) return of patency was seen more frequently in Group II using the TR B and compared to Group I using the HemoB and ( 75 % vs. 24 % ; p < 0.001 ) , probably related to a significant early ( 30 minutes ) decrease in TR B and air-chamber pressure . No significant bleeding complication occurred in either group . CONCLUSION A significant reduction in radial artery occlusion was noted with hemostasis using the TR B and compared to the HemoB and , without compromising hemostatic efficacy Objective : To compare bleeding complications and results of percutaneous coronary intervention ( PCI ) between patients treated by radial and femoral approaches for acute myocardial infa rct ion ( AMI , ) and using abciximab and 5 French guiding-catheters . Patients : 114 consecutive patients with AMI were prospect ively r and omised . Exclusion criteria were a history of coronary artery bypass graft , cardiogenic shock , atrioventricular block , and contraindication to abciximab or a negative Allen test . Local haemostasis was achieved by manual compression . Results : Baseline characteristics were similar between the two groups . Peripheral arterial complication rates and delays to patient ambulation were significantly lower in the radial group than in the femoral group , whereas in-hospital stay was similar between the two groups . A cross over was more often necessary in the radial group than in the femoral group . Coronary angiography duration and fluoroscopy time were significantly longer in the radial group than in the femoral group , whereas PCI duration was similar in both groups . Conclusions : The FARMI trial showed that the radial route lowered peripheral arterial complication rates and allowed earlier ambulation , despite no significant benefit on the duration of hospitalisation BACKGROUND Despite the increasing use of transradial techniques for cardiac percutaneous procedures , none of the strategies commonly utilized for hemostasis has been able to reduce the occurrence of radial artery occlusion ( RAO ) . The aim of this study was to evaluate the occurrence of 24-hour RAO and the rate of bleeding of a novel hemostatic device for radial closure after percutaneous interventions , in adjunct to short-time compression . METHODS Once the radial access was obtained , patients were r and omized to 3 different strategies of radial closure : a short compression with the QuikClot ® Interventional ™ pad ( Z-Medica Corporation , Wallingford , CT , USA ) ( 15 minutes , group 1 ) , a short compression ( 15 minutes , group 2 ) , and a conventional prolonged compression ( 2 hours , group 3 ) both without QuikClot ® utilization . RESULTS Fifty patients in group 1 , 20 in group 2 , and 50 in group 3 were enrolled . The three groups were homogenous for baseline and procedural characteristics . None of patients in group 1 developed RAO , 1 ( 5 % ) occurred in group 2 , and 5 ( 10 % ) in group 3 ( P = 0.05 ) . Active bleeding after compression removal occurred in 10 patients ( 20 % ) in group 1 , 18 ( 90 % ) in group 2 , and 1 ( 2 % ) in group 3 ( P < 0.001 ) . Among patients in group 1 , at univariate analysis , the predictors of acute bleeding result ed in chronic therapy with clopidogrel ( Odds Ratio 28.78 , 95 % Confidence Intervals 4.79 - 172.82 , P < 0.001 ) and high levels of activated clotting time ( ACT ) at the time of sheath removal ( OR 1.02 , 95 % CI 1.00 - 1.03 , P = 0.009 ) . At ROC analysis , the cutoff value of ACT for the risk of bleeding with a sensitivity of 80 % and specificity of 75 % was 287 seconds . CONCLUSIONS Early sheet removal and short-time compression with QuikClot ® Interventional ™ can reduce the rate of RAO after diagnostic or interventional procedures especially in patients not on double antiplatelet therapy Coronary angioplasty with 6F guiding catheters via the radial artery is associated with a minimal risk for major entry site-related complications . Although the incidence of radial artery occlusion ( RAO ) in the literature is approximately 30 % after prolonged cannulations , little is known about the incidence and its clinical consequences of RAO following transradial percutaneous coronary angioplasty . In a prospect i ve study , 563 patients with a normal Allen test were evaluated on patency and function of the radial artery after transradial angioplasty , by physical and ultrasound examination at discharge , and at 1 month follow-up . At discharge , 30 patients ( 5.3 % ) had clinical evidence of RAO . At follow-up , persistent RAO was found in 16 patients ( 2.8 % ) . In this study we found a low incidence of RAO after transradial percutaneous coronary angioplasty . None of the patients with temporary or persistent RAO had any major clinical symptoms . Therefore , the occurrence of RAO can be considered a minor complication in patients with a previously good double blood supply to the h and OBJECTIVE To compare the effects of elastic b and age compression with the specific hemostasis devices in patients undergoing transradial coronary intervention . METHODS A total of 3000 consecutive patients were r and omized to 3 groups and 2910 patients completed the study , 963 patients in elastic b and age group ( ER ) , 976 in T b and group ( TB ) and 971 in balloon group ( TR ) . In-hospital vascular related complication was the primary study endpoint . The secondary endpoints included : risk factors of complications , compression time , fibroplasia conditions and the comfort feeling of patients . RESULTS The overall incidence of vascular related complication in 3 groups was similar ( P = 0.262 ) . Female , low body weight , prolongation of procedure and multi-punctures were identified as the independent risk factors for complications . Moreover , the compression time and the fibroplasia condition in TB and TR group were superior to those in the ER group . Comfortable feeling of the patients was better in TR and TB group than in ER group ( P < 0.001 ) . CONCLUSIONS Both conventional b and age device and specific radial device are feasible and associated with low incidence of vascular complication . However , the specific radial device has significant advantage over b and age strategy in compression time and quality of life Recently the transradial route has emerged as a valuable alternative to the femoral approach for coronary angiography and angioplasty . However , sheath and catheter size and their immediate removal after the procedure , combined with aggressive antiplatelet and anticoagulant therapies , have favored mechanical compression of the radial artery to achieve satisfactory hemostasis . We report on our initial clinical experience with a new device specially design ed for prolonged controlled mechanical compression of the radial artery ( the RadiStop radial compression system , RADI Medical Systems AB , Uppsala , Sweden ) . A total of 159 consecutive patients ( mean age 60 + /- 11 yr , 130 males ) who required either coronary angiography ( group 1 , 103 patients ) or ad hoc or elective coronary angioplasty ( group 2 , 56 patients ) via the right radial route had local hemostasis with the RadiStop system . In group 1 , 4F and 5F sheaths and catheters were used , whereas in group 2 , 6F systems were inserted in the radial artery . Hemostasis was achieved with the device in all patients but was considered difficult to obtain in 4 patients ( 2.5 % ) . Twenty-eight patients ( 18 % ) considered the device uncomfortable or painful , but no release of pressure was necessary . The mean compression time was 151 + /- 82 min ( 114 + /- 64 min in group 1 , and 223 + /- 64 min in group 2 ; P = 0.0001 ) . There were 23 local complications ( 15 % ) . In 7 patients ( 4.4 % ) , the radial pulse was absent after compression and at discharge , without major clinical consequences . In one patient , recurrent bleeding occurred 2 hr after compression , requiring a new compression session . In 15 patients , a small local hematoma was observed . Neither heparin dosage nor the use of a 6F sheath affected the rate of radial artery patency in this survey . We conclude that the use of this device for mechanical compression of the radial artery after coronary angiography and angioplasty is efficient , and that its use is related to an acceptable rate of local complications Radial artery occlusion ( RAO ) can result from transradial catheterization . We compared the incidence of RAO with 2 heparin dosage regimens after transradial coronary angiography , and we evaluated the efficacy and safety of transient homolateral ulnar artery compression to achieve acute radial artery recanalization . Patients referred for coronary angiography were r and omized to very-low-dose heparin ( 2,000 IU ) or low-dose heparin ( 5,000 IU ) . On sheath removal , hemostasis was obtained using the TR b and with a plethysmography-guided patent hemostasis technique . In the case of RAO as assessed by duplex ultrasonography 3 to 4 hours after hemostasis , immediate 1-hour ulnar artery compression was applied . Hematomas > 15 cm(2 ) were also assessed . We r and omized 465 patients , 222 in the 2,000-IU group and 243 in the 5,000-IU group . The baseline and procedural characteristics were comparable in both groups . The incidence of initial RAO was 5.9 % in the 2,000-IU group and 2.9 % in the 5,000-IU group ( p = 0.17 ) , with a compression time of 2.10 ± 0.78 hours and 2.25 ± 0.82 hours , respectively ( p = 0.051 ) . After ulnar artery compression , the final incidence of RAO was 4.1 % in the 2,000-IU group and 0.8 % in the 5,000-IU group ( p = 0.03 ) . The incidence of local hematoma was 2.3 % and 3.7 % in the 2,000- and 5,000-IU groups , respectively ( p = 0.42 ) . In conclusion , acute RAO after transradial catheterization can be recanalized by early 1-hour homolateral ulnar artery compression . This simple nonpharmacologic method was effective and safe in patients with very-low- and low-dose heparin . Nevertheless , the incidence of final RAO remained significantly lower after a higher anticoagulation level The frequency of radial artery occlusion was compared between patients receiving 4Fr versus 6Fr transradial coronary interventions ( TRIs ) in an open-label r and omized trial ( Clinical Trials.gov identifier : NCT00815997 ) . The primary outcome measure was radial artery occlusion on the day after TRI . The secondary outcome measures were the procedural success , major advanced cardiac events , access site-related complications , procedural times , fluoroscopy times , and contrast dye usage . A total of 160 patients were included . The procedure was successful in 79 of 80 patients ( 99 % ) in both groups . Whereas the 4Fr group showed no access site-related complications , the 6Fr developed 5 ( 6 % ) , including 3 radial artery occlusions and 2 bleedings ( 1 radial artery perforation and 1 massive hematoma ; p = 0.02 ) . Although the radial artery occlusion rate was lower in the 4Fr versus the 6Fr groups , the difference was not significant ( 0 % vs 4 % , p = 0.08 ) . The mean hemostasis time was significantly shorter in the 4Fr than in the 6Fr groups ( 237 ± 105 vs 320 ± 238 minutes , p = 0.007 ) . In conclusion , these findings suggest that 4Fr TRI may become a less invasive alternative to 6Fr TRI in treating coronary artery diseases |
2,389 | 28,449,307 | Our meta-regression analysis provided the evidence for association between some study covariates with treatment effect , each at different follow-ups .
We concluded that the clinicians can manage post-operative endodontic pain by administration of NSAIDs and /or paracetamol . | The objective of this review was to evaluate the efficacy of non-narcotic analgesics including non-steroidal anti-inflammatory drugs ( NSAIDs ) and /or paracetamol in the treatment of post-operative endodontic pain .
Additionally , we aim ed to examine the possible association of study covariates on the pain scores using meta-regression analysis . | Nonsteroidal antiinflammatory drugs have been used to obtain preemptive analgesia . We investigated , in this r and omized , double-blind study , whether sublingual ( s.l . ) piroxicam given before was more effective than that given after surgery . Fifty-two patients scheduled for laparoscopic bilateral inguinal hernia repair under general anesthesia were enrolled . Group PRE ( 25 patients ) received 40 mg of piroxicam s.l . 2 h before surgery and a placebo 10 min after surgery . Group POST ( 27 patients ) were treated with a placebo 2 h before surgery and received 40 mg of piroxicam s.l . 10 min after surgery . After an initial dose of 100 mg tramadol IV , patient-controlled analgesia with tramadol was started and recorded . Visual analog scores were assessed in the recovery and at 6 , 20 , and 30 h postoperatively . Significantly lower visual analog scores were found in group PRE at 6 and 20 h. Significantly smaller cumulative tramadol consumption was observed after 30 h in group PRE . In summary , our findings suggest that preoperative s.l . piroxicam is more effective than the postoperative administration . Because of the low pain scores in both groups , the clinical relevance of these findings is not clear from this study The purpose of this prospect i ve clinical trial was to investigate the analgesic efficacy of three oral medication groups on postoperative endodontic pain in male and female dental patients , with an emphasis on analgesic differences between the sexes . Forty-three patients were administered ibuprofen 600 mg , placebo , or pentazocine 50 mg/0.5 mg naloxone in a r and omized , double-blinded manner . Beginning immediately after endodontic treatment , patients took the assigned medication every 6 hours for 24 hours and recorded their degree of discomfort on a 100-mm visual analog scale . Statistical analysis of the data showed that ibuprofen 600 mg provided statistically significantly greater analgesia than placebo at 6 and 12 hours ( P = 0.0014 and 0.0024 ) , and pentazocine/naloxone provided statistically significantly greater analgesia than placebo at 12 hours ( P = 0.0084 ) . Sex-dependent differences were noted within the pentazocine/naloxone group , which showed significantly greater analgesia in females compared with males ( P = 0.007 ) Successful management of endodontic pain represents a continuing challenge . The purpose of this r and omized , double-blind , placebo-controlled , parallel-group trial was to compare the pain reducing effect of oral preparations of meloxicam , piroxicam , and placebo in endodontic emergency patients . A total of 51 patients who presented to the Tehran University endodontic clinic and one private dental clinic were invited to participate . Patients were asked to evaluate their pretreatment pain with a visual-analog scale . After root canal therapy they were r and omly assigned to one of three groups : meloxicam , piroxicam , or placebo . Each patient was sent home with a visual-analog scale to fill out at 8 and 24 h after completion of therapy . The results of this study showed no significant differences between efficacy of meloxicam , piroxicam , and placebo , but a significant effect of the time factor in reducing postoperative pain in all treatment groups was observed STUDY OBJECTIVE To determine whether intravenous injection of lornoxicam 30 minutes before skin incision provides better pain relief after varicocelectomy than postoperative administration of lornoxicam . DESIGN Prospect i ve , double-blind , r and omized clinical investigation . SETTING Operating room and postoperative recovery area . PATIENTS 44 ASA physical status I and II adult male patients undergoing varicocelectomy . INTERVENTIONS Patients were r and omized either to receive 8 mg lornoxicam infusion 30 minutes before skin incision , followed by saline infusion immediately after skin closure ( group 1 ) , or to receive the identical injections but in reverse order ( group 2 ) . All patients received local anesthesia with bupivacaine . MEASUREMENTS Postoperative pain scores were evaluated hourly for the first 8 hours after surgery , then at 12 , 16 , 20 , and 24 hours after surgery , using a 10-cm visual analog scale . Time to first analgesic request and patients ' global assessment s also were recorded . MAIN RESULTS Patients in group 1 reported significantly lower pain scores ( P < 0.05 ) at all time intervals except at 24 hours and better global assessment ( P = 0.001 ) than did group 2 . There were significantly fewer patients in the preemptive group than group 2 who required rescue analgesic within the first 24 hours ( 0 % vs 22.7 % ; P = 0.024 ) . Mean time to first analgesic request was also significantly longer in the preemptive group ( P = 0.001 ) . CONCLUSION Intravenous lornoxicam administered before surgery has a better analgesic effect for varicocelectomy than when administered postoperatively Background : Postendodontic pain ( PEP ) has always been a major problem for patients and dentists and NSAIDs are being used to relieve PEP and it is supposed that some benzodiazepines may potentiate facilitate the analgesic effects of the NSAIDs . This study was conducted to evaluate the effect of alprazolam on the analgesic effect of ibuprofen in PEP treatment . Methods : This r and omized double-blind clinical trial was conducted on 45 patients aged 20 - 45 years who were subjected of root canal treatment . A written informed consent was obtained from each patient . The subjects were r and omly divided into three groups ; placebo , ibuprofen ( 400 mg ) and alprazolam ( 0.5 ) mg + ibuprofen ( 400 mg ) . The intensity of pain was recorded using visual analog scale ( VAS ) at 4 , 6 , 12 , 24 , 48 and 72 hours after drug administration . Results : Of the participants , twenty six ( 57.8 % ) were males and 19 patients ( 42.2 % ) were females . Four hours after starting treatment , the VAS scores in the placebo and ibuprofen -treated groups were significantly higher than ibuprofen and alprazolam+ibuprofen groups ( 4.93±1.16 , 3.67±1.88 and 2.67±1.11 , respectively , p<0.0001 ) . The VAS scores in alprazolam + ibuprofen group ( 2.33±1.05 ) were significantly lower at 6 hours after treatment when compared to the other groups ( Ibuprofen : 3.00±1.36 and placebo : 3.08±1.74 , P=0.002 ) . This decrease in VAS score sustained to 12 hours after the start of alprazolam + ibuprofen treatment when compared to ibuprofen or placebo receiving group alone ( p<0.003 ) . The average pain score in female patients who received alprazolam + ibuprofen was significantly lower than males at 12 hours ( 1.3±0.6 v.s 2.14±0.9 , P=0.002 ) and 24 hours after treatment ( 0.88±0.6 v.s 1.86±0.9 , P=0.003 ) . Conclusion : According to the results , it can conclude that alprazolam may enhance the analgesic efficacy of ibuprofen in postendodontic pain To determine if prophylactic etodolac would significantly reduce postendodontic pain , when compared with ibuprofen or placebo , 36 patients consented to single blind oral administration of either 400 mg of etodolac , 600 mg of ibuprofen , or a placebo , before conventional one-appointment root canal therapy . Patient-reported visual analog scale ratings of pain intensity were conducted upon initial clinical presentation , immediately postoperative , 4 , 8 , 12 , 24 , 48 , and 72 h after initiation of root canal therapy . Results showed that prophylactic ibuprofen administration significantly reduced postendodontic pain at 4 and 8 h after initiation of root canal therapy , when compared with etodolac and a placebo . Patients with a periapical diagnosis of acute apical periodontitis or with a Phoenix abscess showed a significant increased need for additional medication after completion of root canal therapy , compared with all other periapical diagnoses Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive – microbial disturbances . Objective To evaluate the role of prophylactic ibuprofen and N-acetylcysteine ( NAC ) on the levels of tumor necrosis factor alpha ( TNF- α ) , interleukin- 6(IL-6 ) and IL-17 and post-treatment pain level in chronic periapical lesions . Material s and methods Eighty patients with chronic apical lesions less than 1 cm were r and omly assigned to receive NAC tablets ( 400 mg ) , ibuprofen tablets ( 400 mg ) , NAC ( 400 mg)/ibuprofen ( 200 mg ) combination and placebo 90 minutes prior to sampling . Periapical exu date s were collected from root canals . TNF- α , IL-6 and IL-17 levels were determined by ELISA and post-treatment pain was assessed using a visual analog scale ( VAS ) . Results There was a significant difference in IL-6 level between ibuprofen group and placebo ( p = 0.019 ) . Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo ( p = 0.043 ) . Four hours after treatment , a significant difference was observed in VAS pain score between ibuprofen group and placebo ( p = 0.017 ) . Eight hours post-treatment , VAS pain score for NAC group was statistically lower than placebo group ( p = 0.033 ) . After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo ( p = 0.049 ) . Conclusion The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exu date s of chronic periapical lesions . On the other h and it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain Achieving successful anesthesia and pain control in a predictable , efficient manner is a challenge in the endodontic treatment of vital inflamed lower molars . The aim of this study was to evaluate the effect of oral ketamine on the dosage of local anesthetics required and postoperative pain management for irreversibly inflamed m and ibular molars . In this r and omized double-blind placebo-controlled clinical trial , 36 patients with irreversibly inflamed m and ibular molars were r and omly divided into two groups of 18 . Ten mg of ketamine dissolved in 20 ml of fruit juice was administered orally to patients in the experimental group . The control group was given 20 ml of fruit juice alone as a placebo . After 30 min , inferior alveolar nerve block ( IANB ) anesthesia was induced using one cartridge of 2 % lidocaine and 1:100000 epinephrine . Teeth were tested after 5 to 10 min using an electrical pulp tester . In patients showing a positive response , another IANB injection was applied , and the total number of anesthetic cartridges used was recorded . Postoperative pain was evaluated using a visual analogue scale ( VAS ) . In addition , use of analgesic in the first 24 h after treatment was monitored using a question naire . Data were analyzed by t test using SPSS software . There were no significant differences in age or gender between the two groups . The number of anesthetic cartridges used in the ketamine group was significantly less than that in the control group ( P = 0.003 ) . Furthermore , postoperative pain in the ketamine group was significantly lower ( P = 0.019 ) . Also the number of analgesic tablets taken in the ketamine group was significantly lower ( P = 0.011 ) . It can be concluded that a low dose of ketamine might be beneficial for enhancing the effect of local anesthetics STUDY OBJECTIVE To determine the optimum time of administration of diclofenac in patients undergoing ambulatory knee arthroscopy : either preoperatively or postoperatively . DESIGN R and omized , double-blind study . SETTING Ambulatory surgical unit in a tertiary referral hospital . PATIENTS 127 ASA physical status I and II patients undergoing ambulatory knee arthroscopy . INTERVENTIONS Patients were r and omized into three groups . The Preop group received 50 mg of potassium diclofenac orally 1 hour preoperatively and a placebo 30 minutes postoperatively . The Pre+postop group received 25 mg of potassium diclofenac 1 hour preoperatively and 25 mg diclofenac 30 minutes postoperatively . The Postop group received a placebo 1 hour before surgery and 50 mg of potassium diclofenac 30 minutes postoperatively . MEASUREMENTS AND MAIN RESULTS The Postop group received a placebo 1 hour preoperatively and 50 mg of potassium diclofenac 30 min postoperatively . Postoperatively , patients used intravenous patient-controlled analgesia ( PCA ) with fentanyl . Total fentanyl consumption was recorded . During the recovery period , pain was assessed using a visual analog scale ( VAS ) at 30-minute intervals . Pain was assessed in both legs at rest , on flexion , and extension of the knee . There were no significant differences in pain scores either at rest or on movement of the operative knee among the Preop , Pre+postop , and Postop groups . The consumption of fentanyl via PCA showed no significant differences among the groups . CONCLUSIONS There is no difference in pain relief whether diclofenac is given preoperatively or postoperatively in patients undergoing unilateral ambulatory knee arthroscopy . Preoperative and postoperative treatment with diclofenac potassium is equally effective The purpose of this prospect i ve research was to evaluate the post-endodontic pain-reducing effect of piroxicam ( feldene ) , a non-selective non-steroidal anti-inflammatory drug . Pain following endodontic treatment is often linked to the inflammatory process as well as additional central mechanisms . The effects of intraligamentary injection of piroxicam have not previously been studied . Sixty-five patients with irreversible pulpitis were r and omly divided into two groups . The active group received intraligamentary injections totalling 0.4 mL of piroxicam , while the placebo group received the same amount of lidocaine . One-appointment endodontic therapy was performed by a single endodontist . Visual Analogue Scale was used to record pain before treatment and 4 , 8 , 12 , 24 and 48 h postoperatively . The decrease in the intensity of post-treatment pain between the two groups was very significant . Intraligamentary injection of piroxicam can be considered an effective method for reducing post-endodontic pain AIM To compare the effects of single doses of three oral medications on postoperative pain following instrumentation of root canals in teeth with irreversible pulpitis . METHODOLOGY In this double-blind clinical trial , 100 patients who had anterior or premolar teeth with irreversible pulpitis without any signs and symptoms of acute or chronic apical periodontitis and moderate to severe pain were divided by balanced block r and om allocation into four groups of 25 each , a control group receiving a placebo medication , and three experimental groups receiving a single dose of either Tramadol ( 100 mg ) , Novafen ( 325 mg of paracetamol , 200 mg ibuprofen and 40 mg caffeine anhydrous ) or Naproxen ( 500 mg ) immediately after the first appointment where the pulp was removed , and the canals were fully prepared . The intensity of pain was scored based on 10-point VAS before and after treatment for up to 24 h postoperatively . Data were su bmi tted to repeated analysis of variance . RESULTS At the 6 , 12 and 24 h postoperative intervals after drug administration , the intensity of pain was significantly lower in the experimental groups than in the placebo group ( P < 0.01 ) . Tramadol was significantly less effective ( P < 0.05 ) than Naproxen , and Novafen that were similar to each other ( P > 0.05 ) . CONCLUSION A single oral dose of Naproxen , Novafen and Tramadol taken immediately after treatment reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis This double-blind study compared a controlled-release formulation of ibuprofen 600 mg with three doses of regular ibuprofen 200 mg and three doses of codeine 30 mg . Patients who had dental impaction surgery received the controlled-release ibuprofen , codeine , or regular ibuprofen when postoperative pain reached moderate to severe intensity . At 4 and 8 hours after dose 1 , patients who had initially received the controlled-release ibuprofen received a placebo , and those taking ibuprofen and codeine received their second and third doses of those drugs . All doses of study medication or placebo appeared identical for each treatment . Subjects made evaluations hourly for 12 hours in a diary . The controlled-release ibuprofen had a comparable onset to ibuprofen , a higher peak effect , and was significantly more effective than ibuprofen at hour 4 ; the controlled-release ibuprofen was significantly more effective than codeine for all hourly observations through hour 9 . Ibuprofen was significantly better than codeine only through hour 3 . The controlled-release ibuprofen had the lowest incidence of side effects and codeine the highest . The single dose of the controlled-release ibuprofen formulation appeared as efficacious as three regular doses of ibuprofen 200 mg over a 12-hour period This study compares single-dose ibuprofen pretreatment for postoperative endodontic pain . Thirty-nine emergent patients were r and omly assigned to 3 groups : placebo , ibuprofen tablets , or ibuprofen liquigels . Patients recorded their pain levels before and at the end of treatment , then every 6 hours for 24 hours after administration of the medications and st and ard endodontic treatment . Pain evaluations by using 3 pain scales ( visual analog scale [ VAS ] , category , and Heft-Parker ) were highly correlated , suggesting the rationale for only using one pain scale in pain studies . No significant differences in postoperative pain levels were found between either single-dose ibuprofen formulation or the placebo control group ( P = .84 ) . Patients treated with calcium hydroxide versus obturation did not differ in postoperative pain levels ( P = .44 ) . This study suggests that single-dose pretreatment analgesia alone in endodontic pain patients will not significantly reduce postoperative pain below the reduction in pain from endodontic treatment AIM To compare ibuprofen , to an ibuprofen/acetaminophen combination in managing postoperative pain following root canal treatment . It is hypothesized that the drug combination will provide more postoperative pain relief than the placebo or ibuprofen alone . METHODOLOGY Patients presenting at the Texas A&M Baylor College of Dentistry 's graduate endodontic clinic , experiencing moderate to severe pain , were considered potential c and i date s. Fifty-seven patients were included based on established criteria . Following administration of local anaesthesia , a pulpectomy was performed . The patients were administered a single dose of either : ( i ) placebo ; ( ii ) 600 mg ibuprofen ; or ( iii ) 600 mg ibuprofen and 1000 mg of acetaminophen . Patients recorded pain intensity following treatment on a visual analogue scale and a baseline four-point category pain scale as well as pain relief every hour for the first 4 h then every 2 h thereafter for a total of 8 h. A general linear model ( GLM ) analysis was used to analyse the outcome . RESULTS Based upon the GLM analysis , there was a significant difference between the ibuprofen and the combination drug group , and between placebo and combination drug groups . There was no significant difference between the placebo and the ibuprofen . CONCLUSION The results demonstrate that the combination of ibuprofen with acetaminophen may be more effective than ibuprofen alone for the management of postoperative endodontic pain The ability of intracanal use of two nonsteroidal anti-inflammatory agents -- diclofenac and ketoprofen -- with and without hyaluronidase to control posttreatment pain was compared with that of a placebo control in a double-blind study of 760 subjects . The study was carried out on originally asymptomatic and symptomatic teeth that required endodontic therapy . Endodontic treatment was completed in three visits during which medications were placed into the canal either at the end of the first visit ( postextirpation ) or the second visit ( postinstrumentation ) . Patients subjectively rated their pain on a scale of 1 to 4 as none , mild , moderate , and severe . The ratings were done preoperatively and at 2 , 4 , 8 , and 12 hours postoperatively on the first day as well as on the second and third days . Statistical analysis of the data revealed that both diclofenac and ketoprofen significantly reduced the mean pain score in originally asymptomatic and symptomatic cases and were significantly superior to the placebo until the end of the study . Postendodontic pain occurred with less frequency when the teeth were treated with diclofenac , but diclofenac-treated and ketoprofen-treated cases were not significantly different at controlling postendodontic pain . An increase in the number of patients who reported complete absence of pain was recorded when hyaluronidase was added to the study medications . However , the difference between the medications and medications-hyaluronidase was not of statistical significance Effective management of endodontic pain represents a continuing challenge . In this study , we evaluated the efficacy of flurbiprofen and a novel central ly acting analgesic , tramadol , alone and in combination , for reducing pain in endodontic emergency patients . Patients ( n = 49 ) were administered a local anesthetic and underwent pulpectomy . They were then administered , on a double-blind basis , either : ( i ) placebo ( one capsule to start and then every 6 h ) ; ( ii ) flurbiprofen ( 100 mg loading dose and then 50 mg every 6 h ) ; ( iii ) tramadol ( 100 mg loading dose and then 100 mg every 6 h ) ; or ( iv ) the combination of flurbiprofen and tramadol ( as above ) . Pulpectomy combined with placebo medication result ed in a 50 % reduction in pain by 24 h ( p < 0.01 ) . Patients treated with flurbiprofen and tramadol reported less pain , compared with placebo treatment at 6 and 24 h ( p < 0.01 for both ) . These results suggest that a nonsteroidal anti-inflammatory drug/opiate combination , together with endodontic therapy , may be useful in the management of endodontic pain The purpose of this study was to evaluate clinical ly the effectiveness of preoperatively administered flurbiprofen , a nonsteroidal anti-inflammatory drug , in suppressing postendodontic treatment pain . Sixty symptomatic and 60 asymptomatic patients were equally distributed into four groups : dose 30-min preoperatively — group A ( control ) , placebo ; group B , placebo ; group C , flurbiprofen ( 100 mg ) ; and group D , flurbiprofen ( 100 mg ) and postoperative medication — group A , placebo ; group B , flurbiprofen ( 100 mg ) , group C , placebo ; and group D , flurbiprofen ( 100 mg ) . Each patient received preoperative medication or placebo , local anesthetic , initial root canal debridement , and finally a postendodontic medication or placebo in a double-blind manner . Pain was quantified by self-report of the patient with three different scales : ( 1 ) category rating , ( 2 ) visual analogue , and ( 3 ) pain relief . Observations were recorded immediately before and after instrumentation , and at 3 ( time of postendodontic dose ) , 7 , and 24 h after the first dose of medication . The data were statistically analyzed . For patients who were symptomatic before treatment , the preoperative administration of flurbiprofen plus endodontic treatment significantly reduced postoperative pain . At 7 and 24 h , symptomatic patients who received medication reported less pain as compared with patients who received a placebo in five of the six comparisons . There was a low incidence of postendodontic pain regardless of drug therapy when the patient was asymptomatic at the start of therapy . The difference in the occurrence rate of side effects between the four groups was not significant . The informed consent of all human subjects who participated in the experimentalinvestigation(s ) reported or described in this article was obtained after the nature of the procedures and possible discomforts and risks had been fully explained . Flurbiprofen is approved for experimental use under FDA regulation is aPhase III drug . The IND is held by The Upjohn Co. , Kalamazoo , MI . The Upjohn Company provided no financial support for this study . The opinions expressed herein are those of the authors and are not to be construed as those of the Department of the Navy or the Department of Defense The ability of two nonsteroidal anti-inflammatory agents -- piroxicam and diclofenac -- to control endodontic pain was compared with that of a placebo control in a double-blind study of 267 patients requiring endodontic therapy . Endodontic treatment was carried out over three visits with an interval of 5 to 7 days between each two consecutive visits . All patients were clearly instructed to take the medication only if they experienced pain , between the visits or postoperatively , for 3 consecutive days . The patients subjectively rated their pain on a scale of 1 to 4 as none , mild , moderate , or severe . The ratings were done preoperatively and at 2 , 4 and 8 hours after the initial dose of medication was taken , as well as on the second and third days . Statistical analysis of the data revealed that both piroxicam and diclofenac significantly reduced the mean pain score at the end of all observations and were significantly superior to the placebo until the end of the study . More than 90 % of the patients treated with piroxicam and more than 80 % of the patients treated with diclofenac showed complete relief of pain . Overall , piroxicam was clearly more effective than diclofenac or the placebo . It provided more consistent relief of pain , beginning 2 hours after the initial dose , and it continued to do so at every interval thereafter . Diclofenac required longer time to reach maximum effectiveness . Piroxicam 's superiority was greater at the first and second days after the initial dose of medication was taken . With respect to side effects , piroxicam was better tolerated by the patients . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study was to determine if prophylactic rofecoxib would significantly reduce postendodontic pain , when compared with ibuprofen or placebo . An additional objective was to establish if any relationship exists between periapical diagnosis and the need for additional medication after completion of pulpectomy . A total of 45 patients consented to a double-blind , single-dose oral administration of 50 mg of rofecoxib , 600 mg of ibuprofen , or a placebo before conventional root canal therapy . The root canal treatment was performed in two appointments . Patient-reported visual analog scale ratings of pain intensity were conducted upon initial clinical presentation and at 4 , 8 , 12 , 24 , 48 , and 72 h after completion of pulpectomy . Results showed that at the 4- and 8-h periods , both rofecoxib and ibuprofen provided significantly better pain relief than placebo . At the 12- and 24-h periods , rofecoxib demonstrated significantly better pain relief than both ibuprofen and placebo . Patients with a periapical diagnosis of acute apical periodontitis showed a significantly increased need for additional medication after completion of pulpectomy compared with all other periapical diagnoses OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful BACKGROUND Tonsillectomy is commonly performed in children , but unfortunately it is associated with intense postoperative pain . The use and optimal timing of nonsteroidal anti-inflammatory drugs ( e.g. ketoprofen ) during tonsillectomy is controversial . METHODS We evaluated the safety and efficacy of ketoprofen in 109 children , aged 3 - 16 years , during and after tonsillectomy in 1998 - 2000 . St and ardized anaesthesia was used . Forty-seven children received ketoprofen 0.5 mg.kg-1 at induction ( preketoprofen group ) and 42 children after surgery ( postketoprofen group ) , followed by continuous ketoprofen infusion of 3 mg.kg-1 over 24 h in both groups ; 20 children received normal saline ( placebo group ) . Oxycodone was used for rescue analgesia . RESULTS Pre- and postketoprofen groups did not differ in experienced pain or in opioid consumption in the first 24 h after surgery ; demonstrating that ketoprofen did not have a pre-emptive effect . Patients in the placebo group received 30 more oxycodone doses than did patients in the ketoprofen groups , but the difference was not significant ( P=0.074 ) . Two patients ( 5 ) in the postketoprofen group had postoperative bleeding at 4 h and 26 h , respectively . Both patients required electrocautery to stop bleeding . Neither the incidence nor the severity of adverse events differed between study groups . CONCLUSIONS This study demonstrates that ketoprofen did not have a preemptive effect and , at the dose used , did not perform statistically significantly better than placebo |
2,390 | 18,946,610 | In the two trials with subjects having moderate to high risk for progressive disease , MMF did not demonstrate any significant difference in retarding the decline in renal function and proteinuria reduction .
CONCLUSION No benefit was seen in moderately-advanced IgAN treated with MMF .
In a selected group of patients with less advanced disease , MMF was effective in proteinuria reduction . | INTRODUCTION The aim of this study was to determine the effectiveness of mycophenolate mofetil ( MMF ) in IgA nephropathy ( IgAN ) . | BACKGROUND Membranous nephropathy is a common cause of nephrotic syndrome ( NS ) in adults . Its treatment is still under debate . METHODS We report our experience in a pilot study using initially low doses of steroids and tacrolimus ( Tac ) . After 3 months of treatment , mycophenolate mofetil ( MMF ) was added if the proteinuria was higher than 1 g/day . RESULTS In accordance with this st and ard , 21 patients entered the study . A proteinuria level lower than 1 g/day was reached at month 3 of therapy with steroids and Tac in 11 patients . These patients continued this treatment for 12 months . MMF was added in nine cases after the third month and triple therapy was maintained for 12 more months . Two patients were withdrawn because of side effects . At the end of the treatment , remission of the NS was present in 15 out of all the patients ( 71.4 % ) . Remission of the NS was complete in eight ( 53.3 % ) patients and partial in seven ( 46.7 % ) others . The remaining four patients did not respond . There were no significant changes in renal function . At a mean time of 23.1 months after treatment was discontinued , 11 ( 73.3 % ) patients had relapsed . CONCLUSIONS In this trial , treatment with tacrolimus showed a good efficacy but a high relapse rate when it was discontinued BACKGROUND Because humoral immunity is believed to play a pivotal role in the pathogenesis of IgA nephropathy ( IgAN ) , a prospect i ve placebo-controlled r and omized study was started in patients with IgAN using mycophenolate mofetil ( MMF ) . METHODS A total of 34 patients with IgAN were treated with salt intake restriction , angiotensin-converting enzyme ( ACE ) inhibition and MMF 2 g per day ( N= 21 ) or placebo ( N= 13 ) . After 36 months of follow-up clinical , biochemical , and radiologic data were analyzed using linear mixed models for longitudinal data and Kaplan-Meier survival analysis . RESULTS Therapy had to be stopped prematurely in five patients . Two patients ( MMF group ) evolved to end-stage renal disease ( ESRD ) . There was no difference between groups in the percentage of patients with a decrease of 25 % or more in the inulin clearance or with a serum creatinine increase of 50 % or more over 3 years . There was also no significant difference between groups in annualized rate of change of serum creatinine , computed by linear regression analysis . No significant difference was noted between groups for inulin clearance , serum creatinine , proteinuria , blood pressure , or other parameters of renal function . Hemoglobin and C-reactive protein were significantly lower in the MMF group compared with the placebo group . As a function of time , a significant decline in both groups was noted of proteinuria , parenchymal thickness of the kidneys and C3d . CONCLUSION In patients with IgAN at risk for progressive disease , no beneficial effect of 3-year treatment with MMF 2 g per day could be demonstrated on renal function/ outcome or proteinuria . However , larger r and omized studies are needed to confirm or reject these results BACKGROUND The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation . The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy . METHODS In a multicenter , placebo-controlled , r and omized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria . The daily dose of fish oil was 12 g ; the placebo was a similar dose of olive oil . Serum creatinine concentrations , elevated in 68 percent of the patients at base line , and creatinine clearance were measured for two years . The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study . RESULTS Fifty-five patients were assigned to receive fish oil , and 51 to receive placebo . According to Kaplan-Meier estimation , 3 patients ( 6 percent ) in the fish-oil group and 14 ( 33 percent ) in the placebo group had increases of 50 percent or more in their serum creatinine concentrations during treatment ( P = 0.002 ) . The annual median changes in the serum creatinine concentrations were 0.03 mg per deciliter ( 2.7 mumol per liter ) in the fish-oil group and 0.14 mg per deciliter ( 12.4 mumol per liter ) in the placebo group . Proteinuria was slightly reduced and hypertension was controlled to a comparable degree in both groups . The cumulative percentage of patients who died or had end-stage renal disease was 40 percent in the placebo group after four years and 10 percent in the fish-oil group ( P = 0.006 ) . No patient discontinued fish-oil treatment because of adverse effects . CONCLUSIONS In patients with IgA nephropathy , treatment with fish oil for two years retards the rate at which renal function is lost In several studies diets supplemented with fish oil containing a high proportion of omega-3-polyunsaturated fatty acids ( w-3-PUFA ) have been shown to produce beneficial effects , such as a reduction in blood pressure , lipid levels and inflammation , all of which may affect the course of IgA nephropathy . However , the results of hitherto published studies concerning IgA nephropathy have been inconclusive . We therefore carried out a prospect i ve , r and omized , placebo-controlled six-month study with a higher daily dose of w-3-PUFA than used in previous studies . Thirty-two adult patients with biopsy-proven IgA nephropathy and proteinuria completed the study : 15 were assigned to a fish-oil product with a high percentage of w-3-PUFA ( K 85 , with 55 % eicosapentenoic and 30 % docosahexenoic acid ) and 17 to corn oil , 6 g daily of either oil . At the start , no significant differences were found between the two groups ( K85 : 3 females/12 males , mean age 39 years ( range 22 - 64 ) , corn oil : 4 females/13 males , age 42 years ( range 26 - 68 ) . By six months , supplements of K85 result ed in a slight but significant reduction in glomerular filtration rate ( GFR ) compared to the start : 51Cr-EDTA : 63 + /- 22 to 59 + /- 21 ml/min/1.73 m2 ( p < 0.05 ) , creatinine clearance : 91 + /- 31 to 79 + /- 25 ml/min ( p < 0.01 ) , s-creatinine : 131 + /- 39 to 139 + /- 39 mumol/l , whereas no change in GFR was observed in the corn oil group . The urinary total protein and red blood cell excretions were not affected in any of the groups . ( ABSTRACT TRUNCATED AT 250 WORDS A multicentre , r and omized , placebo-controlled study was performed in 39 adult patients with biopsy-proven IgA nephropathy with the aim of comparing the effects of the ACE inhibitor fosinopril and placebo on proteinuria . All patients had normal blood pressure and normal renal function . Proteinuria ranged from 1.0 to 2.5 g/24 h. After a 3-month run-in period , fosinopril and placebo were r and omly administered in two 4-month sequences separated from cross-over treatment by a 1-month interval . The mean values of creatinine clearance did not change during either the placebo or the treatment sequences . The mean values of mean arterial pressure ( MAP ) were significantly lower during the fosinopril sequence ( 90.4 + /- 9.0 mmHg ) than in basal conditions ( 92.8 + /- 9.1 mmHg ) ( P = 0.034 ) . The mean basal values of proteinuria were 1.74 + /- 0.84 g/24 h. They were unchanged during the placebo sequence ( 1.79 + /- 1.20 ) and fell to 1.37 + /- 0.98 g/24 h after 4 months of fosinopril treatment . Using a multivariate statistical analysis , the treatment effect by time on proteinuria was significantly evident only in the fosinopril sequence ( Wilks test , P = 0.033 ) . Changes in protein excretion were not correlated with changes in MAP , baseline plasma renin activity , and urinary sodium excretion . This controlled study shows that fosinopril can significantly reduce proteinuria even in normotensive patients with IgA nephropathy . Obviously , the results of treatment with ACE inhibitors on long-term renal prognosis remain to be eluci date BACKGROUND Treatment of primary glomerular diseases may be unsuccessful or have potential toxicities . Therefore , we evaluated the use of mycophenolate mofetil ( MMF ) for empirical treatment of primary glomerulopathies . METHODS Forty-six patients with biopsy-proven primary glomerulopathies received MMF for > or =3 months as adjunctive or primary treatment . Median ( range ) 24-hour urine protein to creatinine ratio ( Up/c ) and serum creatinine at the start and end of MMF therapy were compared using the Wilcoxon signed-ranks test . RESULTS Overall , the median Up/c decreased from 4.7 ( range < 0.1 , 20.3 ) to 1.1 ( < 0.1 , 14.3 ; P < 0.001 ) at the end of MMF treatment with no significant change in median serum creatinine 1.3 ( 0.6 to 6.1 ) to 1.2 ( 0.5 to 6.5 ) mg/dL. Median serum albumin increased from 3.4 ( 1.4 , 4.6 ) to 4.1 ( 1.7 , 48 ) g/dL ( P < 0.001 ) and the median serum cholesterol decreased from 270 ( 148 , 795 ) to 220 ( 140 , 309 ) mg/dL ( P < 0.001 ) post-treatment . For those with minimal change disease , a complete steroid withdrawal was accomplished in 5/6 steroid dependent patients . Focal segmental glomerulosclerosis ( FSGS ) patients had a median Up/c that decreased from 2.7 ( 0.1 , 20.3 ) to 0.8 ( < 0.1 , 8.2 ; P = 0.001 ) in 18 patients . In membranous nephropathy ( MN ) patients , the median Up/c decreased from 7.3 ( 0.1 , 18.5 ) to 1.5 ( < 0.1 , 14.3 ) ( P = 0.001 ) in 17 patients . No significant change in median serum creatinine was detected in FSGS or MN patient groups during treatment . CONCLUSIONS Empirical MMF therapy in the majority of patients with primary glomerulopathies was well tolerated and achieved the goals of steroid withdrawal , improvement of nephrotic syndrome , and stabilization of renal function BACKGROUND The therapy of nephrotic syndrome in focal segmental glomerulosclerosis ( FSGS ) is still a matter of controversy . METHODS We performed a prospect i ve r and omized study of the treatment of nephrotic syndrome due to FSGS . We compared 2 specific treatment protocol s to assess the effect of treatment on proteinuria and renal function . Fifty-seven patients were r and omly assigned to 2 groups : group 1 ( n = 34 ) received steroids and cyclosporine , and group 2 ( n = 23 ) received steroids and chlorambucil for 6 months . When treatment was refractory to chlorambucil , the patients in this group were treated with cyclosporine . Creatinine , blood urea nitrogen , proteinuria , lipids , and arterial hypertension were monitored at regular intervals . RESULTS Patients showed a mean serum creatinine of 1.5 + /- 0.2 mg/dL ( 132.6 + /- 17.7 micromol/L ) and proteinuria of 4.8 + /- 2.8 g/24 h with no differences between the groups . At the end of the chlorambucil therapy , patients in group 2 had creatinine levels of 1.8 + /- 0.6 mg/dL ( 159.1 + /- 53 micromol/L ) and proteinuria levels of 3.4 + /- 1 g/24 h. All patients in this group were given cyclosporine . After 4 years the mean creatinine level in group 1 was 1.7 + /- 0.4 mg/dL ( 150.3 + /- 35.4 micromol/L ) and the proteinuria level was 2.5 + /- 1 g/24 h. In group 2 , the mean creatinine level was 1.9 + /- 0.6 mg/dL ( 168 + /- 53 micromol/L ) ( not significant [ NS ] ) and the mean proteinuria level was 2.3 + /- 1.1 g/24 h ( NS ) . Full remission occurred in 23 % of the patients in group 1 ( n = 8) and 17 % of the patients in group 2 ( n = 4 ; NS ) . Partial remission was observed in 38 % of the patients in group 1 ( n = 13 ) and 48 % in group 2 ( n = 11 ; NS ) . The number of patients who developed end-stage renal disease was comparable in both groups : 4 of 34 patients in group 1 after 2.5 + /- 0.8 years , and 5 of 23 patients in group 2 ( NS ) . CONCLUSION Additional treatment with chlorambucil was found to be ineffective in FSGS . Patients responded to treatment with steroids or cyclosporine , but additional treatment with chlorambucil did not improve the patient 's outcome . Future studies must focus on the long-term prognosis of these patients BACKGROUND Cyclophosphamide can decrease proteinuria and improve renal function in patients with idiopathic membranous nephropathy , but has a high risk of side effects . We studied whether mycophenolate mofetil ( MMF ) could be a reasonable alternative with fewer side effects . STUDY DESIGN Clinical trial with historic controls . SETTING S & PARTICIPANTS 32 cases and 32 controls with idiopathic membranous nephropathy and renal insufficiency at multiple centers . For comparison , we selected matched historic controls treated with cyclophosphamide . INTERVENTION MMF , 1 g twice daily , for 12 months versus cyclophosphamide , 1.5 mg/kg/d , for 12 months . Both groups also received intermittent methylprednisolone and alternate-day prednisone . OUTCOMES & MEASUREMENTS Serum creatinine , proteinuria , and side effects during and after treatment . RESULTS Median follow-up was 23 months ( range , 11 to 46 months ) . Median serum creatinine levels were 1.8 mg/dL ( 159 micromol/L ) in both groups at baseline and 1.4 mg/dL ( 124 micromol/L ) in the MMF group versus 1.3 mg/dL ( 115 micromol/L ) in the cyclophosphamide group at 12 months ( P = 0.4 ) . Proteinuria values at baseline and 12 months were protein of 8.40 and 1.41 g/d in the MMF group versus 9.19 and 1.13 g/d in the cyclophosphamide group ( P = 0.5 at 12 months ) , respectively . Cumulative incidences of remission of proteinuria at 12 months were 66 % in the MMF group versus 72 % in the cyclophosphamide group ( P = 0.3 ) . Five patients ( 16 % ) in the MMF group versus none in the cyclophosphamide group had disease that did not respond to therapy ( P = 0.05 ) . Twelve patients ( 38 % ) experienced a relapse and 9 patients ( 31 % ) were re-treated in the MMF group compared with 4 ( 13 % ) and 2 patients ( 6 % ) in the cyclophosphamide group ( P < 0.01 and P = 0.024 , respectively ) . Side effects occurred in 24 patients ( 75 % ) in the MMF group and 22 patients ( 69 % ) in the cyclophosphamide group ( P = 0.6 ) . LIMITATIONS Nonr and omized control group , short duration of follow-up . CONCLUSIONS A 12-month course of MMF decreased proteinuria and improved renal function in the majority of patients , but did not appear as effective or better tolerated than cyclophosphamide . Long-term data and r and omized controlled trials are needed to ascertain the efficacy of MMF in patients with idiopathic membranous nephropathy Mycopehenolate mofetil ( MMF ) is a powerful immunosuppressant that inhibits the proliferation of T and B lymphocytes by blocking the enzyme inosine monophosphate dehydrogenase . MMF has been shown to prevent acute graft rejection in animal experiments and may have an important role in clinical renal transplantation . We conducted a prospect i ve , double-blind , multi-center trial to compare the efficacy and safety of MMF and azathioprine within st and ard immunosuppressive regimen for patients receiving a first or second cadaveric renal graft . A total of 503 patients were r and omized to groups receiving MMF 3 g ( n=164 ) , MMF 2 g ( n=173 ) , or azathioprine ( AZA ) 100 - 150 mg ( n=166 ) daily . All were treated simultaneously with equivalent doses of cyclosporine and oral corticosteroids and followed for 12 months . The primary endpoint was treatment failure , defined as the occurrence of biopsy-proven graft rejection , graft loss , patient death , or discontinuation of the study drug during the first 6 months after transplantation . Treatment failure occurred in 50.% of patients in the AZA group by 6 months after transplantation , compared with 34.8 % in the MMF 3 g group ( P=0.0045 ) and 38.2 % in the MMF 2 g group ( P=0.0287 ) . Biopsy-proven rejection occurred in 15.9 % of patients in the MMF 3 g group and 19.7 % in the MMF2 g group , compared with 35.5 % in the AZA group . Rejection of histologic severity grade II or more developed in 6.1 % , 10.4 % and 19.9 % of patients in the MMF 3 g , MMF 2 g , and AZA groups , respectively . Patients receiving MMF required less frequent and less intensive treatment for acute rejection : 24.4 % of patients on MMF 3 g and 31.0 % on MMF 2 g were tested for acute rejection , compared with 47.5 % on AZA . Only 4.9 % on MMF 3 g and 8.8 % on MMF 2 g required antilymphocyte antibodies for treatment of severe or steroid-resistant rejection , compared with 15.4 % of the patients on AZA . At 1 year after transplantation , graft survival in the MMF groups was marginally superior to that in the AZA group , although this difference was not statistically significant . Gastrointestinal toxicity and tissue-invasive cytomegalovirus infection were more common in the MMF 3 g group . Noncutaneous malignancies occurred in six patients on MMF 3 g , three patients on MMF 2 g , and four patients on AZA . Lymphoproliferative disorders occurred in two patients per MMF group , compared with one patient receiving AZA . MMF appears to be an important advance in prophylaxis following renal transplantation . It is associated with a significantly lower rate of treatment failure compared with AZA during the first 6 months after renal transplantation and produces a clinical ly important reduction in the incidence , severity , and treatment of acute graft rejection . These differences persist throughout the first year of follow-up . Clinical benefit was greatest with a dose of MMF 3 g/day , but gastrointestinal effects , invasive cytomegalovirus infection , and malignancies were slightly more common at that dose . The appropriate dose may lie between 2 g and 3 g per day and may require individualization depending on clinical course or other factors OBJECTIVE To investigate the effectiveness safety and tolerance of mycophenolate mofeil(MMF ) in severe IgA nephropathy and evaluate the dosage adjustment and course for clinical treatment . METHODS 62 patients with IgA nephropathy diagnosed by renal biopsy as Lee 's grade IV and V with urinary protein > 2.0 g/d were enrolled r and omly in the trial . The initial dosage of MMF was 1.0 g/d ( body weight < 50 kg ) or 1.5 g/d ( body weight > 50 kg ) . The dosage was reduced to 0.75 approximately 1.0 g/d after 6 months treatment , the maintaining dosage was 0.5 approximately 0.75 g/d after 12 months . The total course of treatment lasted at least 12 months . Another 31 patients matched with age gender and severity of renal damage were given prednisone orally ( 0.8mg(;)kg(;)d ) ( control group).Blood and urinary tests hepatic and renal function plasma albumin serum triglyceride and cholesterol 24 h protein excretion urinary NAG enzyme , creatinine clearance(Ccr ) were performed before and 3 6 12 18 months after treatments in both groups 5 patients in MMF group received repeated renal biopsy . RESULTS ( 1 ) After 3 months treatment , decrease of urinary protein ( 1.9 g/24 h + /- 1.6 g/24 h vs 3.2 g/24 h + /- 1.7 g/24 h , P < 0.01 ) and improvement of plasma albumin ( 41 g/L + /- 6 g/L vs 37 g/L + /- 6 g/L , P < 0.01 ) were observed in MMF groups while in control group , no significant changes were found in uinary protein ( 2.3 g/24 h + /- 1.8 g/24 h vs 2.9 g/24 h + /- 1.5 g/24 h , P < 0.05 ) and plasma albumin ( 40 g/L + /- 6 g/L vs 37 g/L + /- 6 g/L , P < 0.05 ) . After treatment for 6 , 12 and 18 months , both group showed obvious alleviation of proteinuria and albumin . At the 12th and 18th month , the proteinuria in MMF group was significantly improved than that in control group ( 0.8 g/24 h + /- 0.8 g/24 h vs 1.4 g/24 h + /- 1.6 g/24 h and 0.6 g/24 h + /- 0.7 g/24 h vs 1.4 g/24 h + /- 1.3 g/24 h , P < 0.05 respectively ) . The remission rate and total effective rate of MMF group were higher than those of the control group ( 44.4 % vs 19.1 % and 88.9 % vs 61.9 % , P < 0.05 respectively ) . Patients were administered with MMF for 13.8 + /- 6.3 months ( 6 approximately 30 m ) . ( 2 ) Serum cholesterol and triglyceride were remarkably reduced after 6,12 and 18 months treatment in MMF group , no significant difference was found in control group(P < 0.05 ) . ( 3 ) For the 6 patients with renal insufficiency in MMF group , MMF treatment was significantly effective in 1 patient , effective in 2 patients , not effective in 3 patients with an overall effective rate of 50 % . For the 7 patients with renal insufficiency in control group , the treatment was significantly effective in 1 patient , effective in 1 patient , not effective in 5 patients and total effective rate is 28.6 % . ( 4 ) 5 patients in MMF group received repeated renal biopsy after 7 approximately 12 months treatment ( mean 9.8 + /- 2.3 m ) . The results showed that the interstitial lesions were alleviated . No special drug-induced renal damage was obtained . ( 5 ) Side effects : 3 patients in MMF group suffered from slight diarrhea , 1 patient herpes zoster , all of them got remission without drug withdrawal . 1 patient suffered nausea in the first weeks . No significant change was found in hepatic function ( P > 0.05 ) . CONCLUSIONS MMF is more effective in reducing proteinuria and serum lipid than the currently widespread use of prednisone therapy in IgA nephropathy patients with Lee SMK 's grade IV approximately V and urinary protein > 2.0 g/d . Treatment with MMF associates with less adverse effect and good tolerance BACKGROUND IgA nephropathy ( IgAN ) is the most common form of glomerulonephritis worldwide . Up to 40 % progress to end-stage renal disease ( ESRD ) over 10 - 20 years . Currently , treatment is limited . We studied the use of mycophenolate mofetil ( MMF ) vs placebo in a group of North American IgAN patients at high risk for progressive disease . METHODS Included were 32 patients aged 18 - 75 years from multiple centres who had their biopsies read at Columbia and who had at least 1 g of proteinuria per day plus at least two of the following risk factors : ( i ) male sex ; ( ii ) hypertension > 150/90 mmHg or requiring antihypertensive medications ; ( iii ) creatinine clearance , measured by 24 h urine collection , < 80 and > 20 ml/min at time of enrolment ; and ( iv ) presence of glomerulosclerosis or tubulointerstitial atrophy and fibrosis on renal biopsy . Patients were r and omized to either 1 year of MMF , titrated up to a dose of 1000 mg bid , or placebo . Total follow-up was 2 years . All patients received angiotensin inhibition medication . The primary outcome was a 50 % increase in baseline serum creatinine ( SCr ) . Secondary outcomes were an increase of 0.5 mg/dl SCr , ESRD and a 50 % reduction in proteinuria . RESULTS The mean baseline SCr was 2.4 mg/dl . No statistically significant differences were observed for any outcome . Five of 17 who received MMF vs two of 15 patients in the placebo group reached a 50 % increase in SCr ( P = 0.4 ) . In both groups , all patients who reached the primary outcome also reached ESRD . Ten who received MMF vs seven who received placebo had a 0.5 mg/dl increase in SCr ( P = 0.7 ) Only three MMF and two placebo patients had a 50 % reduction in 24 h proteinuria . No serious adverse events occurred in either group . CONCLUSION No benefit was seen in patients who received MMF in this high risk group , probably reflecting the relatively advanced stage of disease of our population . We conclude that MMF is probably not effective in patients with IgAN who already have moderate renal insufficiency Thirty-seven patients with biopsy proven mesangial IgA nephropathy were prospect ively allocated to either two years of treatment with eicosapentanoic acid ( EPA ) 10 g per day or no treatment . At entry treated and untreated patients with renal dysfunction ( Group A ) or patients with normal serum creatinine less than 0.12 mmol/l ( Group B ) did not differ in serum creatinine , creatinine clearance , urinary protein excretion , or quantitative urinary red cell counts . Compliance with EPA therapy was excellent as assessed by plasma fatty acid profiles . At the end of the trial creatinine clearance in treated patients had gone from 80 + /- 16 to 57 + /- 17 ml/min ( p less than 0.05 ) and in untreated patients from 76 + /- 18 to 55 + /- 14 ( p less than 0.05 ) . There were no beneficial effects in either Group A or Group B patients . The only two patients who had improvement in renal function were in the EPA treatment group . Although no side effects of treatment were noted , EPA does not alter the course of established mesangial IgA nephropathy Angiotensin converting-enzyme inhibition ( ACEI ) is a widely accepted treatment during established renal diseases and beneficial effects have also been reported in IgA nephropathy ( IgAN ) . Immunosuppression with myco-phenolate mofetil ( MMF ) has recently been introduced in the treatment of immune-mediated renal diseases showing promising results . Preliminary clinical reports are also suggestive that MMF is effective in severe forms of IgAN . We propose a r and omised prospect i ve trial aim ed to compare long-term renal survival of early IgAN in the course of ACEI therapy with or without MMF immunosuppression Tested was the hypothesis that high-dose omega (omega)-3 fatty acids will be more effective than low-dose omega-3 fatty acids in preserving renal function in patients with severe IgA nephropathy in a r and omized , open-label , parallel-group clinical trial . Patients were assigned to receive either high-dose fatty acids ( EPA 3.76 g and DHA 2.94 g ) or low-dose fatty acids ( EPA 1.88 g and DHA 1.47 g ) , both given daily in a highly purified ethyl ester concentrate ( Omacor ) . Patients were treated for a minimum of 2 yr in the absence of a treatment failure or until study closure ( January 2000 ) . Seventy-three patients were enrolled in the trial with two ranges of elevated serum creatinine ( SC ) : 63 patients ( 86 % ) with a range of 1.5 to 2.9 mg/dl and 10 patients ( 14 % ) with a range of 3.0 to 4.9 mg/dl . The primary end point , within-patient rates of change in SC ( 2-yr minimum ) , showed an annualized median increase in SC of 0.08 mg/dl per yr in the low-dose group and 0.10 mg/dl per yr in the high-dose group ( P : = 0.51 ) . Patients in the lower entry SC range had lower SC slopes ( P : = 0.02 ) and less end-stage renal disease ( ESRD ) ( P : < 0.001 ) compared with those in the higher entry SC range . No patient died , and 18 patients developed ESRD : 10 in the low-dose group and 8 in the high-dose group ( P : = 0.56 ) . SC slopes were significantly lower , and survival free of ESRD was significantly higher ( both , P : = 0.04 ) in the 63 Omacor-treated patients compared with the 22 placebo-treated patients from our previously reported clinical trial in which both groups had a similar level of renal impairment . Patient compliance was excellent , and no serious adverse events were noted . Low-dose and high-dose omega-3 fatty acids were similar in slowing the rate of renal function loss in high-risk patients with IgA nephropathy , particularly those with moderately advanced disease Mycophenolate mofetil ( MMF ) , a new immunosuppressant that selectively inhibits proliferation of T and B lymphocytes , may reduce the frequency and severity of acute graft rejection . Acute graft rejection is the leading cause of graft loss in cadaveric renal transplantation . The purpose of this r and omized , double-blind , multicenter study was to evaluate the efficacy and safety of MMF for the prevention of acute rejection episodes in adult patients during the first 6 months after renal transplantation . A total of 499 patients who were to receive a primary cadaveric renal allograft as their first transplant were r and omized to receive MMF 1.0 g b.i.d . ( MMF 2 g treatment group ) , MMF 1.5 g b.i.d . ( MMF 3 g treatment group ) , or azathioprine 1 - 2 mg/kg/day . CsA , corticosteroids , and antithymocyte globulin ( ATGAM ) were administered as part of a quadruple sequential induction protocol . The primary efficacy endpoint was biopsy-proven rejection or treatment failure ( defined as graft loss , death , or premature withdrawal from the study for any reason ) during the first 6 months after transplant . All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat . The 495 patients who received study drug were included in the safety and secondary efficacy analyses . Biopsy-proven acute rejection episodes or treatment failure occurred in 47.6 % of patients in the azathioprine group compared with 31.1 % ( P = 0.0015 ) and 31.3 % ( P = 0.0021 ) of patients in the MMF 2 g and 3 g treatment groups , respectively . Time to first biopsy-proven rejection episode or treatment failure was significantly longer for MMF 2 g versus azathioprine ( P = 0.0036 ) and MMF 3 g versus azathioprine ( P = 0.0006 ) . First biopsy-proven rejection alone occurred in 38.0 % of patients who received azathioprine compared with 19.8 % and 17.5 % of patients who received MMF 2 g and 3 g , respectively . Patients in the azathioprine group received a greater number of full courses of antirejection treatment as compared with the MMF 2 g and MMF 3 g groups ( 44.5 % , 24.8 % , and 21.1 % , respectively ) . The use of antilymphocyte agents to treat rejection was greater in the azathioprine group ( 20.1 % ) compared with the MMF 2 g group ( 10.3 % ) and the MMF 3 g group ( 5.4 % ) . At 6 months after transplant , graft and patient survival were similar in all 3 treatment groups . ( ABSTRACT TRUNCATED AT 400 WORDS We tested the hypothesis that the combination of converting enzyme inhibitor ( CEI ) with losartan ( LOS ) produces a more profound antiproteinuric effect than either drug alone in normotensive patients with immunoglobulin A ( IgA ) nephropathy . Eight normotensive ( mean blood pressure , 88.9 + /- 2.1 mm Hg ) patients with biopsy-proven IgA nephropathy , nonnephrotic proteinuria ( protein , 1 to 3 g/d ) , and normal or slightly reduced creatinine clearance ( range , 69 to 119 mL/min ) were studied . Clinical evaluations and laboratory tests were performed ( 1 ) before CEI treatment ( basal ) and after ( 2 ) CEI alone ( CEI , 12 weeks ) ; ( 3 ) the combination of CEI and LOS , the latter at a dosage of 50 mg/d ( CEI + LOS , 4 weeks ) ; ( 4 ) LOS alone ( LOS ; 50 mg/d ; 12 weeks ) ; ( 5 ) the combination of LOS and CEI ( LOS + CEI , 4 weeks , at the same dosage as CEI + LOS ) ; and ( 6 ) a doubled dose of either CEI alone or LOS alone for 4 weeks . CEI and LOS as monotherapy significantly reduced proteinuria by 38 % and 30 % , respectively . No further reduction of proteinuria was achieved by doubling the dose of CEI or LOS . Both combinations induced a more remarkable reduction of proteinuria ( 73 % ; P < 0.05 v other periods ) than either drug administered alone . The antiproteinuric effect of CEI or LOS and the more remarkable effect achieved with both combinations was not dependent on the reduction of blood pressure and /or creatinine clearance . In conclusion , this study provides first-time evidence that the combination of CEI and LOS in normotensive patients with IgA nephropathy produces a more profound decrease in proteinuria than either drug . This additive antiproteinuric effect is not dependent on changes in systemic blood pressure and creatinine clearance . Nevertheless , a larger controlled study is required to confirm this novel observation |
2,391 | 16,180,374 | Despite the large variability of included studies , this review reveals a trend in favour of rigid and semi-rigid dressings for achieving stump healing and reduction of stump volume .
No conclusions can be drawn with regard to the effect on functional outcome .
The literature is not conclusive on the effects of early weight bearing on stump healing , volume reduction , and functional outcome . | In order to achieve stump healing after trans-tibial amputation , various methods are applied , such as soft dressings followed by elastic wrapping of the stump , rigid dressings , semi-rigid dressings , and more recently the application of silicon or gel-liners . | OBJECTIVE To assess the effect of a plaster cast socket on the healing of open wounds and on temporary prosthesis fitting after below-knee amputation because of arterial occlusive disease . DESIGN R and omized controlled trial . SETTING Rehabilitation center , university hospital . PATIENTS All included patients had undergone recent ( in the previous 3 months ) below-knee amputation because of arterial disease and initially had an open stump . Patients were r and omly assigned to two groups of 28 subjects each . The sizes of the amputation scars were 8 to 24 cm2 . Ischemia of the stump was eliminated as a probable cause of delayed wound healing by the inclusion criterion of transcutaneous oxygen tension ( TcPO2 ) of > 35 mmHg . The average age in group I ( the experimental group ) was 65.2 + /- 12.4 ( SD ) years and in group II ( the control group ) 66.8 + /- 10.8 years ( not significant ) . INTERVENTION A plaster cast ( supracondylar-type ) socket was fitted on the stumps of group I patients , interposed with a silicone sleeve . The patients were gradually trained to wear this cast for up to 5 hours a day . They were provided with elastic compression b and ages for the remainder of the time . Patients in group II wore elastic compression b and ages , which were only removed for dressing changes . MAIN OUTCOME MEASURES Time required for stump healing , length of time between amputation and ability to walk wearing a contact socket , and length of hospital stay . RESULTS Group I had a quicker average healing time ( 71.2 + /- 31.7 [ SD ] days compared to the control group 's 96.8 + /- 54.9 days ) and a shorter average length of hospital stay ( 99.8 + /- 22.4 days compared to the control group 's 129.9 + /- 48.3 days ) . CONCLUSION Use of a plaster cast socket leads to more rapid healing of the open stump and to a shorter hospitalization . If there is no stump ischemia , this plaster cast technique is safe To evaluate the use of an immediate postoperative prosthesis ( IPOP ) for transtibial amputees , we compared patient outcomes from a prospect i ve clinical study of 19 patients managed with an IPOP with those of a retrospective review of a matched historic control group of 23 patients managed with st and ard soft dressings . Data were analyzed with the Student 's t-test , and significance was set at P=0.05 . The IPOP patients had no surgical revisions , whereas the patients with st and ard soft dressings had 11 . This was a significant difference . IPOP patients also had significantly fewer postoperative complications and shorter times to custom prosthesis than did controls The purpose of this study was to determine if the removable rigid dressing is more effective in preprosthetic management than the conventional support dressing with elastic b and ages . Residual limb circumference , independent application of the dressing , tendency of the dressing to remain secure , development of pressure areas , and presence of pain were evaluated in two groups of below-knee amputees . Subjects were r and omly assigned to use either removable rigid dressings or conventional elastic b and ages . Residual limb circumference was measured three times a week , and the other variables were measured weekly . The results indicated that the removable rigid dressing is more effective in preprosthetic management than the elastic b and age A study of 182 diabetic , largely geriatric , amputees has been presented to compare three different methods of postoperative care . In r and om selected groups , a st and ard soft dressing was compared with a rigid plaster dressing and both were then compared with plaster rigid dressing with an ambulatory pylon attached . The patient population was relatively homogeneous in that they all bore the diagnosis of diabetes . When rigid dressings were applied , they were provided by prosthetists trained specifically for this method of care . The results of this study support the view that the rigid dressing and ambulation do not deter wound healing and probably are a positive factor in achieving a healed wound and a physical and mental attitude able to accept the prosthetic use . However , additional evidence supports the idea that immediate ambulation may be an early deterrent factor to healing and should be delayed for several weeks . The rate of prosthetic use in this study has been greatly improved when compared with previous experience with essentially the same type of patient population ten years ago . Two major reasons for this improvement are the more frequent use of the below-the-knee amputation and the early use of temporary , total-contact prosthetic devices In order to reduce the need for repeated changes of socket due to postoperative atrophy and resorption of oedema simple temporary limbs are required to delay the casting of individual sockets until the stump is more mature . A r and omized study of 95 below-knee amputees was performed with a re-usable temporary one-size prosthesis of endoskeletal type with adjustable tube length . Total contact was obtained by moulding a thin plastic pillow containing small plastic pellets around the stump in parallel connected sections . As air was evacuated the pillow became rigid . The pillow was kept in place about the stump by Velcro b and s. Physiotherapists were able to make all adjustments and ambulate the patient 1–2 hours a day . The training started 2–4 weeks after amputation and lasted for 1–4 weeks . Healing problems due to training did not occur in well healed stumps where training started 3 weeks or more after amputation . No negative influence on maturing of stump , hospital stay and walking ability three months after amputation was found The most popular early walking aid ( EWA ) in the United Kingdom ( UK ) is the Pneumatic PostAmputation Mobility aid or PPAM aid . A disadvantage of this device is that it does not allow a transtibial amputee to flex or extend the knee during walking . The Amputee Mobility Aid ( AMA ) was developed to allow knee movement , enabling transtibial amputees to practise a more natural gait . The benefits of using EWAs include early walking , reduction in postoperative oedema and improvement in patient morale . This pilot study investigated the pneumatic bag/stump interface pressures of the PPAM aid and the AMA . In addition , the range of motion of the knee on the amputated side and the mechanical knee of the AMA were compared . The AMA was found to have higher interface pressures than the PPAM aid during st and ing and similar pressures during supported walking . Subjects using the AMA did flex and extend their knee during walking but through a reduced range of motion . There were no significant differences between the angular movements of the AMA 's mechanical knee and the patient 's knee within it OBJECTIVES To compare the functional outcome associated with the use of Unna semirigid dressings ( SRD ) and elastic b and age soft dressings ( ED ) for adults with lower limb amputation . DESIGN Experimental design . SETTING Inpatient rehabilitation unit of an urban academic medical center . PARTICIPANTS A successive series of adults with vascular disease who had lower limb amputation surgery . Subjects were r and omly assigned to the SRD ( 12 patients with 12 recent amputations ) or the ED ( 9 patients with 10 recent amputations ) group . Subjects in each group were not significantly different except for age ; those in the SRD group were somewhat older . INTERVENTION Subjects in the SRD group had Unna dressings applied to the amputation limb by physical therapists trained in the technique . Those in the ED group had elastic b and aging by therapists , nurses , family , and themselves , all of whom were trained in the technique . RESULTS Sixty-seven percent of the SRD group and 20 % of those in the ED group were discharged from the rehabilitation unit ambulating with prostheses . Of those who received prostheses , time from admission to the rehabilitation unit to readiness for fitting averaged 20.8 days for the SRD group and 28.7 days for the ED group . Comparison of survival curves shows that the time from surgery to fitting in the SRD group was almost half that of the ED group ; 30 % of the SRD group was fitted within 34 days , whereas it took 64 days for the same percentage of the ED group to be fitted . CONCLUSIONS Unna semirigid dressings are more effective in fostering amputation limb wound healing and preparing the amputation limb for prosthetic fitting . Subjects treated with SRDs were more likely to be fitted with prostheses and to return home walking with a prosthesis To evaluate the effect of wound dressing upon wound healing , fifty-one patients undergoing below-knee amputation using a long posterior myocutaneous flap technic were r and omly allocated into a soft or plaster dressing group . Neither wound dressing technic proved superior , as wounds healed in 85.2 per cent of the plaster dressing group and 83.3 per cent of the soft dressing group |
2,392 | 27,009,521 | Interventions that combine pharmacotherapy and behavioural support increase smoking cessation success compared to a minimal intervention or usual care .
Although trials differed in the details of their population s and interventions , we did not detect any factors that modified treatment effects apart from the recruitment setting .
We did not find evidence from indirect comparisons that offering more intensive behavioural support was associated with larger treatment effects | BACKGROUND Both behavioural support ( including brief advice and counselling ) and pharmacotherapies ( including nicotine replacement therapy ( NRT ) , varenicline and bupropion ) are effective in helping people to stop smoking .
Combining both treatment approaches is recommended where possible , but the size of the treatment effect with different combinations and in different setting s and population s is unclear .
OBJECTIVES To assess the effect of combining behavioural support and medication to aid smoking cessation , compared to a minimal intervention or usual care , and to identify whether there are different effects depending on characteristics of the treatment setting , intervention , population treated , or take-up of treatment . | Tobacco use is the single most important preventable cause of death in military personnel . The purpose of this r and omized clinical trial was to evaluate the effectiveness of two behavioral interventions when added to nicotine-replacement therapy on smoking cessation . The sample of 512 included 52 % active duty military , 29 % family , 11 % retirees , and 8 % Department of Defense civilians . There was a main effect of compliance at the end of the program ( EOP ) ; 69 % of those who attended 75 % of the classes were abstinent from tobacco ; regression analysis found the more intensive program to be twice as effective at EOP and at 3 months , an outcome not continued at 6 months . The longer , more intensive V and erbilt University Medical Center program was significantly more effective at helping the civilian portion of the population ( 85 % versus 60 % in the American Cancer Society program ) but not the active duty participants Residential treatment for substance use disorders ( SUD ) provides opportunity for smoking intervention . A r and omized controlled trial compared : ( 1 ) motivational interviewing ( MI ) to brief advice ( BA ) , ( 2 ) in one session or with two booster sessions , for 165 alcoholics in SUD treatment . All received nicotine replacement ( NRT ) . MI and BA produced equivalent confirmed abstinence , averaging 10 % at 1 month , and 2 % at 3 , 6 and 12 months . However , patients with more drug use pretreatment ( > 22 days in 6 months ) given BA had more abstinence at 12 months ( 7 % ) than patients in MI or with less drug use ( all 0 % ) . Boosters produced 16 - 31 % fewer cigarettes per day after BA than MI . Substance use was unaffected by treatment condition or smoking cessation . Motivation to quit was higher after BA than MI . Thus , BA plus NRT may be a cost-effective way to reduce smoking for alcoholics with comorbid substance use who are not seeking smoking cessation Background There is no more effective intervention for secondary prevention of coronary heart disease than smoking cessation . Yet , evidence about the (cost-)effectiveness of smoking cessation treatment methods for cardiac in patients that also suit nursing practice is scarce . This protocol describes the design of a study on the (cost-)effectiveness of two intensive smoking cessation interventions for hospitalised cardiac patients as well as first results on the inclusion rates and the characteristics of the study population . Methods / design An experimental study design is used in eight cardiac wards of hospitals throughout the Netherl and s to assess the (cost-)effectiveness of two intensive smoking cessation counselling methods both combined with nicotine replacement therapy . R and omization is conducted at the ward level ( cross-over ) . Baseline and follow-up measurements after six and 12 months are obtained . Upon admission to the cardiac ward , nurses assess patients ’ smoking behaviour , ensure a quit advice and subsequently refer patients for either telephone counselling or face-to-face counselling . The counselling interventions have a comparable structure and content but differ in provider and delivery method , and in duration . Both counselling interventions are compared with a control group receiving no additional treatment beyond the usual care . Between December 2009 and June 2011 , 245 cardiac patients who smoked prior to hospitalisation were included in the usual care group , 223 in the telephone counselling group and 157 in the face-to-face counselling group . Patients are predominantly male and have a mean age of 57 years . Acute coronary syndrome is the most frequently reported admission diagnosis . The ultimate goal of the study is to assess the effects of the interventions on smoking abstinence and their cost-effectiveness . Telephone counselling is expected to be more (cost-)effective in highly motivated patients and patients with high SES , whereas face-to-face counselling is expected to be more (cost-)effective in less motivated patients and patients with low SES . Discussion This study examines two intensive smoking cessation interventions for cardiac patients using a multi-centre trial with eight cardiac wards . Although not all eligible patients could be included and the distribution of patients is skewed in the different groups , the results will be able to provide valuable insight into effects and costs of counselling interventions varying in delivery mode and intensity , also concerning subgroups . Trial registration Dutch Trial Register 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 PURPOSE / OBJECTIVES To determine the predictors of participation in a smoking-cessation program among patients with head and neck cancer . DESIGN This cross-sectional study is a sub study of a larger , r and omized trial of patients with head and neck cancer that determined the predictors of smokers ' participation in a cessation intervention . SETTING Otolaryngology clinics at three Veterans Affairs medical centers ( Ann Arbor , MI , Gainesville , FL , and Dallas , TX ) , and the University of Michigan Hospital in Ann Arbor . SAMPLE 286 patients who had smoked within six months of the screening survey were eligible for a smoking-cessation intervention . METHODS Descriptive statistics and bivariate and multivariate logistic regression were used to determine the independent predictors of smokers ' participation in an intervention study . MAIN RESEARCH VARIABLES Perceived difficulty quitting ( as a construct of self-efficacy ) , health behaviors ( i.e. , smoking and problem drinking ) , clinical characteristics ( i.e. , depression and cancer site and stage ) , and demographic variables . FINDINGS Forty-eight percent of those eligible participated . High perceived difficulty quitting was the only statistically significant predictor of participation , whereas problem drinking , lower depressive symptoms , and laryngeal cancer site approached significance . CONCLUSIONS Special outreach may be needed to reach patients with head and neck cancer who are overly confident in quitting , problem drinkers , and patients with laryngeal cancer . IMPLICATION S FOR NURSING Oncology nurses are in an opportune position to assess patients ' perceived difficulty quitting smoking and motivate them to enroll in cessation programs , ultimately improving quality of life , reducing risk of recurrence , and increasing survival for this population OBJECTIVES To investigate the effects on serum lipids , plasma fibrinogen , plasma insulin , plasma C-peptide and blood glucose , of smoking cessation after 4 months . To develop a group-based smoking intervention programme in primary health care . SETTING Twenty health centres in primary health care in southern Sweden . SUBJECTS Four hundred habitual smokers ( > 10 cigarettes per day-1 , > 10 years ) , recruited by advertisement in local papers . INTERVENTION The smokers were r and omized , after stratification for age and sex , to one intervention group ( n = 200 ) and one control group ( n = 200 ) . The intervention group was offered supportive group sessions and free nicotine supplementation ( patches , chewing gum ) . MAIN OUTCOME MEASURES All participants were investigated at the start and after 4 months ( medical history , physical examination , laboratory evaluation ) . Blood sample s were drawn for determination of glucose , insulin and C-peptide , both in the fasting state and during an oral glucose tolerance test ( OGTT ) , and for measurement of lipoproteins , fibrinogen , nicotine and cotinine . RESULTS In the intervention group 98 of the subjects ( 48 % ) had quit smoking after 4 months . They were compared with the 156 subjects in the control group ( 91 % ) who were still daily smokers during the whole period . There were no significant differences in any variable between the two ( total ) experimental groups at baseline . Plasma nicotine and cotinine decreased ( P < 0.001 ) in the intervention group following smoking cessation , and weight increased by 2.7 kg . In the intervention group HDL-cholesterol increased by 11 % ( P < 0.001 ) , whereas HbA1c increased by 2 % ( P < 0.05 ) only in the control group . No changes occurred in levels of glucose , insulin , C-peptide and fibrinogen . CONCLUSION The smoking cessation programme had a success rate of almost 50 % over 4 months . Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance . A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism Tobacco Dependence among smokers with psychiatric disorders has been under-addressed by the mental health , addictions , and tobacco control communities . This study examined depressed smokers ' readiness to quit and the applicability of the Stages of Change framework to a psychiatric sample . Currently depressed smokers ( N=322 ) were recruited from four outpatient psychiatric clinics . Participants averaged 16 cigarettes per day ( S.D.=10 ) and 24 years ( S.D.=13 ) of smoking . The majority ( 79 % ) reported intention to quit smoking with 24 % ready to take action in the next 30 days . Individuals in the preparation stage reported more prior quit attempts , a greater commitment to abstinence , increased recognition of the cons of smoking , and greater use of the processes of change . Precontemplators were least likely to identify a goal related to their smoking behavior . Depressive symptom severity and history of recurrent depressive episodes were unrelated to readiness to quit . This study is one of the first to examine the smoking behaviors of currently depressed psychiatric out patients . The level and longevity of their tobacco use underscore the need for cessation interventions . The consistency in hypothesized patterns among theoretical constructs of the Stages of Change model supports the transfer of stage-tailored interventions to this clinical population Smoking exerts detrimental effects on dental treatment and oral health . Our goal was to evaluate effectiveness in terms of the abstinence rate in smoking-cessation intervention delivered by dental professionals . Individuals who were willing to quit smoking were r and omly assigned to either an intervention or a non-intervention group . Intensive intervention was provided , consisting of 5 counseling sessions , including an additional nicotine replacement regimen . Reported abstinence was verified by the salivary cotinine level . Thirty-three persons in the intervention and 23 in the non-intervention group started the trial . On an intent-to-treat basis , 3- , 6- and 12-month continuous abstinence rates in the intervention group were 51.5 % , 39.4 % , and 36.4 % , respectively , while the rates in the non-intervention group were consistent at 13.0 % . Adjusted odds ratios ( 95 % confidence interval ) by logistic stepwise regression analyses were 7.1 ( 1.8 , 28.5 ) , 8.9 ( 1.7 , 47.2 ) , and 6.4 ( 1.3 , 30.7 ) , respectively . Intensive smoking-cessation intervention in the dental setting was therefore effective INTRODUCTION Identifying successful smoking treatment interventions and methods of delivery is critical given the smoking rates among HIV-positive population s and the medical implication s of smoking in this population . This study compared the efficacy of 3 smoking cessation interventions provided in HIV clinical treatment setting s. METHODS Following a baseline assessment , 209 HIV-positive smokers were r and omly assigned to 1 of 3 conditions in a parallel group design . Treatment conditions were individual counseling plus nicotine replacement treatment ( NRT ) , a computer-based Internet smoking treatment plus NRT , and self-help plus NRT . Smoking status was determined at follow-up assessment s completed at 12 , 24 , 36 , and 52 weeks following treatment initiation . RESULTS Cessation rates ranged from 15 % to 29 % ; however , no statistically significant differences in abstinence were found among the treatment conditions over time . Those employed , those who reported a greater desire to quit , or those with lower mood disturbance scores were more likely to achieve abstinence ( p < .01 ) . The number of cigarettes participants reported smoking in the 24hr prior to each assessment significantly declined over time ( p < .001 ) . CONCLUSIONS Although we found no differences in abstinence rates across groups , the results indicate that integration of smoking cessation interventions is feasible in HIV clinical treatment setting s , and cessation results are promising . The overall abstinence rates we report are comparable to those found in similar treatment studies across multiple population s. Further research is warranted Background Tobacco use continues to be a global public health problem . Helping patients to quit is part of the preventive role of all health professionals . There is now increasing interest in the role that the dental team can play in helping their patients to quit smoking . The aim of this study was to determine the feasibility of undertaking a r and omised controlled smoking cessation intervention , utilising dental hygienists to deliver tobacco cessation advice to a cohort of periodontal patients . Methods One hundred and eighteen patients who attended consultant clinics in an outpatient dental hospital department ( Periodontology ) were recruited into a trial . Data were available for 116 participants , 59 intervention and 57 control , and were analysed on an intention-to-treat basis . The intervention group received smoking cessation advice based on the 5As ( ask , advise , assess , assist , arrange follow-up ) and were offered nicotine replacement therapy ( NRT ) , whereas the control group received ' usual care ' . Outcome measures included self-reported smoking cessation , verified by salivary cotinine measurement and CO measurements . Self-reported measures in those trial participants who did not quit included number and length of quit attempts and reduction in smoking . Results At 3 months , 9/59 ( 15 % ) of the intervention group had quit compared to 5/57 ( 9 % ) of the controls . At 6 months , 6/59 ( 10 % ) of the intervention group quit compared to 3/57 ( 5 % ) of the controls . At one year , there were 4/59 ( 7 % ) intervention quitters , compared to 2/59 ( 4 % ) control quitters . In participants who described themselves as smokers , at 3 and 6 months , a statistically higher percentage of intervention participants reported that they had had a quit attempt of at least one week in the preceding 3 months ( 37 % and 47 % , for the intervention group respectively , compared with 18 % and 16 % for the control group ) . Conclusion This study has shown the potential that trained dental hygienists could have in delivering smoking cessation advice . While success may be modest , public health gain would indicate that the dental team should participate in this activity . However , to add to the knowledge-base , a multi-centred r and omised controlled trial , utilising biochemical verification would be required to be undertaken AIM The study aim ed to test simultaneously our underst and ing of the effects of bupropion sustained-release ( SR ) treatment on putative mediators and our underst and ing of determinants of post-quit abstinence , including withdrawal distress , cigarette craving , positive affect and subjective reactions to cigarettes smoked during a lapse . The specificity of bupropion SR effects was also tested in exploratory analyses . DESIGN Data from a r and omized , placebo-controlled clinical trial of bupropion SR were su bmi tted to mediation analyses . SETTING Center for Tobacco Research and Intervention , Madison , WI , USA . PARTICIPANTS A total of 403 adult , daily smokers without contraindications to bupropion SR use . INTERVENTION Participants were assigned r and omly to receive a 9-week course of bupropion SR or placebo pill and to receive eight brief individual counseling sessions or no counseling . MEASUREMENTS Ecological momentary assessment ratings of smoking behavior and putative mediators were collected pre- and post-quit . FINDINGS Results of structural equation and hierarchical linear models did not support the hypothesis that bupropion SR treatment improves short-term abstinence by reducing withdrawal distress or affecting the subjective effects of a lapse cigarette , but provided partial support for mediation by cigarette craving reduction and enhanced positive affect . Bupropion SR effects on point-prevalence abstinence at 1 month post-quit were also mediated partially by enhanced motivation to quit and self-efficacy . CONCLUSIONS Results provided some support for models of bupropion SR treatment and relapse and suggested that motivational processes may partially account for bupropion SR efficacy Sustained-release bupropion and nortriptyline have been shown to be effcacious in treating cigarette smoking . Psychological intervention is also recognized as efficacious . The cost and cost-effectiveness of the 2 drug therapies have not been estimated . It was hypothesized that nortriptyline would be more cost-effective than bupropion . Hypotheses were not originally proposed concerning the cost-effectiveness of psychological versus drug treatment , but the 2 were compared using exploratory analyses . This was a 3 ( bupropion versus nortriptyline versus placebo ) by 2 ( medical management alone versus medical management plus psychological intervention ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were cost and cost-effectiveness computed at week 52 . Nortriptyline cost less than bupropion . Nortriptyline was more cost-effective than bupropion ; the difference was not statistically significant . Psychological intervention cost less than the 2 drug treatments , and was more cost-effective , but not significantly so . Prospect i ve investigations of the cost and cost-effectiveness of psychological and pharmacological intervention , using adequate sample sizes , are warranted BACKGROUND Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking . It is not known whether psychological intervention increases the efficacy of these antidepressants . This study compared both drugs with placebo . It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention . METHODS This was a 2 ( medical management vs psychological intervention ) x 3 ( bupropion vs nortriptyline vs placebo ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 36 , and 52 . RESULTS Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone . With the use of point-prevalence abstinence , both nortriptyline and bupropion were more efficacious than placebo . On rates of 1-year continuous abstinence , the 2 drugs did not differ from each other or from placebo . Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence . CONCLUSIONS Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers . Similarly , psychological intervention produces better abstinence rates than simple medical management . Both drugs , and psychological intervention , have limited efficacy in producing sustained abstinence . The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone Background : Guidelines recommend that smoking cessation interventions are offered in all clinical setting s to all smokers willing to make a quit attempt . Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy ( NRT ) to smokers admitted to hospital has not been established , a r and omised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital in patients . Methods : Medical and surgical in patients who were current smokers at the time of admission were r and omised to receive either usual care ( no additional advice at admission ) , counselling alone ( 20 minute intervention with written material s ) , or NRT plus counselling ( counselling intervention with a 6 week course of NRT ) . Continuous and point prevalence abstinence from smoking ( vali date d by exhaled carbon monoxide < 10 ppm ) was measured at discharge from hospital and at 3 and 12 months , and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months . Results : 274 inpatient smokers were enrolled . Abstinence was higher in the NRT plus counselling group ( n=91 ) than in the counselling alone ( n=91 ) or usual care ( n=92 ) groups . The difference between the groups was significant for vali date d point prevalence abstinence at discharge ( 55 % , 43 % , 37 % respectively , p=0.045 ) and at 12 months ( 17 % , 6 % , 8 % , p=0.03 ) . The respective differences in continuous vali date d abstinence at 12 months were 11 % , 4 % , 8 % ( p=0.25 ) . There was no significant difference between counselling alone and usual care , or in reduction in cigarette consumption between the treatment groups . Conclusions : NRT given with brief counselling to hospital in patients is an effective routine smoking cessation intervention BACKGROUND This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking . METHODS A total of 214 Medicaid-eligible women smokers of childbearing age were r and omized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months . Assessment s were conducted by telephone at baseline , 10 days , and 3 and 6 months after enrollment . RESULTS At the 3-month follow-up , significantly more women in the patch plus proactive telephone support condition were abstinent ( 42 % ) compared to the patch only condition ( 28 % ) ( P = 0.03 ) . Similarly , more women in the experimental condition were abstinent at both the 10-day and 3-month assessment s ( 32 v 19 % , P = 0.02 ) . However , differences were not found at the 6-month follow-up , suggesting that the addition of proactive telephone peer support enhanced short-term , but not long-term cessation . CONCLUSIONS This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population Background Telephone quit lines are accessible to many smokers and are used to engage motivated smokers to make quit attempts . Smoking cessation counselling provided via telephone can either be reactive ( i.e. primarily involving the provision of evidence -based information ) , or proactive ( i.e. primarily involving repeated , sequenced calls from and interaction with trained cessation counsellors ) . Some studies have found proactive telephone counselling more effective and this trial will investigate whether or not proactive telephone support for smoking cessation , delivered through the National Health Service ( NHS ) Smoking Helpline is more effective or cost-effective than reactive support . It will also investigate whether or not providing nicotine replacement therapy ( NRT ) , in addition to telephone counselling , has an adjunctive impact on smoking cessation rates and whether or not this is cost effective . Methods This will be a parallel group , factorial design RCT , conducted through the English national NHS Smoking Helpline which is run from headquarters in Glasgow . Participants will be smokers who call the helpline from any location in Engl and and who wish to stop smoking . If 644 participants are recruited to four equally-sized trial groups ( total sample size = 2576 ) , the trial will have 90 % power for detecting a treatment effect ( Odds Ratio ) of 1.5 for each of the two interventions : i ) proactive versus reactive support and ii ) the offer of NRT versus no offer . The primary outcome measure for the study is self-reported , prolonged abstinence from smoking for at least six months following an agreed quit date . A concurrent health economic evaluation will investigate the cost effectiveness of the two interventions when delivered via a telephone helpline . Discussion The PORTSSS trial will provide high quality evidence to determine the most appropriate kind of counselling which should be provided via the NHS Smoking Helpline and also whether or not an additional offer of cost-free NRT is effective and cost effective for smoking cessation . Trial Registration ( clinical trials.gov ) : Purpose . This study describes the design , recruitment , and baseline data of the first smoking-cessation clinical trial for African-American light smokers , Kick It at Swope II ( KIS-II ) . Design . KIS-II was a r and omized trial testing the efficacy of nicotine gum ( vs. placebo gum ) in combination with counseling ( motivational interviewing or health education ) . Setting . This study was conducted at an urban community-based clinic serving predominantly lower-income African-Americans . Subjects . African-Americans who smoked 1 to 10 cigarettes per day were eligible . Of 1933 individuals screened , 1012 ( 52 % ) were eligible and 755 ( 75 % ) were enrolled in the study . Measures . Baseline assessment included smoking history and psychometric measures . Analysis . The majority of participants were women ( 67 % ) with a mean age of 45.1 years ( SD = 10.7 ) . Participants smoked on average 7.6 cigarettes ( SD = 3.21 ) per day , had a mean exhaled carbon monoxide level of 13.9 ppm ( SD = 8.9 ) and a mean serum cotinine level of 244.2 ng/mL ( SD = 154.4 ) , and reported high levels of motivation and confidence to quit smoking . Conclusion . African-American light smokers were motivated to stop smoking and to enroll in a smoking-cessation program . Characteristics of our sample suggest African-American light smokers are an appropriate group for inclusion in smoking-cessation interventions Background : Previously , we have linked theoretically based cognitive and emotional variables to the ability of cancer patients to quit smoking . Purpose : In this study , we evaluated the impact of cognitive-behavioral therapy ( CBT ) , which addressed these theoretically derived cognitive and emotional variables linked to tobacco use in this population , for promoting smoking cessation in a sample of cancer patients and assessed longitudinal predictors of smoking cessation . Methods : Cancer patients ( N=109 ) were r and omized to either the theoretically based CBT intervention or to a general health education ( GHE ) condition , and all patients received nicotine replacement therapy . Results : Contrary to our expectation , no significant difference in 30-day point-prevalence abstinence between the CBT and GHE conditions was detected at either a 1-month ( 44.9 % vs. 47.3 % , respectively ) or 3-month ( 43.2 % vs. 39.2 % , respectively ) follow-up evaluation . Higher quit motivation and lower cons of quitting were related to smoking cessation . Conclusions : Implication s for the implementation of smoking cessation behavioral treatments in the oncologic context are discussed , as are directions for future research in this area Purpose The purpose of this study was to evaluate the impact of a tobacco cessation intervention using motivational interviewing on smoking cessation rates during diabetes self-management training ( DSMT ) . Methods A r and omized controlled trial was conducted with subjects recruited from an ongoing type 2 diabetes adult education program at a large diabetes center . A total of 114 subjects were r and omized to intervention ( n = 57 ; face-to-face motivational interviewing plus telephone counseling and offering of medication ) or st and ard care ( n = 57 ) . Outcome measures included tobacco cessation rates , mean number of cigarettes smoked , A1C , weight , blood pressure , and lipids . Results Intensive intervention using motivational interviewing integrated into a st and ard DSMT program result ed in a trend toward greater abstinence at 3 months of follow-up in those receiving the intervention . However , this same trend was not observed at 6 months . The addition of this structured smoking cessation intervention did not negatively affect either diabetes education or other measures of diabetes management , including A1C values Background Smoking rates , and associated negative health outcomes , are disproportionately high among people with mental illness compared to the general population . Smoke-free policies within mental health hospitals can positively impact on patients ’ motivation and self-efficacy to address their smoking . However , without post-discharge support , preadmission smoking behaviours typically resume . This protocol describes a r and omised controlled trial that aims to assess the efficacy of linking mental health in patients to community-based smoking cessation supports upon discharge as a means of reducing smoking prevalence . Methods / Design Eight hundred participants with acute mental illness will be recruited into the r and omised controlled trial whilst in patients at one of four psychiatric inpatient facilities in the state of New South Wales , Australia . After completing a baseline interview , participants will be r and omly allocated to receive either : ‘ Supported Care ’ , a multimodal smoking cessation intervention ; or ‘ Normal Care ’ , consisting of existing hospital care only . The ‘ Supported Care ’ intervention will consist of a brief motivational interview and a package of self-help material for abstaining from smoking whilst in hospital , and , following discharge , 16 weeks of motivational telephone-based counselling , 12 weeks of free nicotine replacement therapy , and a referral to the Quitline . Data will be collected at 1 , 6 and 12 months post-discharge via computer-assisted telephone interview . The primary outcomes are abstinence from smoking ( 7-day point prevalence and prolonged cessation ) , and secondary outcomes comprise daily cigarette consumption , nicotine dependence , quit attempts , and readiness to change smoking behaviour . Discussion If shown to be effective , the study will provide evidence in support of systemic changes in the provision of smoking cessation care to patients following discharge from psychiatric inpatient facilities . Trial registration Australian New Zeal and Clinical Trials Registry ANZTCN : ACTRN12612001042831 . Date registered : 28 September 2012 This study is a r and omized , double-blind , placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment ( CBTD ) and of bupropion , both singularly and in combination , on smoking cessation in adult smokers . As an extension of our previous work , we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors . Participants were 524 smokers ( 47.5 % female , M ( age ) = 44.27 years ) who were r and omized to one of four 12-week treatments : ( a ) st and ard , cognitive-behavioral smoking cessation treatment ( ST ) plus bupropion ( BUP ) , ( b ) ST plus placebo ( PLAC ) , ( c ) st and ard cessation treatment combined with cognitive-behavioral treatment for depression ( CBTD ) plus BUP , and ( d ) CBTD plus PLAC . Follow-up assessment s were conducted 2 , 6 , and 12 months after treatment , and self-reported abstinence was verified biochemically . Consistent with previous studies , bupropion , in comparison with placebo , result ed in better smoking outcomes in both intensive group treatments . Adding CBTD to st and ard intensive group treatment did not result in improved smoking cessation outcomes . In addition , neither CBTD nor bupropion , either alone or in combination , was differentially effective for smokers with single-past-episode major depressive disorder ( MDD ) , recurrent MDD , or elevated depressive symptoms . However , findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample . An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials Background Mental health in patients smoke at higher rates than the general population and are disproportionately affected by tobacco dependence . Despite the advent of smoke free policies within mental health hospitals , limited systems are in place to support a cessation attempt post hospitalisation , and international evidence suggests that most smokers return to pre-admission smoking levels following discharge . This protocol describes a r and omised controlled trial that will test the feasibility , acceptability and efficacy of linking inpatient smoking care with ongoing community cessation support for smokers with a mental illness . Methods / Design This study will be conducted as a r and omised controlled trial . 200 smokers with an acute mental illness will be recruited from a large inpatient mental health facility . Participants will complete a baseline survey and will be r and omised to either a multimodal smoking cessation intervention or provided with hospital smoking care only . R and omisation will be stratified by diagnosis ( psychotic , non-psychotic ) . Intervention participants will be provided with a brief motivational interview in the inpatient setting and options of ongoing smoking cessation support post discharge : nicotine replacement therapy ( NRT ) ; referral to Quitline ; smoking cessation groups ; and fortnightly telephone support . Outcome data , including cigarettes smoked per day , quit attempts , and self-reported 7-day point prevalence abstinence ( vali date d by exhaled carbon monoxide ) , will be collected via blind interview at one week , two months , four months and six months post discharge . Process information will also be collected , including the use of cessation supports and cost of the intervention . Discussion This study will provide comprehensive data on the potential of an integrated , multimodal smoking cessation intervention for persons with an acute mental illness , linking inpatient with community cessation support . Trial Registration Australian and New Zeal and Clinical Trials Registry ANZTCN : This prospect i ve study examined the effect of three behavioral smoking interventions and reductions in cigarettes smoked per day on nicotine withdrawal symptoms in 141 abstinent alcoholic smokers ( 73 men , 68 women ) . The participants ' mean + /- SD age was 41.4 + /- 9.2 years . They smoked an average of 27.7 + /- 12.1 cigarettes per day and reported 4.1 + /- 4.3 years of current abstinent from alcohol and other drugs of dependence . Participants were r and omly assigned to a 12-week program of st and ard treatment ( ST , n = 61 ) , behavioral counseling plus exercise ( BEX , n = 39 ) , or behavioral counseling plus nicotine gum ( BNIC , n = 41 ) . All three conditions included instructions to reduce the number of cigarettes smoked per day prior to the target quit date ( TQD ) . The TQD was week 4 for ST subjects and week 8 for those in the BEX and BNIC groups . The post-treatment assessment occurred one week after TQD . The Profile of Mood States ( POMS ) and the Beck Depression Inventory were administered at baseline and posttreatment to assess nicotine withdrawal . Significant increases were detected for the POMS total mood disturbance score , and the depression , tension , anger and confusion subscales , while vigor scores decreased ( all p < 0.03 ) . Withdrawal change scores were not found to be associated with treatment condition or percentage reduction in cigarettes , and there was no evidence of a significant interaction of treatment and cigarette reduction . Results are discussed in relation to implication s for treatment and for future research BACKGROUND The design and results of the initial intervention program of the Lung Health Study are presented for 3,923 male and female participants . One of the major aims of this clinical trial was to achieve smoking cessation early in the study and to provide intensive follow-up procedures for maintaining abstinence . In addition , compliance with use of aerosolized inhalers ( either placebo or active bronchodilator ) would be necessary in order to achieve the trial goal of improved pulmonary function . RESULTS Eighty-eight percent of the special intervention participants attended the 4-month follow-up visit . Forty-six percent reported not smoking from quit day through the visit , and an additional 13 % had stopped smoking at the end of 4 months , although they had not achieved abstinence since quit day . The aerosol inhaler compliance was self-reported at 81 % at the 4-month visit . Validating the self-reports by weighing canisters reduced the " good " compliance rates to 66 % . CONCLUSIONS The intensive behavioral program was effective in achieving high initial rates of smoking cessation and inhaler compliance . Use of nicotine gum appeared to be an effective adjunct to the multicomponent behavioral program . Smoking status does appear to be related to inhaler compliance among both men and women participants This article describes the test of the hypothesis that a cognitive-behavioral mood management intervention would be effective for smokers with a history of major depressive disorder ( MDD ) . The method was r and omized trial ; the assessment s occurred at Weeks 0 , 8 , 12 , 26 , and 52 . Ss were 149 smokers ; 31 % had a history of MDD . All received 2 mg of nicotine gum . Mood management was provided in 10 group sessions over 8 weeks . St and ard treatment was provided in 5 group sessions over 8 weeks . Outcome was continuous abstinence . History-positive Ss were more likely to be abstinent when treated with mood management . Treatment condition differences were not significant for history-negative Ss . For history-positive Ss , less anger at baseline predicted abstinence . For history-negative Ss , more years smoked and higher baseline carbon monoxide ( CO ) predicted abstinence . Cognitive-behavioral therapy did not affect mood after quitting . Abstinence predictors differed as a function of baseline diagnosis We conducted a r and omized , controlled study to evaluate whether pharmacists ' advice on smoking cessation would result in a higher smoking cessation rate using Nicorette ( nicotine gum preparation ) . Fourteen pharmacies in Tokyo , Kanagawa , and Nagano participated . Smokers who visited pharmacies to buy Nicorette from March 1 , 2002 , through August 31 , 2002 , were recruited and r and omly assigned to two groups . For the intervention group ( A ) , pharmacists provided both regular instructions on Nicorette use and smoking cessation advice at the first sale and then gave follow-up advice just before starting a cessation and 1 , 3 , and 8 weeks and 3 months thereafter . For the control group ( B ) , pharmacists provided regular instructions alone . The primary outcome measure was the self-reported smoking cessation rate and the secondary outcome measure was the relationship between the smoker 's egogram and effectiveness of intervention . Twenty-eight smokers were enrolled and r and omized into group A ( n=11 ) or group B ( n=17 ) . The absolute abstinence rate in groups A and B at 3 months was 45.5 % and 31.2 % , respectively . The odds ratio was 1.83 , which was not statistically significant . There was no difference in egogram score between absolute abstinence subjects and nonabstinence subjects in group A. The egogram scores in Adapted Child of absolute abstinence subjects in group B were significantly higher than in nonabstinence subjects . In conclusion , instructions and advice given by pharmacists may improve the smoking cessation rate in smokers receiving nicotine replacement therapy We analyzed data from a r and omized trial of 322 actively depressed smokers and examined the effect of smoking cessation on their mental health functioning . Only 1 of 10 measures at 4 follow-up time points was significant : participants who successfully stopped smoking reported less alcohol use than did participants who continued smoking . Depressive symptoms declined significantly over time for participants who stopped smoking and those who continued smoking ; there were no group differences . Individuals in treatment for clinical depression can be helped to stop smoking without adversely affecting their mental health functioning The A1 allele of the dopamine D2 receptor gene ( DRD2 ) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior . In a study of smokers enrolled in an open-label , r and omized effectiveness trial , we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling . Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months , respectively , following a target quit date . Compared to women who carry both A2 alleles , women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects ( odds ratio (OR)=1.91 , 95 % confidence interval (CI)=1.01–3.60 ; P<0.04 ) and at 12 months were somewhat more likely to report smoking ( OR=0.76 , 95 % CI=0.56–1.03 ; P<0.076 ) . Significant associations or trends were not observed in men . In women , individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function INTRODUCTION To determine the cost-effectiveness of a high-intensity smoking cessation program ( SmokeStop Therapy ; SST ) versus a medium-intensity treatment ( Minimal Intervention Strategy for Lung patients [ LMIS ] ) for chronic obstructive pulmonary disease out patients . METHODS The cost-effectiveness analysis was based on a r and omized controlled trial investigating the effectiveness of the SST compared with the LMIS with 12-month follow-up . The primary outcome measure was the cotinine-vali date d continuous abstinence rate based on intention to treat . A health care perspective was adopted , with outcomes assessed in terms of ( incremental ) additional quitters gained , exacerbations prevented , and hospital days prevented . Health care re source use , associated with smoking cessation , was collected at baseline and 12 months after the start of the interventions . Monte Carlo simulations were performed to evaluate the robustness of the results . RESULTS The average patient receiving SST generated € 581 in health care costs , including the costs of the smoking cessation program , versus € 595 in the LMIS . The SST is also associated with a lower average number of exacerbations ( 0.38 vs. 0.60 ) and hospital days ( 0.39 vs. 1 ) per patient and a higher number of quitters ( 20 vs. 9 ) at lower total costs . This leads to a dominance of the SST compared with the LMIS . CONCLUSIONS The high-intensive SST is more cost-effective than the medium-intensive LMIS after 1 year . This is associated with cost savings per additional quitter , prevented exacerbations , and hospital days at lower or equal costs 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 Objectives : The purpose of this study was to evaluate a nurse-managed , lay-led tobacco cessation intervention delivered to adult women in Ohio Appalachia . Methods : A r and omized controlled experimental design included intervention participants ( n = 147 ) enrolled in a nurse-managed , lay-led protocol that incorporated nicotine replacement and behavioral counseling . Control participants ( n = 155 ) received a personalized letter from their clinic physician , who advised them to quit smoking and requested they schedule a clinic appointment to discuss cessation . Results : Self-reported and cotinine-vali date d quit rates were significantly higher among intervention group participants compared with control group participants at 3- and 6-month follow-up ( P < 0.02 ) . At 12 months , self-reported abstinence was 19.1 % ( intervention group ) and 9.0 % ( control group ) , with cotinine-vali date d rates of 12.2 % and 7.1 % , respectively ( P = 0.13 ) . Prolonged abstinence rates were significantly different between groups at 3 , 6 , and 12 months ( P < 0.02 ) . Logistic regression analyses indicated adjusted odds of cotinine-vali date d quitting was associated with cigarette consumption per day ( odds ratio , 0.94 ; 95 % confidence interval , 0.89 - 0.99 ) and Center for Epidemiologic Studies Depression Scale score ≥ 16 ( odds ratio , 0.39 ; 95 % confidence interval , 0.17 - 0.90 ) . Conclusions : A lay-led approach that is managed by a nurse may serve as an effective cessation strategy among this high-risk population . Additional efforts are needed to sustain long-term abstinence , even after intensive intervention . ( Cancer Epidemiol Biomarkers Prev 2009;18(12):3451–8 ABSTRACT BACKGROUND Varenicline may be associated with greater mood disturbance and side-effects among smokers with psychiatric history , but empirical evidence is limited . Differential treatment effectiveness by psychiatric history may also exist . OBJECTIVE To compare mood , prevalence and intensity of treatment side-effects , and abstinence among people with a probable history of major depression ( DH+ ) or not ( DH− ) who took varenicline and received behavioral smoking cessation treatment . DESIGN Smokers participated in a r and omized behavioral intervention effectiveness trial . Treatment side-effects and outcomes were compared between DH+ and DH− participants ( n = 1,117 ) at 2 days and 3 months after the target quit date . PARTICIPANTS Smokers recruited from a large regional health plan . MEASUREMENTS Change in stress and depression scores , prevalence and intensity of treatment side-effects , and abstinence rates . RESULTS All side-effects averaged moderate intensity or less and were similar across DH groups , except DH+ ’s endorsed slightly worse confusion , nausea ( adjusted P = 0.04 ) and trouble sleeping ( adjusted P = 0.008 ) at 21 days . Depression and stress scores declined in both DH groups and an equal proportion of each evidence d new/worsening depressive symptoms . Despite few differences in symptom intensity , more DH+ participants reported recent tension/agitation , irritability/anger , confusion , and depression at 21 days ( adjusted P < 0.05 ) , and depression and anxiety ( adjusted P < 0.01 ) at three months . Nonsmoking rates did not differ by DH group at follow-up . CONCLUSION While some group differences were noted , DH+ smokers did not report qualitatively worse neuropsychiatric symptoms , more new/worsening mood disturbance , or differential abstinence rates compared to DH- smokers BACKGROUND : While surgery and perioperative smoking cessation interventions may motivate patients to quit smoking in the short term , it is unknown how often this translates into permanent cessation . In this study , we sought to determine the rates of long-term smoking cessation after a perioperative smoking cessation intervention and predictors of successful cessation at 1 year . METHODS : We previously reported short-term results from a perioperative r and omized controlled trial comparing usual care with an intervention involving ( 1 ) brief counseling by the preadmission nurse , ( 2 ) smoking cessation brochures , ( 3 ) referral to a telephone quitline , and ( 4 ) a free 6-week supply of transdermal nicotine replacement . We now report our 1-year follow-up outcomes . RESULTS : Between October 2010 and April 2012 , 168 patients were r and omized . At 1 year , 127 patients ( 76 % ) were available for follow-up telephone interview . Smoking cessation occurred in 8 % of control patients compared with 25 % of patients in the intervention group ( relative risk , 3.0 ; 95 % confidence interval [ CI ] , 1.2–7.8 ; P = 0.018 ) . The number needed-to-treat to achieve smoking cessation for 1 patient at 1 year postoperatively was 5.9 ( 95 % CI , 3.4–25.9 ) . Multivariable logistic regression modeling found that the intervention ( P = 0.020 ) and lower nicotine dependency at baseline ( P < 0.001 ) were predictive of success at smoking cessation at 1 year . Poisson regression showed that adjusted for nicotine dependency , those r and omized to the intervention group were 2.7 times ( 95 % CI , 1.1–6.7 ; P = 0.028 ) more likely to achieve long-term cessation than those in the control group . Adjusted for r and omization group , a low level of nicotine dependency result ed in a relative risk of quitting of 5.1 ( 95 % CI , 2.0–12.8 ; P = 0.001 ) . CONCLUSIONS : This study demonstrates that an intervention design ed for a busy preadmission clinic results in decreased smoking rates not only around the time of surgery but also continued benefit in smoking cessation at 1 year . Perioperative care providers have a unique opportunity to assist patients in smoking cessation and achieve long-lasting results OBJECTIVE To assess the impact and costs of coverage for tobacco dependence treatment benefits with no patient cost sharing for smokers with employer sponsored coverage in two large independent practice association ( IPA ) model health maintenance organisations ( HMOs ) in California , USA . METHODS A r and omised experimental design was used . 1204 eligible smokers were r and omly assigned either to the control group , which received a self-help kit ( video and pamphlet ) , or to the treatment group , which received the self-help kit and fully covered benefits for over the counter ( OTC ) nicotine replacement therapy ( NRT ) gum and patch , and participation in a group behavioural cessation programme with no patient cost sharing . RESULTS The quit rates after one year of follow up were 18 % in the treatment group and 13 % in the control group ( adjusted odd ratio ( OR ) 1.6 , 95 % confidence interval ( CI ) 1.1 to 2.4 ) , controlling for health plan , sociodemographics , baseline smoking characteristics , and use of bupropion . Rates of quit attempts ( adjusted OR 1.4 , 95 % CI 1.1 to 1.8 ) and use of nicotine gum or patch ( adjusted OR 2.3 , 95 % CI 1.6 to 3.2 ) were also higher in the treatment group . The annual cost of the benefit per user who quit ranged from $ 1495 to $ 965 or from $ 0.73 to $ 0.47 per HMO member per month . CONCLUSIONS Full coverage of a tobacco dependence treatment benefit implemented in two IPA model HMOs in California has been shown to be an effective and relatively low cost strategy for significantly increasing quit rates , quit attempts , and use of nicotine gum and patch in adult smokers The benefits of smoking cessation on patients ' medical conditions are well documented . Cardiovascular patients who quit smoking significantly reduce their risk of a new event compared with those who continue smoking . Several studies have found that smoking is related to poor quality of life ( QoL ) . In cardiovascular patients , however , less attention has been given to the effect of smoking cessation on patients ' QoL. The present study examined the extent to which smoking cessation leads to changes in QoL in these patients within the first year of follow-up . Data were collected in the context of a r and omized clinical trial . Smoking out patients ( N = 346 ) with atherosclerotic disease were included and received medical treatment . They were r and omized to receive either nicotine replacement therapy ( NRT ) or NRT plus a behavioral intervention meant to promote smoking cessation . At baseline , sociodemographic and clinical characteristics were established . Generic and disease-specific QoL as well as smoking status were assessed at baseline and with three follow-up measurements . Multilevel modeling showed that generic and disease-specific QoL in atherosclerotic patients improved significantly within the first year of follow-up . No main differences were found between quitters and smokers in terms of improvement in QoL. In fact , some subgroups reported a poorer QoL after smoking cessation : More highly educated patients reported lower general QoL ( p < .05 ) , and patients suffering from coronary artery disease who had a low level of education ( p < .01 ) and patients suffering from peripheral arterial disease who had low nicotine dependency ( p < .01 ) reported lower disease-specific QoL. Atherosclerotic patients ' QoL improved significantly but was not enhanced by smoking cessation activities Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a r and omized , placebo-controlled clinical trial among adult daily smokers . Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated , relative to a placebo medication and assessment control condition . Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment , relative to the placebo medication conditions , for both biochemically confirmed 7-day point-prevalence abstinence ( OR = 1.97 , 95 % CI 1.04 - 3.72 ) and self-reported prolonged abstinence ( OR = 2.90 , 95 % CI 1.66 - 5.06 ) . Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses . Medication effects were more modest for both 12-month point-prevalence abstinence ( OR = 1.47 , 95 % CI 0.74 - 2.92 ) and prolonged abstinence ( OR = 1.34 , 95 % CI 0.66 - 2.72 ) . Counseling was not associated with increases in the likelihood of abstinence at any time point ( odds ratios ranged from 0.80 to 1.16 across abstinence outcomes in the full intent-to-treat sample ) . Counseling and medication did not significantly interact at any time point , and adding counseling did not improve end-of-treatment point-prevalence abstinence ( OR = 1.17 , 95 % CI 0.68 - 2.03 ) or prolonged abstinence ( OR = 1.26 , 95 % CI 0.75 - 2.12 ) substantially when offered in conjunction with active medication The National Drug Abuse Treatment Clinical Trials Network ( CTN ) recently completed a r and omized , open label trial comparing treatment as usual ( TAU ) combined with nicotine patches plus cognitive behavioral group counseling for smoking cessation ( n = 153 ) to TAU alone ( n = 72 ) for patients enrolled in treatment programs for drug or alcohol dependence , who were interested in quitting smoking . This report is a secondary analysis evaluating the effect of depressive symptomatology ( n = 70 ) or history of depression ( n = 110 ) on smoking cessation outcomes . A significant association was seen between measures of depression and difficulty quitting cigarettes . Specifically , there was a greater probability for smoking abstinence for those with lower baseline Beck Depression Inventory II ( BDI-II ) scores . These data suggest that evaluation and treatment of depressive symptoms may play an important role in improving smoking cessation outcomes . ( Am J Addict 2010;00:1 - 8 ) BACKGROUND Health promotion efforts encourage smokers to quit and to use effective cessation treatments . R and omized controlled trials demonstrate that medications and behavioral treatments improve cessation rates , but retrospective surveys have been inconsistent . This study assessed frequency of quit attempts , use of treatments for cessation , and abstinence rates among treatment users and non-users . METHODS Data were analyzed from the 2003 Tobacco Use Special Cessation Supplement to the Current Population Survey . Participants included 29,537 U.S. smokers aged > or = 18 years who smoked daily 12 months before the survey . Outcome measures included past-year quit attempts ; use of behavioral , pharmacologic , and alternative treatments ; receipt of social support ; and abstinence for > or = 4 weeks at time of survey . RESULTS Approximately 43.5 % of smokers reported a quit attempt in the preceding year : 64.2 % of attempters used no cessation treatments ; 8.8 % used behavioral treatment ; 32.2 % used medication ; and 14.1 % used more than one treatment . Social support was reported to have been received by 24.1 % . More nicotine-dependent smokers were more likely to use medications ( OR=3.58 ; 95 % CI=3.04 - 4.20 ) . At the time of the survey , 19.3 % of attempters were abstinent > or = 4 weeks . Smokers who sought treatment were less likely to be abstinent ( OR=0.75 ; 95 % CI=0.67 - 0.84 ) , and those who sought multiple treatments were even less likely to be abstinent . CONCLUSIONS Many U.S. smokers make quit attempts , but most do not use behavioral or pharmacologic treatments . More nicotine-dependent smokers were more likely to seek treatment . Smokers who sought treatment were less likely to report abstinence , probably due to biased self- selection and recall . Retrospective survey data are not well-suited to assess the effectiveness of treatment BACKGROUND Smokers are more prone to develop postoperative complications . Smoking cessation intervention beginning 4 - 8 weeks prior to surgery improves the postoperative outcome . Cancer patients , however , often undergo surgery less than 4 weeks after diagnosis . The primary objective of this study was therefore to examine if a brief smoking cessation intervention shortly before breast cancer surgery would influence postoperative complications and smoking cessation . METHODS A r and omized controlled multicentre trial with blinded outcome assessment conducted at 3 hospitals in Denmark . One hundred and thirty patients were r and omly assigned to brief smoking intervention ( n = 65 ) or st and ard care ( n = 65 ) . The intervention followed the principles of motivational interviewing and included personalized nicotine replacement therapy aim ed at supporting smoking cessation from 2 days before to 10 days after surgery . RESULTS The overall postoperative complication rate ( including seroma requiring aspiration ) was 61 % in both groups risk ratio ( RR ) 1.00 ( 95 % CI 0.75 - 1.33 ) . The wound complication rate was 44 % versus 45 % . The effect on perioperative smoking cessation was modest , 28 % intervention versus 11 % control group patients , RR 2.49 ( 95 % CI 1.10 - 5.60 ) . There was no effect on smoking cessation at 12 months , 13 % versus 9 % . CONCLUSIONS Brief smoking intervention administered shortly before breast cancer surgery modestly increased self-reported perioperative smoking cessation without having any clinical impact on postoperative complications . The study adds to the body of evidence indicating that brief intervention has no clinical importance for surgical patients in regard to postoperative morbidity . Future studies should be design ed to determine the optimal time of smoking cessation before surgery OBJECTIVES We tested the efficacy of a combined pharmacologic and behavioral smoking cessation intervention among women in a state prison in the southern United States . METHODS The study design was a r and omized controlled trial with a 6-month waitlist control group . The intervention was a 10-week group intervention combined with nicotine replacement therapy . Two hundred and fifty participants received the intervention , and 289 were in the control group . Assessment s occurred at baseline ; end of treatment ; 3 , 6 , and 12 months after treatment ; and at weekly sessions for participants in the intervention group . RESULTS The intervention was efficacious compared with the waitlist control group . Point prevalence quit rates for the intervention group were 18 % at end of treatment , 17 % at 3-month follow-up , 14 % at 6-month follow-up , and 12 % at 12-month follow-up , quit rates that are consistent with outcomes from community smoking-cessation interventions . CONCLUSIONS Female prisoners are interested in smoking cessation interventions and achieved point-prevalence quit rates similar to community sample s. Augmenting tobacco control policies in prison with smoking cessation interventions has the potential to address a significant public health need PURPOSE Cancer survivors smoke at rates that are only slightly lower than the general population . This article reports on the final outcomes of Partnership for Health , a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study ( CCSS ) . METHODS This study is a r and omized control trial with follow-up at 8 and 12 months that involved smokers ( n = 796 ) enrolled onto the CCSS cohort . Participants were r and omly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor , tailored and targeted material s , and free nicotine replacement therapy . The intervention was delivered by telephone and postal service mail . RESULTS The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month ( 16.8 % v 8.5 % ; P < .01 ) and 12-month follow-ups ( 15 % v 9 % ; P < or = .01 ) . Controlling for baseline self-efficacy and readiness to change , the intervention group was twice as likely to quit smoking , compared with the self-help group . Smoking cessation rate increased with an increase in the number of counseling calls . The cost of delivering the intervention was approximately 300 dollars per participant . The incremental cost-effectiveness of the intervention compared with controls was 5,371 dollars per additional quit . CONCLUSION Interventions to prevent future illnesses are of critical importance to childhood cancer survivors . The Partnership for Health intervention result ed in a doubling of smoking cessation quit rates . Because of the seriousness of smoking among childhood cancer survivors , this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke Nicotine dependence is highly prevalent among drug- and alcohol-dependent patients . A multisite clinical trial of smoking cessation ( SC ) treatment was performed at outpatient community-based substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment , Clinical Trials Network . Cigarette smokers ( N=225 ) from five methadone maintenance programs and two drug and alcohol dependence treatment programs were r and omly assigned in a 2:1 ratio to receive either ( 1 ) SC treatment as an adjunct to substance abuse treatment-as-usual ( TAU ) or ( 2 ) substance abuse TAU . Smoking cessation treatment consisted of 1 week of group counseling before the target quit date and 8 weeks of group counseling plus transdermal nicotine patch treatment ( 21 mg/day for Weeks 1 - 6 and 14 mg/day for Weeks 7 and 8) after the target quit date . Smoking abstinence rates in SC , 10%-11 % during treatment and 5%-6 % at the 13- and 26-week follow-up visits , were significantly better than those in TAU during treatment ( p < .01 ) . In addition , SC was associated with significantly greater reductions as compared with TAU in cigarettes smoked per day ( 75 % reduction , p < .001 ) , exhaled carbon monoxide levels ( p < .001 ) , cigarette craving ( p < .05 ) , and nicotine withdrawal ( p < .05 ) . Smoking cessation did not differ from TAU on rates of retention in substance abuse treatment , abstinence from primary substance of abuse , and craving for primary substance of abuse . Compliance with SC treatment , moderate at best , was positively associated with smoking abstinence rates . Smoking cessation treatment result ed in significant reductions in daily smoking and modest smoking abstinence rates without having an adverse impact on substance abuse rehabilitation when given concurrently with outpatient substance abuse treatment . Substance abuse treatment programs should not hesitate to implement SC for established patients This study examined whether therapist behaviors consistent with motivational interviewing ( MI ) were associated with within-session working alliance and client engagement . Forty-six audiotaped counseling sessions were drawn from a group-r and omized comparison-controlled smoking cessation trial for public housing residents . Separate raters coded therapist behaviors and client behaviors . Therapist behaviors were coded using the Motivational Interviewing Skill Code . Results indicated that an MI-consistent style ( average of the global ratings of collaboration , egalitarianism , and empathy ) was positively associated with alliance and engagement , whereas confrontation was negatively related to alliance . Small to moderate effect sizes were found for affirming , asking open-ended questions , confronting , reflecting , and summarizing . Significant covariates include treatment condition , session sequence , and session date . Findings empirically support Miller and Rollnick 's [ Miller , W. R. , & Rollnick , S. ( 2002 ) . Motivational interviewing : Preparing people for change ( 2nd ed . ) . New York : Guilford Press ] emphasis on the importance of MI spirit for enhancing alliance and engagement and their findings that any tears/ruptures in the alliance through the use of confrontation could significantly relate to poor outcomes Background Smoking is an important risk factor for recurrent events in cardiovascular patients . Evidence exists that nicotine replacement therapy ( NRT ) approximately doubles smoking cessation rates . The minimal intervention strategy ( MIS ) has been used successfully to assist patients to quit smoking in general practice , and was recently adapted for cardiology in patients ( C-MIS ) . It is hypothesized that in cardiovascular out patients the combination of C-MIS and NRT significantly increases the number of quitters compared to NRT alone . Methods A r and omized clinical trial in 385 smoking patients who attended the cardiovascular outpatient departments in the Academic Medical Centre , Amsterdam for the treatment of atherosclerotic disease . Patients were allocated to either NRT + C-MIS or NRT alone . Self-reported and biochemically vali date d abstinence rates were measured at 12 months ' follow-up . Results Including patients with incomplete follow-up as smokers , abstinence was reported by 19 % of the NRT + C-MIS group and 14 % of the NRT group [ absolute risk reduction ( ARR ) = 0.05 ; 95 % confidence interval ( CI ) = −0.02 ; 0.12 ] . According to biochemical markers , abstinence rates were 28 and 24 % , respectively ( ARR = 0.04 , 95 % CI = −0.06 ; 0.14 ) . Hence , no significant differences between groups were found . The number of cigarettes smoked a day decreased significantly at 12 months : from 21 to 15 a day in the experimental group , and from 21 to 14 in the control group ( P<0.001 ) , but did not differ between groups ( P=0.32 ) . Conclusions The effectiveness of a minimal contact intervention was investigated in order to reach as many cardiovascular patients as possible in the setting of outpatient departments . This intervention was not found to be effective Background The objectives of this smoking cessation study among hospitalized smokers are to : 1 ) determine provider and patient receptivity , barriers , and facilitators to implementing the nurse-administered , inpatient Tobacco Tactics intervention versus usual care using face-to-face feedback and surveys ; 2 ) compare the effectiveness of the nurse-administered , inpatient Tobacco Tactics intervention versus usual care across hospitals , units , and patient characteristics using thirty-day point prevalence abstinence at thirty days and six months ( primary outcome ) post-recruitment ; and 3 ) determine the cost-effectiveness of the nurse-administered , inpatient Tobacco Tactics intervention relative to usual care including cost per quitter , cost per life-year saved , and cost per quality -adjusted life-year saved . Methods / Design This effectiveness study will be a quasi-experimental design of six Michigan community hospitals of which three will get the nurse-administered Tobacco Tactics intervention and three will provide their usual care . In both the intervention and usual care sites , research assistants will collect data from patients on their smoking habits and related variables while in the hospital and at thirty days and six months post-recruitment . The intervention will be integrated into the experimental sites by a research nurse who will train Master Trainers at each intervention site . The Master Trainers , in turn , will teach the intervention to all staff nurses . Research nurses will also conduct formative evaluation with nurses to identify barriers and facilitators to dissemination . Descriptive statistics will be used to summarize the results of surveys administered to nurses , nurses ’ participation rates , smokers ’ receipt of specific cessation services , and satisfaction with services . General estimating equation analyses will be used to determine differences between intervention groups on satisfaction and quit rates , respectively , with adjustment for the clustering of patients within hospital units . Regression analyses will test the moderation of the effects of the interventions by patient characteristics . Cost-effectiveness will be assessed by constructing three ratios including cost per quitter , cost per life-year saved , and cost per quality -adjusted life-year saved . Discussion Given that nurses represent the largest group of front-line providers , this intervention , if proven effective , has the potential for having a wide reach and thus decrease smoking , morbidity and mortality among inpatient smokers . Trial registration Dissemination of Tobacco Tactics for Hospitalized Smokers Background Although smoking prevalence remains strikingly high in homeless population s ( ~70 % and three times the US national average ) , smoking cessation studies usually exclude homeless persons . Novel evidence -based interventions are needed for this high-risk sub population of smokers . Purpose To describe the aims and design of a first-ever smoking cessation clinical trial in the homeless population . The study was a two-group r and omized community-based trial that enrolled participants ( n = 430 ) residing across eight homeless shelters and transitional housing units in Minnesota . The study objective was to test the efficacy of motivational interviewing ( MI ) for enhancing adherence to nicotine replacement therapy ( NRT ; nicotine patch ) and smoking cessation outcomes . Methods Participants were r and omized to one of the two groups : active ( 8 weeks of NRT + 6 sessions of MI ) or control ( NRT + st and ard care ) . Participants attended six in-person assessment sessions and eight retention visits at a location of their choice over 6 months . Nicotine patch in 2-week doses was administered at four visits over the first 8 weeks of the 26-week trial . The primary outcome was cotinine-verified 7-day point-prevalence abstinence at 6 months . Secondary outcomes included adherence to nicotine patch assessed through direct observation and patch counts . Other outcomes included the mediating and /or moderating effects of comorbid psychiatric and substance abuse disorders . Results Lessons learned from the community-based cessation r and omized trial for improving recruitment and retention in a mobile and vulnerable population included : ( 1 ) the importance of engaging the perspectives of shelter leadership by forming and convening a Community Advisory Board ; ( 2 ) locating the study at the shelters for more visibility and easier access for participants ; ( 3 ) minimizing exclusion criteria to allow enrollment of participants with stable psychiatric comorbid conditions ; ( 4 ) delaying the baseline visit from the eligibility visit by a week to protect against attrition ; and ( 5 ) regular and persistent calls to remind participants of upcoming appointments using cell phones and shelter-specific channels of communication . Limitations The study ’s limitations include generalizability due to the sample drawn from a single Midwestern city in the United States . Since inclusion criteria encompassed willingness to use NRT patch , all participants were motivated and were ready to quit smoking at the time of enrollment in the study . Findings from the self-select group will be generalizable only to those motivated and ready to quit smoking . High incentives may limit the degree to which the intervention is replicable . Conclusions Lessons learned reflect the need to engage communities in the design and implementation of community-based clinical trials with vulnerable population AIMS To assess the effectiveness of an intensive smoking cessation intervention based on the transtheoretical model of change ( TTM ) in diabetic smokers attending primary care . METHODS A cluster r and omized controlled clinical trial was design ed in which the unit of r and omization ( intervention vs. usual care ) was the primary care team . An intensive , individualized intervention using motivational interview and therapies and medications adapted to the patient 's stage of change was delivered . The duration of the study was 1 year . RESULTS A total of 722 people with diabetes who were smokers ( 345 in the intervention group and 377 in the control group ) completed the study . After 1 year , continued abstinence was recorded in 90 ( 26.1 % ) patients in the intervention group and in 67 ( 17.8 % ) controls ( p=0.007 ) . In patients with smoking abstinence , there was a higher percentage in the precontemplation and contemplation stages at baseline in the intervention group than in controls ( 21.2 % vs. 13.7 % , p=0.024 ) . When the precontemplation stage was taken as reference ( OR=1.0 ) , preparation/action stage at baseline showed a protective effect , decreasing 3.41 times odds of continuing smoking ( OR=0.293 95 % CI 0.179 - 0.479 , p<0.001 ) . Contemplation stage at baseline also showed a protective effect , decreasing the odds of continuing smoking ( OR=0.518 , 95 % CI 0.318 - 0.845 , p=0.008 ) . CONCLUSIONS An intensive intervention adapted to the individual stage of change delivered in primary care was feasible and effective , with a smoking cessation rate of 26.1 % after 1 year AIMS To examine the effectiveness of smoking reduction counselling plus free nicotine replacement therapy ( NRT ) for smokers not willing to quit . DESIGN , SETTING AND PARTICIPANTS A total of 1154 Chinese adult smokers not willing to quit but who were interested in reducing smoking were allocated r and omly to three arms . Intervention group A1 ( n=479 ) received face-to-face counselling on smoking reduction and adherence to NRT at baseline , 1 week and 4 weeks with 4 weeks of free NRT . Group A2 ( n=449 ) received the same intervention , but without the adherence intervention . Control group B ( n=226 ) received simple cessation advice at baseline . MEASUREMENTS Self-reported 7-day point prevalence of tobacco abstinence and reduction of cigarette consumption ( ≥50 % ) at 6 months and continuous use of NRT for 4 weeks at 3 months . FINDINGS Using intention-to-treat analysis , compared to control group B , the intervention groups ( A1+A2 ) had achieved higher 6-month tobacco abstinence ( 17.0 % versus 10.2 % , P=0.01 ) and reduction rates ( 50.9 % versus 25.7 % , P<0.001 ) . There was no significant difference in the 4-week NRT adherence rate at 3 months , but group A1 achieved a higher abstinence rate than group A2 at 6 months ( 20.9 % versus 12.9 % ; P=0.001 ) . CONCLUSIONS In smokers with no immediate plans to quit , smoking reduction programmes with behavioural support and nicotine replacement therapy are more effective than brief advice to quit . Current guidelines recommend advice to quit on medical grounds as the best clinical intervention in this group of smokers , but smoking reduction programmes offer an alternative and effective option BACKGROUND Brief clinician intervention and telephone counseling are both effective aids for smoking cessation . However , the potential benefit of telephone care above and beyond routine clinician intervention has not been examined previously . The objective of this study is to determine if telephone care increases smoking cessation compared with brief clinician intervention as part of routine health care . METHODS This 2-group , prospect i ve , r and omized controlled trial enrolled 837 daily smokers from 5 Veterans Affairs medical centers in the upper Midwest . The telephone care group ( n = 417 ) received behavioral counseling with mailing of smoking cessation medications as clinical ly indicated . The st and ard care group ( n = 420 ) received intervention as part of routine health care . The primary outcome was self-reported 6-month duration of abstinence 12 months after enrollment . Secondary outcomes were 7-day point prevalence abstinence at 3 and 12 months , participation in counseling programs , and use of smoking cessation medications . RESULTS Using intention-to-treat procedures , we found that the rate of 6-month abstinence at the 12-month follow-up was 13.0 % in the telephone care group and 4.1 % in the st and ard care group ( odds ratio [ OR ] , 3.50 ; 95 % confidence interval [ CI ] , 1.99 - 6.15 ) . The rate of 7-day point prevalence abstinence at 3 months was 39.6 % in the telephone care group and 10.1 % in the st and ard care group ( OR , 5.84 ; 95 % CI , 4.02 - 8.50 ) . Telephone care compared with st and ard care increased the rates of participation in counseling programs ( 97.1 % vs 24.0 % ; OR , 96.22 ; 95 % CI , 52.57 - 176.11 ) and use of smoking cessation medications ( 89.6 % vs 52.3 % ; OR , 7.85 ; 95 % CI , 5.34 - 11.53 ) . CONCLUSION Telephone care increases the use of behavioral and pharmacologic assistance and leads to higher smoking cessation rates compared with routine health care provider intervention Pharmacological interventions for smoking cessation are typically evaluated using volunteer sample s ( efficacy trials ) but should also be evaluated in population -based trials ( effectiveness trials ) . Nicotine replacement therapy ( NRT ) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New Engl and Veterans Affairs Medical Center . Telephone interviews were completed with 3,239 smokers , and 2,054 agreed to participate ( 64 % ) . Participants were r and omly assigned to one of four conditions : stage-matched manuals ( MAN ) ; NRT plus manuals ( NRT + MAN ) ; expert system plus NRT and manuals ( EXP + NRT + MAN ) ; and automated counseling plus NRT , manuals , and expert system ( TEL + EXP + NRT + MAN ) . Assessment s were completed at baseline , 10 , 20 , and 30 months . The point prevalence cessation rates at final follow-up ( 30 months ) were MAN , 20.3 % ; NRT + MAN , 19.3 % ; EXP + NRT + MAN , 17.6 % ; and TEL + EXP + NRT + MAN , 19.9 % . Stage-matched manuals provided cessation rates comparable with previous studies . The addition of NRT , expert system interventions , and automated telephone counseling failed to produce a further increase in intervention effectiveness BACKGROUND This paper investigates individual patient characteristics predicting differential response to each of three physician-delivered smoking interventions after 6 months . METHODS Participants were 1,286 currently smoking patients seen by 196 medical and family practice residents in five primary care clinics affiliated with the University of Massachusetts Medical School . Of the participants , 57 % were female , 92 % were white , their average age was 35 years , and they smoked an average of 23 cigarettes per day . Physicians were trained to provide the following interventions : advice only ( AO ) , a brief ( < 10 min ) patient-centered counseling intervention ( CI ) , and counseling plus prescription of the nicotine-containing gum Nicorette ( CI+NCG ) . The CI+NCG condition included NCG only when appropriate and if acceptable to the patient . Patients were r and omized to one of these three physician-delivered intervention conditions . RESULTS Overall , stratified univariate analyses revealed that AO produced consistently lower cessation rates across most subgroups ( generally 9 - 13 % ) but was somewhat more effective for certain groups of lighter smokers . Relative to AO , CI was somewhat more effective ( about 20 - 24 % ) for less addicted smokers , for those with more previous quit attempts , and for those with fewer close associates who smoke , but generally failed to produce higher quit rates for harder core smokers or for women . CI+NCG had an overall pattern of greater effectiveness for both more addicted and less addicted smokers , with the highest absolute levels of cessation ( about 27 - 30 % ) among less dependent smokers . Women in this group had cessation rates ( 20.6 % ) comparable to those of men ( 23.6 % ) . Condition-stratified logistic regression analyses , controlling for a wide range of covariates , revealed associations similar to those observed in the univariate analyses : An overall logistic model in which intervention conditions were fitted as dummy variables produced the following significant main effects : sex , years smoked , contact with other smokers , symptoms , and CI+NCG condition . Significant interactions were observed for both CI and CI+NCG and smoking when feeling too ill to continue normal activities and CI+NCG and amount smoked . CONCLUSIONS We observed significant main effects on cessation of variables related to addiction , sex , social factors , and physician counseling interventions . Specific interactions were observed between reported smoking when feeling ill and each of the counseling interventions as well as by amount smoked in the CI+NCG condition Background The use of spirometry for early detection of chronic obstructive pulmonary disease ( COPD ) is still an issue of debate , particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation . We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed " confrontational counselling " ; a patient-centred approach which involves specific communication skills and elements of cognitive therapy . An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions . The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation . Methods / Design The study design is a r and omized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( experimental group ) , health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( control group 1 ) , and " care as usual " delivered by the GP ( control group 2 ) . Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry . Due to a comparable baseline risk of airflow limitation and motivation to quit smoking , and because of the st and ardization of number , duration , and scheduling of counselling sessions between the experimental group and control group 1 , the study enables to assess the " net " effect of confrontational counselling . The study has been ethically approved and registered . Discussion Ethical as well as method ological considerations of the study are discussed in this protocol . A significant and relevant effect of confrontational counselling would provide an argument in favour of early detection of current smokers with airflow limitation . Successful treatment of tobacco dependence in respiratory patients requires repeated intensive interventions . The results of this study may also show that respiratory nurses are able to deliver this treatment and that intensive smoking cessation counselling is more feasible . Trial registration : Netherl and s Trial Register ( IS RCT N 64481813 ) Background A hospital admission offers smokers an opportunity to quit . Smoking cessation counseling provided in the hospital is effective , but only if it continues for more than one month after discharge . Providing smoking cessation medication at discharge may add benefit to counseling . A major barrier to translating this research into clinical practice is sustaining treatment during the transition to outpatient care . An evidence -based , practical , cost-effective model that facilitates the continuation of tobacco treatment after discharge is needed . This paper describes the design of a comparative effectiveness trial testing a hospital-initiated intervention against st and ard care . Methods / design A two-arm r and omized controlled trial compares the effectiveness of st and ard post-discharge care with a multi-component smoking cessation intervention provided for three months after discharge . Current smokers admitted to Massachusetts General Hospital who receive bedside smoking cessation counseling , intend to quit after discharge and are willing to consider smoking cessation medication are eligible . Study participants are recruited following the hospital counseling visit and r and omly assigned to receive St and ard Care or Extended Care after hospital discharge . St and ard Care includes a recommendation for a smoking cessation medication and information about community re sources . Extended Care includes up to three months of free FDA -approved smoking cessation medication and five proactive computerized telephone calls that use interactive voice response technology to provide tailored motivational messages , offer additional live telephone counseling calls from a smoking cessation counselor , and facilitate medication refills . Outcomes are assessed at one , three , and six months after hospital discharge . The primary outcomes are self-reported and vali date d seven-day point prevalence tobacco abstinence at six months . Other outcomes include short-term and sustained smoking cessation , post-discharge utilization of smoking cessation treatment , hospital readmissions and emergency room visits , and program cost per quit . Discussion This study tests a disseminable smoking intervention model for hospitalized smokers . If effective and widely adopted , it could help to reduce population smoking rates and thereby reduce tobacco-related mortality , morbidity , and health care costs . Trial registration United States Clinical Trials Registry NCT01177176 Objectives : State and national tobacco quitlines have exp and ed rapidly and offer a range of services . We examined the effectiveness and cost effectiveness of offering callers single session versus multisession counselling , with or without free nicotine patches . Methods : This 3 × 2 r and omised trial included 4614 Oregon tobacco quitline callers and compared brief ( one 15-minute call ) , moderate ( one 30-minute call and a follow-up call ) and intensive ( five proactive calls ) intervention protocol s , with or without offers of free nicotine patches ( nicotine replacement therapy , NRT ) . Blinded staff assessed tobacco use by phone at 12 months . Results : Abstinence odds ratios were significant for moderate ( OR = 1.22 , CI = 1.01 to 1.48 ) and intensive ( OR = 1.29 , CI = 1.07 to 1.56 ) intervention , and for NRT ( OR = 1.58 , CI = 1.35 to 1.85 ) . Intent to treat quit rates were as follows : brief no NRT ( 12 % ) ; brief NRT ( 17 % ) ; moderate no NRT ( 14 % ) ; moderate NRT ( 20 % ) ; intensive no NRT ( 14 % ) ; and intensive NRT ( 21 % ) . Relative to brief no NRT , the added costs for each additional quit was $ 2467 for brief NRT , $ 1912 for moderate no NRT , $ 2109 for moderate NRT , $ 2641 for intensive no NRT , and $ 2112 for intensive NRT . Conclusion : Offering free NRT and multisession telephone support within a state tobacco quitline led to higher quit rates , and similar costs per incremental quit , than less intensive protocol Background There is a high prevalence of smoking and high burden of tobacco-related diseases among low-income population s. Effective , evidence d-based smoking cessation treatments are available , but low-income smokers are less likely than higher-income smokers to use these treatments , especially the most comprehensive forms that include a combination of pharmacotherapy and intensive behavioral counseling . Methods / Design The primary objectives of this r and omized controlled trial are to compare the effects of a proactive tobacco treatment intervention compared to usual care on population -level smoking abstinence rates and tobacco treatment utilization rates among a diverse population of low-income smokers , and to determine the cost-effectiveness of proactive tobacco treatment intervention . The proactive care intervention systematic ally offers low-income smokers free and easy access to evidence -based treatments and has two primary components : ( 1 ) proactive outreach to current smokers in the form of mailed invitation material s and telephone calls containing targeted health messages , and ( 2 ) facilitated access to free , comprehensive , evidence -based tobacco cessation treatments in the form of NRT and intensive , telephone-based behavioral counseling . The study aims to include a population -based sample ( N = 2500 ) of adult smokers enrolled in the Minnesota Health Care Programs ( MHCP ) , a state-funded health insurance plan for low-income persons . Baseline data is obtained from MHCP administrative data bases and a participant survey that is conducted prior to r and omization . Outcome data is collected from a follow-up survey conducted 12 months after r and omization and MHCP administrative data . The primary outcome is six-month prolonged smoking abstinence at one year and is assessed at the population level . All r and omized individuals are asked to complete the follow-up survey , regardless of whether they participated in tobacco treatment . Data analysis of the primary aims will follow intent-to-treat methodology . Discussion There is a critical need to increase access to effective tobacco dependence treatments . This r and omized trial evaluates the effects of proactive outreach coupled with free NRT and telephone counseling on the population impact of tobacco dependence treatment . If proven to be effective and cost-effective , national dissemination of proactive treatment approaches would reduce tobacco-related morbidity , mortality , and health care costs for low income Americans . Clinical trials registration Clinical Trials.gov : Lay health advisers ( LHAs ) are increasingly used to deliver tobacco dependence treatment , especially with low-socioeconomic status ( SES ) population s. More information is needed about treatment adherence to help interpret mixed evidence of LHA intervention effectiveness . This study examined adherence to behavioral counseling and nicotine patches in an LHA intervention with 147 Ohio Appalachian female daily smokers . Participants were r and omly selected from clinics and r and omized to the intervention condition of a r and omized controlled trial . Overall , 75.5 % of participants received all seven planned LHA visits , 29.3 % used patches for > 7 weeks and approximately half received high average ratings on participant responsiveness . Depressive symptoms and low nicotine dependence were associated with lower patch adherence while high poverty-to-income ratio was associated with high responsiveness . Compared with those with fewer visits , participants who received all visits were more likely to be abstinent ( 22.5 versus 2.8 % , P=0.026 ) or have attempted quitting ( 85.0 versus 47.4 % , P=0.009 ) at 3 months . High participant responsiveness was associated with 12-month abstinence . LHA interventions should focus on improving adherence to nicotine patches and managing depression because it is an independent risk factor for low adherence Background Hospitalized smokers often quit smoking , voluntarily or involuntarily ; most relapse soon after discharge . Extended follow-up counseling can help prevent relapse . However , it is difficult for hospitals to provide follow-up and smokers rarely leave the hospital with quitting aids ( for example , nicotine patches ) . This study aims to test a practical model in which hospitals work with a state cessation quitline . Hospital staff briefly intervene with smokers at bedside and refer them to the quitline . Depending on assigned condition , smokers may receive nicotine patches at discharge or extended quitline telephone counseling post-discharge . This project establishes a practical model that lends itself to broader dissemination , while testing the effectiveness of the interventions in a rigorous r and omized trial . Methods / design This r and omized clinical trial ( N = 1,640 ) tests the effect of two interventions on long-term quit rates of hospitalized smokers in a 2 x 2 factorial design . The interventions are ( 1 ) nicotine patches ( eight-week , step down program ) dispensed at discharge and ( 2 ) proactive telephone counseling provided by the state quitline after discharge . Subjects are r and omly assigned into : usual care , nicotine patches , telephone counseling , or both patches and counseling . It is hypothesized that patches and counseling have independent effects and their combined effect is greater than either alone . The primary outcome measure is thirty-day abstinence at six months ; a secondary outcome is biochemically vali date d smoking status . Cost-effectiveness analysis is conducted to compare each intervention condition ( patch alone , counseling alone , and combined interventions ) against the usual care condition . Further , this study examines whether smokers ’ medical diagnosis is a moderator of treatment effect . Generalized linear ( binomial ) mixed models will be used to study the effect of treatment on abstinence rates . Clustering is accounted for with hospital-specific r and om effects . Discussion If this model is effective , quitlines across the U.S. could work with interested hospitals to set up similar systems . Hospital accreditation st and ards related to tobacco cessation performance measures require follow-up after discharge and provide additional incentive for hospitals to work with quitlines . The ubiquity of quitlines , combined with the consistency of quitline counseling delivery as central ized state operations , make this partnership attractive . Trial registration Smoking cessation in hospitalized smokers NCT01289275 . Date of registration February 1 , 2011 ; date of first patient August 3 , 2011 BACKGROUND The Lung Health Study ( LHS ) , a 5-year , r and omized , prospect i ve clinical trial , studied the effects of smoking intervention and therapy with inhaled anticholinergic bronchodilators on FEV(1 ) in participants who were 35 to 60 years of age and had mild COPD . Participants were r and omized into the following three groups : usual care ; smoking cessation plus inhaled ipratropium bromide ; and smoking cessation plus placebo inhaler . This report evaluates the effects of these interventions , demographic characteristics , smoking status , and FEV(1 ) changes on airway responsiveness ( AR ) . METHODS AND RESULTS Of 5,887 participants , 4,201 underwent methacholine challenge testing both at study entry and study completion . All groups increased AR during the 5-year period . The increase in AR was greatest in continuing smokers and was associated with a greater FEV(1 ) decline . An intent-to-treat analysis indicated no significant differences in AR changes among the three groups . CONCLUSIONS Changes in AR over a 5-year period in the LHS were primarily related to changes in the FEV(1 ) . The greater the decline in FEV(1 ) , the greater the increase in AR . Smoking cessation had a small additional benefit in AR beyond its favorable effects on FEV(1 ) changes Objectives To investigate the effectiveness of the systematic default provision of smoking cessation support to all adult smokers admitted to hospital , relative to usual care . Design Open , cluster r and omised controlled trial . Setting Acute medical wards in one large teaching hospital in the United Kingdom . Participants 264 patients r and omised to intervention and 229 to usual care ; primary outcome data were available at four weeks for 260 and 224 patients , respectively . All adult smokers and recent ex-smokers able to give informed consent were eligible for entry into the study . Interventions The intervention comprised systematic smoking ascertainment and default provision of behavioural support and cessation pharmacotherapy for the duration of the hospital stay for all smokers and recent ex-smokers , with follow-up and referral to community services after discharge . Usual care comprised cessation support delivered at the initiative and discretion of clinical staff . All staff and patients were aware of group assignment . Main outcome measures Smoking cessation at four weeks , vali date d by measuring exhaled carbon monoxide . Secondary outcomes were uptake of inpatient behavioural support , use of cessation pharmacotherapy , referral to and uptake of community support after discharge , and vali date d smoking cessation at six months . Participants lost to follow-up were assumed to have reverted to smoking . Results All patients in the intervention group received at least brief advice to quit smoking , compared to 106 ( 46 % ) patients in the usual care group . Cessation at four weeks was achieved by 38 % ( n=98 ) of intervention patients and 17 % ( n=37 ) of usual care patients ( adjusted odds ratio 2.10 ( 95 % confidence interval 0.96 to 4.61 ) , P=0.06 , number of patients needed to treat 8) . Uptake of inpatient behavioural support , use of pharmacotherapy , and referral to and uptake of community support after discharge were all substantially and statistically significantly higher in the intervention group than in the usual care group . Cessation at six months was achieved by 19 % ( n=47 ) of intervention and 9 % ( n=19 ) of usual care patients , although this difference was not significant ( adjusted odds ratio 1.53 ( 95 % confidence interval 0.60 to 3.91 ) ; P=0.37 ) . Conclusions Substantial improvements in smoking cessation among smokers admitted to hospital can be achieved by systematic ascertainment and delivery of cessation support in secondary care . Trial registration International St and ard R and omised Controlled Trial Number IS RCT N25441641 AIM The EUROACTION PLUS trial measured the effectiveness of a nurse-led preventive cardiology programme ( EUROACTION ) offering intensive smoking cessation PLUS optional varenicline for persistent high CVD risk smokers to reduce overall cardiovascular risk compared with usual care ( UC ) in general practice ( GP ) . METHODS AND RESULTS A parallel group r and omized controlled trial in 20 GP in Italy , Netherl and s , Spain , and UK . Six hundred and ninety-six current smokers , ( 137 vascular disease and 559 high total CVD risk ) , were r and omized 350 to EUROACTION PLUS ( EA+ ) and 346 to UC . Specially , trained nurses offered the EUROACTION preventive cardiology programme addressing smoking cessation , diet , physical activity , and risk factor management to reduce overall cardiovascular risk . The primary endpoint was 7 day point prevalence of self-reported abstinence ( vali date d breath carbon monoxide < 10 p.p.m . ) at 16 weeks . Secondary outcomes included dietary habits , physical activity , weight , blood pressure ( BP ) , lipid , and glucose management . One hundred and seventy-seven ( 51 % ) EA+ patients ( 91 % opted to use varenicline ) were abstinent vs. 63 ( 19 % ) in UC ; OR 4.52 ( 95 % CI : 3.20 - 6.39 ) . The Mediterranean diet score of ≥9 in 149 ( 52 % ) EA+ patients vs. 97 ( 37 % ) in UC ; OR 1.84 ( 95 % CI : 1.31 - 2.59 ) . Physical activity target achieved in 46 ( 16 % ) EA+ patients vs. 19 ( 7 % ) in UC ; OR 2.48 ( 95 % CI : 1.41 - 4.36 ) . Target BP ( < 140/90 mm Hg ) achieved in 150 ( 52 % ) EA+ patients vs. 112 ( 43 % ) in UC , OR 1.47 ( 95 % CI : 1.05 - 2.06 ) with no difference in antihypertensive drugs . There were no differences in management of cholesterol or glucose . CONCLUSIONS The EUROACTION preventive cardiology programme in high CVD risk smokers using optional varenicline substantially increased smoking abstinence over 16 weeks and also reduced overall cardiovascular risk compared with UC . REC reference : 09/H0402/85 ; EudraCT number : 2009 - 012451 - 18 ; http://www.controlled-trials.com/IS RCT N22073647 , 12 February 2014 , date last accessed Background It is a priority to achieve smoking cessation in diabetic smokers , given that this is a group of patients with elevated cardiovascular risk . Furthermore , tobacco has a multiplying effect on micro and macro vascular complications . Smoking abstinence rates increase as the intensity of the intervention , length of the intervention and number and diversity of contacts with the healthcare professional during the intervention increases . However , there are few published studies about smoking cessation in diabetics in primary care , a level of healthcare that plays an essential role in these patients . Therefore , the aim of the present study is to evaluate the effectiveness of an intensive smoking cessation intervention in diabetic patients in primary care . Methods / Design Cluster r and omized trial , controlled and multicentric . R and omization unit : Primary Care Team . Study population : 546 diabetic smokers older than 14 years of age whose disease is controlled by one of the primary care teams in the study . Outcome Measures : Continuous tobacco abstinence ( a person who has not smoked for at least six months and with a CO level of less than 6 ppm measured by a cooximeter ) , evolution in the Prochaska and DiClemente 's Transtheoretical Model of Change , number of cigarettes/day , length of the visit . Point of assessment : one- year post- inclusion in the study . Intervention : Brief motivational interview for diabetic smokers at the pre-contemplation and contemplation stage , intensive motivational interview with pharmacotherapy for diabetic smokers in the preparation-action stage and reinforcing intevention in the maintenance stage . Statistical Analysis : A descriptive analysis of all variables will be done , as well as a multilevel logistic regression and a Poisson regression . All analyses will be done with an intention to treatment basis and will be fitted for potential confounding factors and variables of clinical importance . Statistical packages : SPSS15 , STATA10 y HLM6 . Discussion The present study will try to describe the profile of a diabetic smoker who receives the most benefit from an intensive intervention in primary care . The results will be useful for primary care professionals in their usual clinical practice .Trial Registration Clinical Trials.gov Identifier : IMPORTANCE Widening socioeconomic disparities in mortality in the United States are largely explained by slower declines in tobacco use among smokers of low socioeconomic status ( SES ) than among those of higher SES , which points to the need for targeted tobacco cessation interventions . Documentation of smoking status in electronic health records ( EHRs ) provides the tools for health systems to proactively offer tobacco treatment to socioeconomically disadvantaged smokers . OBJECTIVE To evaluate a proactive tobacco cessation strategy that addresses socio context ual mediators of tobacco use for low-SES smokers . DESIGN , SETTING , AND PARTICIPANTS This prospect i ve , r and omized clinical trial included low-SES adult smokers who described their race and /or ethnicity as black , Hispanic , or white and received primary care at 1 of 13 practice s in the greater Boston area ( intervention group , n = 399 ; control group , n = 308 ) . INTERVENTIONS We analyzed EHRs to identify potentially eligible participants and then used interactive voice response ( IVR ) techniques to reach out to them . Consenting patients were r and omized to either receive usual care from their own health care team or enter an intervention program that included ( 1 ) telephone-based motivational counseling , ( 2 ) free nicotine replacement therapy ( NRT ) for 6 weeks , ( 3 ) access to community-based referrals to address socio context ual mediators of tobacco use , and ( 4 ) integration of all these components into their normal health care through the EHR system . MAIN OUTCOMES AND MEASURES Self-reported past-7-day tobacco abstinence 9 months after r and omization ( " quitting " ) , assessed by automated caller or blinded study staff . RESULTS The intervention group had a higher quit rate than the usual care group ( 17.8 % vs 8.1 % ; odds ratio , 2.5 ; 95 % CI , 1.5 - 4.0 ; number needed to treat , 10 ) . We examined whether use of intervention components was associated with quitting among individuals in the intervention group : individuals who participated in the telephone counseling were more likely to quit than those who did not ( 21.2 % vs 10.4 % ; P < .001 ) . There was no difference in quitting by use of NRT . Quitting did not differ by a request for a community referral , but individuals who used their referral were more likely to quit than those who did not ( 43.6 % vs 15.3 % ; P < .001 ) . CONCLUSIONS AND RELEVANCE Proactive , IVR-facilitated outreach enables engagement with low-SES smokers . Providing counseling , NRT , and access to community-based re sources to address socio context ual mediators among smokers reached in this setting is effective . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01156610 OBJECTIVES To investigate the effectiveness of telephone counselling as an adjunct to nicotine replacement therapy ( NRT ) by transdermal patch in smoking cessation . DESIGN R and omised controlled trial . PARTICIPANTS AND SETTING 854 smokers from New South Wales , aged 18 years and older , who had smoked at least 10 cigarettes per day for the past year and responded to newspaper advertisements between October 2001 and January 2002 ; the trial was conducted between October 2001 and August 2002 . INTERVENTIONS R and om allocation to either NRT alone or NRT plus telephone counselling ( 5 sessions spaced according to a relapse-sensitive call schedule ) . MAIN OUTCOME MEASURES Self-reported abstinence assessed by telephone question naires at 1 , 2 , 3 and 6 months : 28-day continuous abstinence at 3 and 6 months , and 90-day continuous abstinence at 6 months . RESULTS 28-day continuous abstinence rates among participants receiving telephone counselling were significantly greater than among those not receiving telephone counselling at both 3 and 6 months ( 31.6 % v 25.1 % ; P = 0.04 at 3 months ; and 30.1 % v 22.4 % ; P = 0.01 at 6 months ) . Similarly , 90-day continuous abstinence rates at 6 months were significantly greater for participants receiving counselling ( 26.7 % v 18.6 % ; P = 0.004 ) . CONCLUSION Telephone counselling as an adjunct to NRT increases abstinence rates beyond the use of NRT alone Background Smoking cessation is a high-priority intervention to prevent CVD events and deaths in developing countries . While several interventions to stop smoking have been proved successful , the question of how to increase their effectiveness and practicality in developing countries remains . In this study , a newly devised evidence -based smoking cessation service package will be compared with the existing service in a r and omized controlled trial within the community setting of Thail and . Method / Design This r and omized control trial will recruit 440 current smokers at CVD risk because of being diabetic and /or hypertensive . Informed , consented participants will be r and omly allocated into the new service-package arm and the routine service arm . The study will take place in the non-communicable disease clinics of the Maetha District Hospital , Lampang , northern Thail and . The new smoking-cessation service-package comprises ( 1 ) regular patient motivation and coaching from the same primary care nurse over a 3-month period ; ( 2 ) monthly application of piCO + smokerlyzer to sustain motivation of smoker ’s quitting attempt and provide positive feedback over a 3-month period ; ( 3 ) assistance by an assigned family member ; ( 4 ) nicotine replacement chewing gum to relieve withdrawal symptoms . This new service will be compared with the traditional routine service comprising the 5A approach in a 1-year follow-up . Participants who consent to participate in the study but refuse to attempt quitting smoking will be allocated to the non-r and omized arm , where they will be just followed up and monitored . Primary outcome of the study is smoking cessation rate at 1-year follow-up proven by breath analysis measuring carbomonoxide in parts per million in expired air . Secondary outcomes are smoking cessation rate at the 6-month follow-up , blood pressure and heart rate , CVD risk according to the Framingham general cardiovascular risk score , CVD events and deaths at the 12-month follow-up , and the cost-effectiveness of the health service packages . Intention-to-treat analysis will be followed . Factors influencing smoking cessation will be analyzed by the structure equation model . Discussion This multicomponent intervention , accessible at primary healthcare clinics , and focusing on the individual as well as the family and social environment , is unique and expected to work effectively . Trial registration Current Controlled Trials IS RCT Background Intensive smoking cessation interventions initiated during hospitalisation are effective , but currently not widely available . Strategies are needed to integrate smoking cessation treatment into routine inpatient care . Pharmacist-led interventions for smoking cessation are feasible and efficacious in both ambulatory and community pharmacy setting s. However , there is a lack of evidence from large scale studies of the effectiveness of pharmacist guided programs initiated during patient hospitalisation in achieving long-term abstinence . This study aims to evaluate the effectiveness of a pharmacist-led system change intervention initiated during hospitalisation in Australian public hospitals . Methods / design A multi-centre , r and omised controlled trial will be conducted with 12 months follow-up . Smokers , 18 years or older , will be recruited from the wards of three Victorian public hospitals . Participants will be r and omly assigned to a usual care or intervention group using a computer generated r and omisation list . The intervention group will receive at least three smoking cessation support sessions by a trained pharmacist : the first during the hospital stay , the second on or immediately after discharge and the third within one month post-discharge . All smoking cessation medications will be provided free of charge during the hospital stay and for at least one week after discharge . Participants r and omised to usual care will receive the current care routinely provided by the hospital . All measurements at baseline , discharge , one , six and 12 months will be performed by a blinded Research Assistant . The primary outcome measures are carbon monoxide vali date d 7-day point prevalence abstinence at six and 12 months . Discussion This is the first large scale study to develop and test a pharmacist-led system change intervention program initiated during patient hospitalisation . If successful , the program could be considered for wider implementation across other hospitals . Trial registration Background Smoking is an important risk factor for cardiovascular disease ( CVD ) , and quitting is highly beneficial . Yet , less than 30 % of CVD patients stop smoking . Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease . Objective A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change . Method Participants ( N = 168 ) were r and omly assigned by cohorts to inpatient counseling with telephone follow-up , inpatient counseling , and usual care . The inpatient intervention consisted of a 1-hr counseling session , and the telephone follow-up included 6 calls during the first 2 months after discharge . The nursing intervention was tailored to the individual 's stage of change . End points at 2 and 6 months included actual and continuous smoking cessation rates ( biochemical markers ) and increased motivation ( progress to ulterior stages of change ) . Results Assuming that surviving patients lost to follow-up were smokers , the 6-month smoking abstinence rate was 41.5 % in the inpatient counseling with telephone follow-up group , compared with 30.2 % and 20 % in the inpatient counseling and usual care groups , respectively ( p = .05 ) . Progress to ulterior stages of change was 43.3 % , 32.1 % , and 18.2 % , respectively ( p = .02 ) . Stage of change at baseline and intervention predicted smoking status at 6 months . Discussion This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months , and progression to ulterior stages of change . The telephone follow-up was an important adjunct . It is , therefore , recommended to include such comprehensive smoking cessation programs within hospital setting s for individuals with CVD BACKGROUND The Agency for Healthcare Research and Quality ( AHRQ ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit . METHODS We conducted a r and omized , controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin ( four test sites , four control sites ) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period ( June 16 , 1999 , to June 20 , 2000 ) or the intervention period ( from June 21 , 2000 , to May 3 , 2001 ) . After collecting baseline data , staff at test sites implemented the intervention over a 2-month period . The intervention included a tutorial for intake clinicians , group and individual performance feedback for intake clinicians , use of a modified vital signs stamp , an offer of free nicotine replacement therapy , and proactive telephone counseling . Staff at control sites received only general information about the AHRQ Guideline . Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessment s. Hierarchical logistic regression models were used to estimate the odds ratios ( ORs ) for treatment assignment after adjustment for patient characteristics . All statistical tests were two-sided . RESULTS There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period . Among participants treated during the intervention period , those at test sites were more likely than those at control sites to report being abstinent at the 2-month ( 16.4 % versus 5.8 % ; adjusted OR = 3.3 , 95 % confidence interval [ CI ] = 1.9 to 5.6 ; P<.001 ) and 6-month ( 15.4 % versus 9.8 % ; adjusted OR = 1.7 , 95 % CI = 1.2 to 2.6 ; P = .009 ) follow-up assessment s and to report continuous abstinence , that is , abstinence at both 2 and 6 months ( 10.9 % versus 3.8 % ; adjusted OR = 3.4 , 95 % CI = 1.8 to 6.3 ; P<.001 ) . CONCLUSION Implementation of a guideline -based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers The purpose of this study was to examine the effectiveness of different practice -based approaches to assist patients of primary care physicians to quit smoking and sustain cessation . Forty-four nonsmoking general practitioners volunteered for the study . After a period of training , they r and omized 923 smoking clients , unselected for motivation toward quitting , to four different intervention groups : ( i ) minimal intervention , consisting of one single counselling session and a brief h and out on quitting techniques ; ( ii ) repeated counselling including reinforcing sessions at Months 1 , 3 , 6 , and 9 ; ( iii ) repeated counselling and use of nicotine gum ; and ( iv ) repeated counselling and spirometry . Biochemically vali date d smoking status was assessed at six and 12 months after recruitment . The proportion of verified quitters at 12 months was 4.8 percent among subjects r and omized to the minimal intervention group , compared to 5.5 percent , 7.5 percent , and 6.5 percent among those r and omized to the three repeated-counselling groups . In no treatment group was the outcome significantly different from that for one-time counselling at the ( P<0.05 ) level . Lack of power , contamination , and low attendance at reinforcing sessions should be taken into account in interpreting the results Objective To compare the effects of free nicotine replacement therapy or proactive telephone counselling in addition to st and ard smoking cessation support offered through a telephone quitline . Design Parallel group , 2 × 2 factorial , r and omised controlled trial . Setting National quitline , Engl and . Participants 2591 non-pregnant smokers aged 16 or more residing in Engl and who called the quitline between February 2009 and February 2010 and agreed to set a quit date : 648 were each r and omised to st and ard support , proactive support , or proactive support with nicotine replacement therapy , and 647 were r and omised to st and ard support with nicotine replacement therapy . Interventions Two interventions were offered in addition to st and ard support : six weeks ’ nicotine replacement therapy , provided free , and proactive counselling sessions ( repeat telephone calls from , and interaction with , cessation advisors ) . Main outcome measures The primary outcome was self reported smoking cessation for six or more months after the quit date . The secondary outcome was cessation vali date d by exhaled carbon monoxide measured at six or more months . Results At six months , 17.7 % ( n=229 ) of those offered nicotine replacement therapy reported smoking cessation compared with 20.1 % ( n=261 ) not offered such therapy ( odds ratio 0.85 , 95 % confidence interval 0.70 to 1.04 ) , and 18.2 % ( n=236 ) offered proactive counselling reported smoking cessation compared with 19.6 % ( n=254 ) offered st and ard support ( 0.91 , 0.75 to 1.11 ) . Data vali date d by carbon monoxide readings changed the findings for nicotine replacement therapy only , with smoking cessation vali date d in 6.6 % ( 85/1295 ) of those offered nicotine replacement therapy compared with 9.4 % ( 122/1296 ) not offered such therapy ( 0.67 , 0.50 to 0.90 ) . Conclusions Offering free nicotine replacement therapy or additional ( proactive ) counselling to st and ard helpline support had no additional effect on smoking cessation . Trial registration Clinical Trials.gov NCT00775944 Background : Smoking , alcohol use , and depression are interrelated and highly prevalent in patients with head and neck cancer , adversely affecting quality of life and survival . Smoking , alcohol , and depression share common treatments , such as cognitive behavioral therapy and antidepressants . Consequently , we developed and tested a tailored smoking , alcohol , and depression intervention for patients with head and neck cancer . Methods : Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers . Subjects were r and omized to usual care or nurse-administered intervention consisting of cognitive behavioral therapy and medications . Data collected included smoking , alcohol use , and depressive symptoms at baseline and at 6 months . Results : The mean age was 57 years . Most participants were male ( 84 % ) and White ( 90 % ) . About half ( 52 % ) were married , 46 % had a high school education or less , and 52 % were recruited from Veterans Affairs sites . The sample was fairly evenly distributed across three major head and neck cancer sites and over half ( 61 % ) had stage III/IV cancers . Significant differences in 6-month smoking cessation rates were noted with 47 % quitting in the intervention compared with 31 % in usual care ( P < 0.05 ) . Alcohol and depression rates improved in both groups , with no significant differences in 6-month depression and alcohol outcomes . Conclusion : Treating comorbid smoking , problem drinking , and depression may increase smoking cessation rates above that of usual care and may be more practical than treating these disorders separately . ( Cancer Epidemiol Biomarkers Prev 2006;15(11):2203–8 BACKGROUND Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than non-smokers . Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement . METHODS We did a r and omised trial in three hospitals in Denmark . 120 patients were r and omly assigned 6 - 8 weeks before scheduled surgery to either the control ( n=60 ) or smoking intervention ( 60 ) group . Smoking intervention was counselling and nicotine replacement therapy , and either smoking cessation or at least 50 % smoking reduction . An assessor , who was masked to the intervention , registered the occurrence of cardiopulmonary , renal , neurological , or surgical complications and duration of hospital admittance . The main analysis was by intention to treat . FINDINGS Eight controls and four patients from the intervention group were excluded from the final analysis because their operations were either postponed or cancelled . Thus , 52 and 56 patients , respectively , were analysed for outcome . The overall complication rate was 18 % in the smoking intervention group and 52 % in controls ( p=0.0003 ) . The most significant effects of intervention were seen for wound-related complications ( 5 % vs 31 % , p=0.001 ) , cardiovascular complications ( 0 % vs 10 % , p=0.08 ) , and secondary surgery ( 4 % vs 15 % , p=0.07 ) . The median length of stay was 11 days ( range 7 - 55 ) in the intervention group and 13 days ( 8 - 65 ) in the control group . INTERPRETATION An effective smoking intervention programme 6 - 8 weeks before surgery reduces postoperative morbidity , and we recommend , on the basis of our results , this programme be adopted OBJECTIVES To examine the impact of knowing quitters on cessation among homeless smokers . METHODS Secondary analysis of data derived from a community-based r and omized controlled trial of 430 homeless smokers . We conducted multivariable logistic regression analysis to determine whether knowing quitters impacted the likelihood of cessation ( salivary cotinine ≤ 20 ng/ml ) at 26-week follow-up . RESULTS Multivariable logistic regression showed cessation was more likely for smokers who knew ≥ 5 quitters compared with those who knew no quitters ( Odds Ratio = 3.79 , CI = 1.17 , 12.27 , p = .008 ) , adjusting for age , education , income , and time to first cigarette in morning . CONCLUSIONS Knowing former smokers was associated with increased likelihood of achieving smoking abstinence among homeless smokers We assessed the efficacy of a comprehensive programme for stopping smoking in 210 smokers scheduled for surgery , before admission and 3 months after attending a pre‐operative clinic . Participants were r and omly allocated to receive an intervention incorporating nicotine replacement therapy for patients smoking more than 10 cigarettes per day ( ‘ dependent smokers ’ ) , or to a control group to receive usual care . Dependent smokers allocated to the intervention group were more likely to report abstinence before surgery than those allocated to receive usual‐care ( 63 ( 73 % ) vs. 29 ( 56 % ) , respectively ; OR 2.2 ( 95 % CI 1.0–4.8 ) ) , and 3 months after attendance ( 16 ( 18 % ) vs. 3 ( 5 % ) , respectively ; OR = 3.9 ( 95 % CI 1.0–21.7 ) Cigarette smoking is prevalent in cocaine/methamphetamine-dependent patients and associated with significant morbidity and mortality , yet , the provision of smoking cessation treatment in conjunction with substance use disorder ( SUD ) treatment is not st and ard practice . This is due , in part , to clinician concern that combining smoking cessation treatment with SUD treatment could lead to poorer SUD outcomes . The NIDA Clinical Trials Network is conducting a 10-week , two-group , r and omized trial to evaluate the impact of providing smoking cessation treatment ( SCT ) with SUD treatment as usual ( TAU ) , compared to TAU alone , in smokers who are in outpatient treatment for cocaine or methamphetamine dependence . Approximately 528 participants , recruited from 12 community treatment programs , will be r and omized into the trial . The present paper describes key design decisions made during protocol development . The trial is design ed to evaluate the relationship between cigarette smoking and stimulant use , which prior research suggests is linked , and should contribute to our underst and ing of how best to address the co-occurring problems of nicotine dependence and cocaine/methamphetamine-dependence . Unique aspects of the trial include the primary question of interest , which concerns the impact of providing SCT on SUD outcomes rather than on smoking outcomes , and the intensity of the SCT chosen , which includes bupropion , nicotine replacement , and two psychosocial interventions Clients in substance abuse treatment are at high risk for smoking-related illness due to higher rates and heavier smoking than the general population . Three myths widely held by both treatment staff and substance abusers in treatment-people in treatment do not want to quit smoking , people in treatment will relapse to other drug use if they attempt to quit smoking , and people in treatment are unable to quit smoking-make it difficult to broach the matter of smoking cessation . A 16-week , cognitive-behavioral group program with nicotine patches was conducted at Oregon 's largest , private , nonprofit substance abuse treatment agency . Of 490 clients , approximately 85 % of whom smoke , 106 ( 25 % of the smokers ) were interested enough in quitting to attend an orientation . Approximately 40 % of these were methadone maintenance clients . The others were distributed among two residential and two outpatient drug-free treatment services . Of 90 assigned , 68 began voluntary treatment , and 21 were assigned to delayed treatment . Of the 66 smokers who began , 74 % succeeded in quitting smoking for at least 1 day , and 23 % were abstinent for at least 4 continuous weeks . At the end of the 16-week treatment , 7 subjects ( 11 % ) were abstinent . No control subjects quit smoking on their own . The article discusses issues of institutionalizing smoking cessation services in drug treatment agencies Background : There is insufficient and conflicting evidence about whether more intensive behavioural support is more effective than basic behavioural support for smoking cessation and whether primary care nurses can deliver effective behavioural support . Methods : A r and omised controlled trial was performed in 26 UK general practice s. 925 smokers of ⩾10 cigarettes per day were r and omly allocated to basic or weekly support . All participants were seen before quitting , telephoned around quit day , and seen 1 and 4 weeks after the initial appointment ( basic support ) . Participants receiving weekly support had an additional telephone call at 10 days and 3 weeks after the initial appointment and an additional visit at 2 weeks to motivate adherence to nicotine replacement and renew quit attempts . 15 mg/16 h nicotine patches were given to all participants . The outcome was assessed by intention to treat analyses of the percentage confirmed sustained abstinence at 4 , 12 , 26 and 52 weeks after quit day . Results : Of the 469 and 456 participants in the basic and weekly arms , the numbers ( % ) who quit and the percentage difference were 105 ( 22.4 % ) vs 102 ( 22.4 % ) , 0.1 % ( 95 % CI −5.3 % to 5.5 % ) at 4 weeks , 66 ( 14.1 % ) vs 52 ( 11.4 % ) , −2.6 % ( 95 % CI −6.9 % to 1.7 % ) at 12 weeks , 50 ( 10.7 % ) vs 40 ( 8.8 % ) , −1.9 % ( 95 % CI −5.7 % to 2.0 % ) at 26 weeks and 36 ( 7.7 % ) vs 30 ( 6.6 % ) , −1.1 % ( 95 % CI −4.4 % to 2.3 % ) at 52 weeks . Conclusions : The absolute quit rates achieved are those expected from nicotine replacement alone , implying that neither basic nor weekly support were effective . Primary care smoking cessation treatment should provide pharmacotherapy with sufficient support only to ensure it is used appropriately , and those in need of support should be referred to specialists AIM To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation material s among nicotine patch users . DESIGN Two-group r and omized controlled trial . SETTING World Wide Web in Engl and and Republic of Irel and . PARTICIPANTS A total of 3971 subjects who purchased a particular br and of nicotine patch and logged-on to use a free web-based behavioral support program . INTERVENTION Web-based tailored behavioral smoking cessation material s or web-based non-tailored material s. MEASUREMENTS Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up . FINDINGS Using three approaches to the analyses of 6- and 12-week outcomes , participants in the tailored condition reported clinical ly and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition . In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once , continuous abstinence rates at 6 weeks were 29.0 % in the tailored condition versus 23.9 % in the non-tailored condition ( OR = 1.30 ; P = 0.0006 ) ; at 12 weeks continuous abstinence rates were 22.8 % versus 18.1 % , respectively ( OR = 1.34 ; P = 0.0006 ) . Moreover , satisfaction with the program was significantly higher in the tailored than in the non-tailored condition . CONCLUSIONS The results of this study demonstrate a benefit of the web-based tailored behavioral support material s used in conjunction with nicotine replacement therapy . A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program Aims : To assess the effectiveness of a smoking cessation intervention at the workplace . The intervention was adapted to smokers ‘ tobacco dependence , and included minimal structured counselling at the first visit ( 5–8 minutes ) , nicotine patches for three months , and three sessions of counselling for reinforcement of abstinence ( 2–3 minutes ) over a three month period . Methods : Open r and omised trial with two groups : the intervention group , and the control group which was subjected to st and ard clinical practice , consisting of short ( 30 seconds to one minute ) sporadic sessions of unstructured medical antismoking advice . The trial was carried out among 217 smokers of both sexes , aged 20–63 years , motivated to quit smoking and without contraindications for nicotine patches , who were employees at a public transport company and at two worksites of an electric company . The main outcome measure was self reported tobacco abstinence confirmed by carbon monoxide in expired air ≤10 ppm . Analysis was performed according to intention-to-treat . Results : The rate of continuous abstinence at 12 months was 20.2 % for the intervention versus 8.7 % for the control group ( OR : 2.58 ; 95 % CI : 1.13 to 5.90 ; p = 0.025 ) . In subgroup analyses , effectiveness of the intervention did not vary substantially with age , tobacco dependence , number of cigarettes smoked per day , number of years of tobacco consumption , degree of desire to quit smoking , time spent with smokers , subjective health , and presence of tobacco related symptoms . Weight gain at 12 months was similar for both groups ( 1.69 kg in the intervention v 2.01 kg in the control group ; p = 0.21 ) . Conclusions : A simple and easily generalisable intervention at the workplace is effective to achieve long term smoking cessation . In a setting similar to ours , nine subjects would have to be treated for three months for one to achieve continuous abstinence for 12 months Context Although there are many health benefits for smokers who stop smoking , we still lack evidence from r and omized , controlled trials that smoking cessation programs reduce mortality . Contribution In this r and omized , controlled trial of a 10-week-long smoking cessation intervention in 5887 smokers with asymptomatic airway obstruction , 14-year mortality rates were higher in the usual care group than in the smoking cessation group ( hazard ratio , 1.18 [ 95 % CI , 1.02 to 1.37 ] ) . The mortality benefit was greatest among the 21.7 % of the intervention group who actually managed to quit smoking . Implication s Smoking cessation programs substantially reduce mortality even when only a minority of patients stop smoking . The Editors Smoking cessation almost certainly has beneficial effects on subsequent mortality ( 1 ) . However , the strongest support for this assertion comes from cohort studies , where smokers and quitters were self-selected . Results from r and omized trials , which avoid the selection issue , have largely been disappointing because mortality benefits have not been clear or have not been clearly attributable to smoking cessation ( 1 ) . The Lung Health Study ( LHS ) was a r and omized clinical trial of smoking cessation and inhaled bronchodilator ( ipratropium ) therapy in smokers 35 to 60 years of age who did not consider themselves ill but had evidence of mild to moderate airway obstruction ( 2 ) . Individuals with serious disease , hypertension , obesity , or excessive alcohol intake were excluded . The primary research questions were whether a smoking cessation program and use of inhaled ipratropium would decrease the rate of decline of lung function and would affect mortality and morbidity over 5 years . These results have been reported elsewhere ( 3 , 4 ) . The smoking cessation program was associated with cumulative reduced decline in lung function ( FEV1 ) that was largest in participants who stopped smoking early in the study ; inhaled ipratropium produced a small noncumulative increase in FEV1 that disappeared when the drug was withdrawn ( 3 ) . Intention-to-treat analysis after 5 years did not reveal differences in morbidity or mortality among treatment groups ( 4 ) , although subgroup analysis showed that smoking cessation was associated with significant reductions in fatal or nonfatal cardiovascular disease and coronary heart disease . This paper reports the effects of the study intervention on mortality in LHS participants 14.5 years after r and omization . Methods The design of the LHS has been described in detail elsewhere ( 2 ) . The participants , all volunteers , were smokers who did not consider themselves ill but had evidence of airway obstruction and little evidence of other disease . Research ers recruited participants from the community using a wide variety of techniques ( 5 ) . In 10 clinical centers , 5887 participants were r and omly assigned to 3 groups . Two special intervention groups received an intensive 10-week smoking cessation program . Briefly , the cessation intervention consisted of a strong physician message and 12 two-hour group sessions , using behavior modification and nicotine gum . Quitters entered a maintenance program that stressed coping skills . One special intervention group also received ipratropium , while the other received a placebo inhaler . A third group received usual care . About 75 % of the original participants were followed continuously for the subsequent 10 years by biannual telephone contacts and 1 clinic visit at approximately 11 to 12 years after r and omization ( 6 ) . Telephone contacts served to check smoking status , morbidity , and mortality and were not part of the intervention . All study participants provided written informed consent for the original LHS before beginning the study . The consent documents stated that smoking increases the risk for chronic obstructive pulmonary disease , respiratory tract cancer , and cardiovascular disease and that smoking cessation would decrease such risks . Additional written informed consent was obtained from persons who participated in the biannual telephone calls . Institutional review boards at each of the 10 clinical centers and the coordinating center approved the study design and consent documents . When biannual phone calls revealed a participant death , staff attempted to collect death certificates , autopsy reports , relevant medical records , and interviews with attending physicians or eyewitnesses . An independent mortality and morbidity review board examined these data and classified causes of death . In addition , a National Death Index review provided date and cause of death for all U.S. study participants through the end of 2001 . Vital status at 31 December 2001 or 14.5 years , whichever was earlier , was successfully determined for 98.3 % of all participants ; missing individuals were Canadians who had been lost to follow-up and were not accessible through the National Death Index . Mortality end points were classified in 7 categories : coronary heart disease , cardiovascular disease including coronary heart disease , lung cancer , other cancer , respiratory disease excluding lung cancer , other , and unknown . The other category included but was not limited to liver disease , kidney disease , sepsis , accidents , suicide , and AIDS . Analyses were performed on an intention-to-treat basis , comparing the special intervention group with the usual care group . The special intervention group was a combination of the groups originally assigned to receive inhaled ipratropium or placebo therapy . Both of these groups , which were very similar at baseline , received the smoking cessation program and exhibited similar rates of smoking cessation ( 3 ) . Participants were also divided into 3 groups according to smoking history during the initial 5 years of the trial . Sustained quitters were participants who stopped smoking in the first year after r and omization and maintained biochemically vali date d abstinence ( 3 ) throughout follow-up . Continuing smokers were participants who reported smoking at all follow-up visits . Intermittent quitters were participants who reported smoking at some but not all of their follow-up visits or during the time between visits . Statistical Analysis Baseline differences between the special intervention and usual care groups were tested by using t-tests for continuous variables and chi-square statistics for categorical variables . Cause-specific death rates and times to events were analyzed by using the KaplanMeier product-limit method ( 7 ) . Survival was compared among groups by using the log-rank test . Hazard ratios and adjusted analyses were obtained by using the Cox proportional hazards model . Interactions were assessed by comparing hierarchically related proportional hazards models . All P values result from 2-sided tests ; no adjustments were made for multiple comparisons . Role of the Funding Source This study was funded by a contract and grants from the National Heart , Lung , and Blood Institute of the National Institutes of Health . The funding source had a role in the design of the study and approved the manuscript before it was su bmi tted for publication . Results Baseline characteristics of LHS participants are shown in Table 1 . Most were middle-aged ; smoked heavily ; and had substantial smoking histories , airway obstruction ( FEV1FVC ratio 70 % ) , and borderline low FEV1 values . On average , participants were normotensive and had normal body mass indices . Most participants were of white ethnicity ; 37 % were women . The average participant had some post secondary education and did not drink heavily . The special intervention and usual care groups did not significantly differ at baseline , except in percentage of participants who were married , which was higher in the special intervention group ( P= 0.04 ) . Smoking status after the first 5 years differed significantly between treatment groups ( P 0.001 ) . Among special intervention participants and usual care participants , respectively , 21.7 % and 5.4 % were sustained quitters , 29.3 % and 23.3 % were intermittent quitters , and 49.0 % and 71.3 % were continuing smokers . Table 1 . Baseline Characteristics of Lung Health Study Participants There were 731 known deaths among LHS participants , as shown in Table 2 . Lung cancer was the most common cause of death ( n= 240 [ 33 % ] ) . Coronary heart disease accounted for 77 deaths ( 10.5 % ) , and cardiovascular disease including coronary heart disease accounted for 163 deaths ( 22 % ) . One hundred fifty-four participants ( 21 % ) died of cancer of organs other than the lung . Deaths due to respiratory disease other than cancer were relatively uncommon ( n= 57 [ 7.8 % ] ) . The cause of death was unknown in only 17 participants ( 2.3 % ) . Mortality did not significantly differ between the special intervention groups originally assigned to ipratropium or placebo ( Table 2 ) . Table 2 . Causes of Death by Treatment Group Figure 1 shows all-cause survival rates in the 2 treatment groups . Death rates were significantly higher in the usual care group than in the special intervention group ( 10.38 per 1000 person-years vs. 8.83 per 1000 person-years ; P= 0.03 ) . The hazard ratio for mortality in the usual care group was 1.18 ( 95 % CI , 1.02 to 1.37 ) compared with the special intervention group . Figure 2 shows categorical causes of death in the 2 treatment groups . In all categories except other , death rates were higher in the usual care group than in the special intervention group , but the difference was significant only for deaths from respiratory diseases not related to lung cancer ( 1.08 per 1000 person-years vs. 0.56 per 1000 person-years ; P= 0.01 ) . Figure 1 . All-cause 14.5-year survival . P Figure 2 . Mortality rates at 14.5 years by cause . When survival was analyzed according to smoking habit , it differed significantly between groups ( P < 0.001 ) , even after adjustment for baseline differences ( data not shown ) . Mortality was 6.04 per 1000 person-years in sustained quitters , 7.77 per 1000 person-years in intermittent quitters , and 11.09 per 1000 The aim of this study was to examine moderating and mediating factors of the efficacy of World Wide Web-based tailored behavioral smoking cessation material s. The design was a two-group r and omized controlled trial in Engl and and the Republic of Irel and . Participants were 3971 subjects who purchased a particular br and of nicotine patch and logged on to use a free Web-based behavioral support program . The intervention was Web-based tailored behavioral smoking cessation material s or Web-based nontailored material s. The 10-week continuous abstinence rate was assessed by Internet-based survey at 12-week follow-up . Potential treatment moderators were examined using subgroups of established or possible predictors of smoking cessation . Treatment mediators examined included 6-week follow-up measures of program relevance and amount of the Web-based material s read . Within all subgroups examined , subjects in the Web-based tailored intervention were more likely to report 10-week continuous abstinence at 12-week follow-up . Significant moderators , indicating a significant difference in program efficacy between subgroups , included presence of a tobacco-related illness ( larger treatment-control differences among subjects with a tobacco-related illness ) , presence of nonsmoking children in the household ( larger treatment-control differences among subjects with nonsmoking children in the household ) , and frequent alcohol consumption ( larger treatment-control differences among subjects with higher alcohol consumption ) . Perceived program relevance at 6-week follow-up was a mediator of cessation at 12-week follow-up . Robust results of the tailored program may be explained by the tailoring strategies utilized in the treatment conditions . Moderating variables may be particularly useful to address in tailored messaging . The mediating factor of perceived message relevance may provide a partial mechanism of effective program tailoring BACKGROUND We previously documented that cognitive behavioral therapy for smoking-related weight concerns ( CONCERNS ) improves cessation rates . However , the efficacy of combining CONCERNS with cessation medication is unknown . We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers . METHODS In a r and omized , double-blind , placebo-controlled trial , weight-concerned women ( n = 349 ; 86 % white ) received smoking cessation counseling and were r and omized to 1 of 2 adjunctive counseling components : CONCERNS or ST AND ARD ( st and ard cessation treatment with added discussion of smoking topics but no specific weight focus ) , and 1 of 2 medication conditions : bupropion hydrochloride sustained release ( B ) or placebo ( P ) for 6 months . Rates and duration of biochemically verified prolonged abstinence were the primary outcomes . Point-prevalent abstinence , postcessation weight gain , and changes in nicotine withdrawal , depressive symptoms , and weight concerns were evaluated . RESULTS Women in the CONCERNS + B group had higher rates of abstinence ( 34.0 % ) and longer time to relapse than did those in the ST AND ARD + B ( 21 % ; P = .05 ) or CONCERNS + P ( 11.5 % ; P = .005 ) groups at 6 months , although rates of prolonged abstinence in the CONCERNS + B and ST AND ARD + B groups did not differ significantly at 12 months . Abstinence rates and duration did not differ in the ST AND ARD + B group ( 21 % and 19 % ) compared with the ST AND ARD + P group ( 10 % and 7 % ) at 6 and 12 months , respectively . There were no differences among abstinent women in postcessation weight gain or weight concerns , although ST AND ARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did ST AND ARD + P. CONCLUSIONS Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence . This effect was not related to differences in postcessation weight gain or changes in weight concerns . Trial Registration clinical trials.gov Identifier : NCT00006170 It is known that smokers constitute an important risk group of patients undergoing surgery . It is unknown how smoking cessation intervention initiated 4 weeks prior to elective surgery affects the probability of permanent cessation . We r and omly assigned 117 patients , scheduled to undergo elective orthopaedic and general surgery , to smoking cessation intervention and control group . The intervention group underwent a programme initiated , on average , 4 weeks prior to surgery with weekly meetings or telephone counselling and were provided with free nicotine replacement therapy ( NRT ) . The control group received st and ard care . As a result , 20/55 ( 36 % ) patients the intervention group vs 1/62 ( 2 % ) in the control group became completely abstinent throughout the peri‐operative period ( p < 0.001 ) . After 1 year , those in the intervention group was most likely to be abstinent ( 18/55 ( 33 % ) vs 9/62 ( 15 % ) of the controls ( p = 0.03 ) . Level of nicotine dependence and obesity seemed to be a predictor of long‐term abstinence ( p = 0.02 ) This paper describes ( 1 ) the design , methods and baseline data of the first smoking cessation clinical trial for Chinese Americans with medical conditions - Chinese Community Smoking Cessation Project ( CCSCP ) ; ( 2 ) the collaborative process between research ers and the Chinese community ; and ( 3 ) the barriers and facilitators of implementing the study . CCSCP was a culturally tailored , r and omized , smoking cessation trial testing the efficacy of an intensive ( physician advice , in-person counseling with nicotine replacement therapy , 5 telephone calls ) compared to a minimal ( physician advice and self-help manual ) intervention . The study applied a community-sensitive research method involving community members in all phases of the research process in San Francisco Bay Area during 2001–2007 . CCSCP recruited 464 smokers from health care facilities ( 79 % ) located in Chinese neighborhoods and through Chinese language media ( 21 % ) . Baseline assessment s and interventions were conducted in-person using translated and tested question naire and intervention material s. The majority of the participants were men ( 91 % ) with a mean age of 58.3 years , foreign born ( 98 % ) , with less than high school education ( 58 % ) , spoke no English ( 42 % ) and in non-skilled or semi-skilled occupations ( 60 % ) with < $ 20,000 household income ( 51 % ) . Participants smoked regularly on an average 38.6 ± 17 years , smoked 9.1 ± 8 cigarettes per day and 85 % smoked daily . Cultural tailoring of recruitment methods and intervention design led to successful enrollment and retention of participants , overcoming barriers faced by the participants . Community sensitive collaborative process facilitated implementation of study protocol in community health care setting AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed We assessed the impact of three conditions on one-year smoking cessation rates . Physicians in 70 community general practice s were r and omly allocated by practice to one of three groups : In the usual care group , smoking patients were to receive the care they normally would receive . In the gum only group , physicians were asked to speak to patients about smoking cessation and offer nicotine gum . In the gum plus group , physicians were trained in the experimental intervention . This intervention involved advice to stop smoking , the setting of a quit date , the offer of nicotine gum , and four follow-up visits . Smoking cessation was measured by self-report after one year and vali date d using saliva cotinine measures . Using a criterion of at least three months of abstinence , 8.8 % of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4 % and 6.1 % of the patients in the usual care and gum only groups , respectively BACKGROUND Several cardiovascular disease ( CVD ) biomarkers sensitive to tobacco exposure have been identified , but how tobacco use cessation impacts them is less clear . We sought to investigate the effects of a smoking cessation program with an exercise intervention on CVD biomarkers in sedentary women . METHODS This is a cohort study on a sub sample of a 2 × 2 factorial r and omized controlled trial ( RCT ) ( exercise setting : home vs. facility ; level of exercise counseling : prescription only vs. prescription and adherence counseling ) conducted January 2004 through December 2007 . The analyses were completed in October 2010 . In the greater Boston area , 130 sedentary female smokers aged 19 - 55 completed a 15-week program . All participants received nicotine replacement therapy ( transdermal patch ) and brief behavioral counseling for 12 weeks . They all received an exercise prescription on a moderate intensity level . All exercise interventions lasted for 15 weeks , from 3 weeks precessation until 12 weeks postcessation . Main outcome measures were selected CVD biomarkers hypothesized to be affected by smoking cessation or exercise measured at baseline and 12 weeks postcessation . RESULTS Independent of tobacco abstinence , improvement was seen in inflammation ( white blood cells [ WBC ] ) , prothrombotic factor ( red blood cells [ RBC ] ) , and cardiovascular fitness level ( maximum oxygen consumption [ Vo(2)max ] ) . This suggests that even if complete abstinence is not achieved , reduction in tobacco exposure and increase in exercise can improve the cardiovascular risk profile . A significant decrease was seen for total cholesterol and the total cholesterol high-density lipoprotein cholesterol ( HDL-C ) : ratio only among the abstainers . The heart rate was reduced among all participants , but this decrease was more profound among abstainers . A significant weight gain and body mass index ( BMI ) increase were observed among abstainers and those who relapsed . We also found an increase in hemoglobin A1c ( Hb A1c ) , although significant only when the groups were combined . CONCLUSIONS A smoking cessation intervention including exercise reduced tobacco-induced cardiovascular damage selectively within 3 months This article examines reported symptoms , nonsmoking rates , and medication use among 1,018 smokers using varenicline in a r and omized trial comparing three forms of behavioral support for smoking cessation ( phone , Web , or phone + Web ) . One month after beginning varenicline , 168 people ( 17 % ) had discontinued the medication . Most ( 53 % ) quit due to side effects and other symptoms . The most common side effect among all users was nausea ( reported by 57 % of users ) . At 1 month post medication initiation , those not taking varenicline were more likely to report smoking than those who continued the medication ( 57 % vs. 16 % , p < .001 ) . Women reported more symptoms but did not discontinue medication at higher rates . Participants who received any telephone counseling ( n = 681 ) were less likely to discontinue their medication than those with Web support only ( 15 % vs. 21 % , p < .01 ) . Counseling may improve tolerance of this medication and reduce the rate of discontinuation due to side effects PURPOSE Smoking cessation is an important goal for smokers with coronary artery disease ( CAD ) because it reduces cardiac morbidity and mortality . Effective interventions for cigarette smokers with CAD exist , but they often are considered to be intensive and expensive . Stepped-care interventions have been proposed as a promising way to allocate smoking cessation treatments in a cost-effective manner . Stepped care refers to the practice of initiating treatment with low-intensity intervention and then exposing treatment failures to successively more intense interventions . METHODS To address the efficacy of this approach , 254 cigarette smokers hospitalized with CAD were provided a brief cessation intervention . The participants then were assigned r and omly to either a more intensive stepped-care treatment ( counseling and nicotine patch therapy ) or no additional treatment . Outcomes were point-prevalent abstinence measured 3 months and 1 year after hospital discharge . RESULTS Stepped-care treatment increased smoking cessation rates from 42 % to 53 % during a 3-month follow-up period ( P = .05 ) , but showed little effect at the 1-year follow-up assessment , as evidence d by a cessation rate for the minimal intervention group of 36 % versus 39 % for the stepped-care group ( P = .36 ) . CONCLUSIONS A stepped-care approach to smoking cessation increased short-but not long-term point-prevalent abstinence in patients with CAD . For improvement of long-term effectiveness , refinement of the timing and content of stepped-care interventions needs to occur 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 Objective : To assess the relative impacts of three physician-delivered smoking interventions in combination with follow-up contact from behavioral counselors . Design : R and omized controlled trial with pre-post measures of smoking rates . This paper reports six-month outcome data . Setting : Participants were recruited from among patients seen by 196 medical and family practice residents in five primary care clinics . Participants : Participants were 1,286 patients out of 1,946 eligible smokers approached . The patient group was 57 % female and 91 % white , had an average age of 35 years , and smoked , on average , slightly over one pack per day . Intervention : Physicians were trained to provide each of three interventions : advice only , brief patient-centered counseling , and counseling plus prescription of nicotine-containing gum ( Nicorette ™ ) . Half the patients received follow-up in the form of telephone counseling at three-monthly intervals from behavioral counselors . Measurements and main results : Changes in smoking behaviors were assessed by telephone interview six months after physician intervention . The differences in one-week point prevalence cessation rates among the physician interventions were significant ( p<0.01 ) : advice only , 9.1 % ; counseling , 11.9 % ; counseling plus gum , 17.4 % ; with no effect for telephone counseling . The time elapsed from physician encounter to initial quitting and the length of that period of abstinence also showed significant benefit of the counseling interventions . Patients receiving physician counseling were much more likely than those not receiving counseling to rate their physician as very helpful ( p<0.001 ) . Multiple regression analyses are also reported . Conclusion : Smoking intervention counseling provided by physicians is well received by patients and significantly increases the likelihood of cessation at six months , an effect that is augmented by the prescription of nicotine-containing gum , when compared with physician-delivered advice . Follow-up telephone counseling does not contribute significantly to smoking behavior changes INTRODUCTION Smoking prevalence in homeless population s is strikingly high ( ∼70 % ) ; yet , little is known about effective smoking cessation interventions for this population . We conducted a community-based clinical trial , Power To Quit ( PTQ ) , to assess the effects of motivational interviewing ( MI ) and nicotine patch ( nicotine replacement therapy [ NRT ] ) on smoking cessation among homeless smokers . This paper describes the smoking characteristics and comorbidities of smokers in the study . METHODS Four hundred and thirty homeless adult smokers were r and omized to either the intervention arm ( NRT + MI ) or the control arm ( NRT + Brief Advice ) . Baseline assessment included demographic information , shelter status , smoking history , motivation to quit smoking , alcohol/other substance abuse , and psychiatric comorbidities . RESULTS Of the 849 individuals who completed the eligibility survey , 578 ( 68.1 % ) were eligible and 430 ( 74.4 % of eligibles ) were enrolled . Participants were predominantly Black , male , and had mean age of 44.4 years ( S D = 9.9 ) , and the majority were unemployed ( 90.5 % ) . Most participants reported sleeping in emergency shelters ; nearly half had been homeless for more than a year . Nearly all the participants were daily smokers who smoked an average of 20 cigarettes/day . Nearly 40 % had patient health question naire-9 depression scores in the moderate or worse range , and more than 80 % screened positive for lifetime history of drug abuse or dependence . CONCLUSIONS This study demonstrates the feasibility of enrolling a diverse sample of homeless smokers into a smoking cessation clinical trial . The uniqueness of the study sample enables investigators to examine the influence of nicotine dependence as well as psychiatric and substance abuse comorbidities on smoking cessation outcomes OBJECTIVES We evaluated smoking-cessation efficacy of an extended course of sustained-release bupropion ( bupropion SR ) and cognitive-behavioral treatment ( CBT ) . METHODS Participants who smoked at least 10 cigarettes per day and who smoked within 30 minutes of arising ( n = 406 ) completed a 12-week smoking-cessation treatment including group counseling , nicotine-replacement therapy , and bupropion SR . Participants were then r and omly assigned to 1 of 5 conditions : ( 1 ) no further treatment , ( 2 ) active bupropion SR for 40 weeks , ( 3 ) placebo for 40 weeks , ( 4 ) active bupropion SR and 11 sessions of CBT for 40 weeks ( A-CBT ) , or ( 5 ) placebo and 11 sessions of CBT for 40 weeks . Participants were assessed at baseline and at weeks 12 , 24 , 52 , 64 , and 104 . RESULTS A-CBT was not superior to the other 3 extended treatments . From weeks 12 through 104 , all extended treatment conditions were superior to st and ard treatment . At weeks 64 and 104 , the 2 CBT conditions produced significantly higher abstinence rates than did the other 3 conditions . CONCLUSIONS Brief contact with providers can increase abstinence during treatment . CBT may increase long-term abstinence after extended treatment is terminated Alcohol dependent smokers ( N=118 ) enrolled in an intensive outpatient substance abuse treatment program were r and omized to a concurrent brief or intensive smoking cessation intervention . Brief treatment consisted of a 15-min counseling session with 5 min of follow-up . Intensive intervention consisted of three 1-hr counseling sessions plus 8 weeks of nicotine patch therapy . The cigarette abstinence rate , verified by breath carbon monoxide , was significantly higher for the intensive treatment group ( 27.5 % ) versus the rate for the brief treatment group ( 6.6 % ) at 1 month after the quit date but not at 6 months , when abstinence rates fell to 9.1 % for the intensive treatment group and 2.1 % for the brief treatment group . Smoking treatment assignment did not significantly impact alcohol outcomes . Although intensive smoking treatment was associated with higher rates of short-term tobacco abstinence , other , perhaps more intensive , smoking interventions are needed to produce lasting smoking cessation in alcohol dependent smokers AIMS This study used Ecological Momentary Assessment ( EMA ) data from smokers trying to quit to assess relations among coping , positive affect , negative affect and smoking . The effects of stress coping on affect and smoking were examined . DESIGN Data from a r and omized clinical trial of smoking cessation treatments were su bmi tted to multi-level modeling to test the effects of coping with stressful events on subsequent affect and smoking . SETTING Center for Tobacco Research and Intervention , Madison , Wisconsin . PARTICIPANTS A total of 372 adult daily smokers who reported at least one stressful event and coping episode and provided post-quit data . MEASUREMENTS Participants ' smoking , coping and affect were assessed in near real time with multiple EMA reports using electronic diaries pre- and post-quit . FINDINGS Multi-level models indicated that a single coping episode did not predict a change in smoking risk over the next 4 or 48 hours , but coping in men was associated with concurrent reports of increased smoking . Coping predicted improved positive and negative affect reported within 4 hours of coping , but these affective gains did not predict reduced likelihood of later smoking . Pre-quit coping frequency and gender moderated post-quit stress coping relations with later positive affect . Men and those with greater pre-quit coping frequency reported greater gains in positive affect following post-quit coping . CONCLUSIONS Coping responses early in a quit attempt may help smokers trying to quit feel better , but may not help them stay smoke-free Abstract OBJECTIVE : To examine the predictors of quitting among African American ( AA ) light smokers ( < 10 cigarettes per day ) enrolled in a smoking cessation trial . METHODS : Baseline variables were analyzed as potential predictors from a 2 × 2 cessation trial in which participants were r and omly assigned to 1 of 4 treatment groups : nicotine gum plus health education ( HE ) counseling , nicotine gum plus motivational interviewing ( MI ) counseling , placebo gum plus HE counseling , or placebo gum plus MI counseling . Chi-square tests , 2 sample t-tests , and multiple logistic regression analyses were used to identify predictors of cotinine ( COT ) verified abstinence at month 6 . RESULTS : In the final regression model , HE rather than MI counseling ( odds ratio [OR]=2.26 % , 95 % confidence interval [CI]=1.36 to 3.74 ) , older age ( OR=1.03 % , 95 % CI=1.01 to 1.06 ) , and higher body mass index ( OR=1.04 % , 95 % CI=1.01 to 1.07 ) significantly increased the likelihood of quitting , while female gender ( OR=0.46 % , 95 % CI=0.28 to 0.76 ) , ≤$1,800/month income ( OR=0.60 % , 95 % CI=0.37 to 0.97 ) , higher baseline COT ( OR=0.948 % , 95 % CI=0.946 to 0.950 ) , and not completing all counseling sessions ( OR=0.48 % , 95 % CI=0.27 to 0.84 ) reduced the odds of quitting . CONCLUSIONS : Individual characteristics may decrease the likelihood of quitting ; however , the provision of directive , advice-oriented counseling focused on the addictive nature of nicotine , health consequences of smoking , benefits of quitting , and development of a concrete quit plan may be an important and effective facilitator of quitting among AA light smokers OBJECTIVE We report on the process evaluation of an efficacious national smoking cessation intervention for adult survivors of childhood cancer . We examine associations between intervention implementation characteristics and study outcomes , as well as participant characteristics related to level of involvement in the intervention . METHODS The study was conducted at the Dana-Farber Cancer Institute in Boston , Massachusetts , from 1999 - 2001 . Participants ( n = 398 ) were r and omly assigned to receive a proactive telephone-based peer counseling intervention . They received up to 6 counseling calls , individually tailored and survivor-targeted material s , and nicotine replacement therapy ( NRT ) patches if they were prepared to quit smoking . RESULTS Forty-two percent of survivors participated in the maximum number of calls ( 5 - 6 ) , and 29 % of participants requested and received NRT . Total counseling time was an average of 51 min . Quit status at follow-up was related to intervention dose , and participants who received NRT were significantly more likely to make a 24-h quit attempt . Demographic variables ( females , White ) , higher daily smoking rate , poorer perceived health and moderate perceived risk of smoking were significantly related to greater intervention involvement . CONCLUSIONS A brief peer-delivered , telephone counseling intervention is an effective way to intervene with adult survivors of childhood cancer who are smoking . Findings from the process evaluation data ( call length and number , frequency , and spacing ) will inform future telephone counseling cessation programs OBJECTIVE To compare the efficacy and safety of 22-mg and 44-mg doses of transdermal nicotine therapy when it is paired with minimal , individual , or group counseling to improve smoking cessation rates . DESIGN An 8-week clinical trial ( 4 weeks double-blind followed by 4 weeks open label ) using r and om assignment of participants to both dose ( 22 or 44 mg ) and counseling ( minimal , individual , or group ) conditions . PARTICIPANTS Daily cigarette smokers ( > or = 15 cigarettes per day for at least 1 year ) who volunteered to participate in a study of smoking cessation treatment . A total of 504 participants were enrolled at two sites . INTERVENTION Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction ( 2 weeks of 22 mg followed by 2 weeks of 11 mg ) . Counseling consisted of a self-help pamphlet ( minimal ) ; a self-help pamphlet , a brief physician motivational message , and three brief ( < 15 minutes ) follow-up visits with a nurse ( individual ) ; or the pamphlet , the motivational message , and eight weekly 1-hour group smoking cessation counseling visits ( group ) . All participants returned weekly to turn in question naires and for assessment of their smoking status . MAIN OUTCOME MEASURES Abstinence from smoking was based on self-report , confirmed by an expired carbon monoxide concentration lower than 10 ppm . Withdrawal severity was assessed by means of an eight-item self-report question naire completed daily . RESULTS Smoking cessation rates for the two nicotine patch doses and three levels of counseling did not differ significantly at either 8 weeks or 26 weeks following the quit date . Among those receiving minimal contact , the 44-mg dose produced greater abstinence at 4 weeks than did the 22-mg dose ( 68 % vs 45 % ; P < .01 ) . Participants receiving minimal-contact adjuvant treatment were less likely to be abstinent at the end of 4 weeks than those receiving individual or group counseling ( 56 % vs 67 % ; P < .05 ) . The 44-mg dose decreased desire to smoke more than the 22-mg dose , but this effect was not related to success in quitting smoking . Transdermal nicotine therapy at doses of 44 mg produced a significantly greater frequency of nausea ( 28 % ) , vomiting ( 10 % ) , and erythema with edema at the patch site ( 30 % ) than did a 22-mg dose ( 10 % , 2 % , and 13 % , respectively ; P < .01 for each adverse effect ) . Three serious adverse events occurred during use of the 44-mg patch dose . CONCLUSIONS There does not appear to be any general , sustained benefit of initiating transdermal nicotine therapy with a 44-mg patch dose or of providing intense adjuvant smoking cessation treatment . The two doses and all adjuvant treatments produced equivalent effects at the 26-week follow-up , and the higher patch dose produced more adverse effects . Higher-dose ( 44-mg ) nicotine replacement does not appear to be indicated for general clinical population s , although it may provide short-term benefit to some smokers attempting to quit with minimal adjuvant treatment Whereas telephone-based counseling has been found to be effective in supporting smokers interested in quitting smoking , it is not known whether proactive efforts to reach smokers receiving cessation medications will enhance their likelihood of successful quitting . We had an opportunity to test , in a health plan setting , an offer of telephone-based counseling with smokers identified from health plan records as recently filling a prescription for nicotine replacement therapy or bupropion . After we removed 31 members determined to be ineligible , 1,329 were r and omly allocated to receive an invitation either to telephone-based counseling ( n = 663 ) or to a control group ( n = 666 ) . On average , 7 days ( range = 3 - 15 days ) elapsed from the day of the prescription fill until the Center for Health Promotion began calling to invite members to participate in telephone counseling . The Center for Health Promotion was able to reach 49 % of those in the intervention group ( 323/663 ) . Of these members , 118 ( 37 % ) declined any participation . Therefore , in response to the proactive contact , 63 % ( 205/323 ) of those reached and 31 % ( 205/663 ) of those eligible participated in some smoking cessation counseling . At the 3-month follow-up , we observed an increased quit rate ( 33.1 % vs. 27.4 % ) among health plan members r and omized to telephone-based smoking cessation counseling . The results varied by gender and amount smoked . In addition , the variables associated with quitting in a multivariate logistic regression model included older age and using more than 30 days of medication BACKGROUND Smoking remains the primary preventable cause of death and illness in the U.S. Effective , convenient treatment programs are needed to reduce smoking prevalence . PURPOSE This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline . METHODS Current treatment-seeking smokers ( n=1202 ) were recruited from a large healthcare organization between October 2006 and October 2007 . Eligible participants were r and omized to one of three smoking-cessation interventions : web-based counseling ( n=401 ) ; proactive telephone-based counseling ( PTC ; n=402 ) ; or combined PTC and web counseling ( n=399 ) . All participants received a st and ard 12-week FDA -approved course of varenicline . Self-report determined the primary outcomes ( 7-day point prevalent abstinence at 3- and 6-month follow-ups ) ; the number of days varenicline was taken ; and treatment-related symptoms . Behavioral measures determined utilization of both the web- and Phone-based counseling . RESULTS Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months ( 38.9 % , 48.5 % , 43.4 % ) and at 6 months ( 30.7 % , 34.3 % , 33.8 % ) for the web , PTC , and PTC-web groups , respectively . The PTC group had a significantly higher percentage of abstinence than the web group at 3 months ( OR=1.48 , 95 % CI=1.12 , 1.96 ) , but no between-group differences in abstinence outcomes were seen at 6 months . CONCLUSIONS Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence , but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline AIM Approximately 50 % of African American smokers are light smokers ( smoke < or = 10 cigarettes a day ) . The prevalence of light smoking in the United States is increasing , yet there has not been a single smoking cessation clinical trial targeting light smokers . The purpose of this 2 x 2 factorial , r and omized clinical trial was to evaluate the efficacy of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) for African American light smokers . DESIGN Participants were assigned r and omly to one of four study arms : 2 mg nicotine gum plus health education ( HE ) ; 2 mg nicotine gum plus motivational interviewing ( MI ) ; placebo gum plus HE ; and placebo gum plus MI . PARTICIPANTS AND SETTING A total of 755 African American light smokers ( 66 % female , mean age = 45 ) were enrolled at a community health center over a 16-month period . INTERVENTION AND MEASUREMENTS Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study . Biochemical measures included expired carbon monoxide ( CO ) and serum and salivary cotinine . FINDINGS Seven-day quit rates for nicotine gum were no better than for the placebo group ( 14.2 % versus 11.1 % , P = 0.232 ) at 6 months . However , a counseling effect emerged , with HE performing significantly better than MI ( 16.7 % versus 8.5 % , P < 0.001 ) . These results were consistent across outcome time-points ( weeks 1 , 8 , and 26 ) . CONCLUSIONS Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation . Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit Pharmacists may be effective health care practitioners to deliver smoking cessation interventions . This paper examines the short-term outcomes of smokers r and omized to one of two models of a pharmacist-led smoking cessation intervention . Methods : An open-label pragmatic r and omized trial compared two models of a pharmacist-led behavioral intervention [ Group A ( 3-sessions ) vs. Group B ( 1-session ) ] in conjunction with 5 weeks of nicotine replacement therapy ( NRT ) . Ninety-eight pharmacies in Ontario , Canada delivered the intervention . Baseline demographic and smoking behavior data were recorded , as were intervention characteristics . Self-reported , 7-day point prevalence quit rates were obtained 5-week postintervention start date . Results : 6,987 individuals participated ; 51.4 % ( n = 3588 ) r and omized to Group A ; 48.6 % ( n = 3399 ) to Group B. Approximately , 50 % of Group A participants completed all three sessions . Quit rates were significantly higher among Group A , 3-session completers ( 27.7 % ; n = 478 ) compared to Group B participants ( 18.0 % ; n = 604 ) . Multivariable results suggest that even when controlling for possible confounders and clustering across pharmacies , Group A participants who completed all three sessions were more likely to quit compared to Group B [ OR = 1.72 ( 95 % CI : 1.53 , 1.94 ) ] . Conclusions : Cessation outcomes are higher among participants completing three intervention sessions compared to one session ; however , many do not return for follow-up sessions OBJECTIVE Accepted treatments for cigarette smoking rarely achieve abstinence rates of > 35 % at 1 year . Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction . Using a chronic disease model of smoking , the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment . METHOD One hundred sixty smokers of > or = 10 cigarettes/day were r and omly assigned to one of four treatment conditions in a two-by-two ( nortriptyline versus placebo by brief versus extended treatment ) design . All subjects received 8 weeks of a transdermal nicotine patch , five group counseling sessions , and active or placebo treatment . Interventions for subjects in brief treatment ended at this point . Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions , with checkup telephone calls midway through each session . Subjects were assessed at baseline and weeks 12 , 24 , 36 , and 52 . The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence . RESULTS At week 52 , point-prevalence abstinence rates with missing subjects imputed as smokers were 30 % for placebo brief treatment , 42 % for placebo extended treatment , 18 % for active brief treatment , and 50 % for active extended treatment . With missing subjects omitted , these rates were 32 % , 57 % , 21 % , and 56 % , respectively . CONCLUSIONS Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature This was the first r and omized , controlled smoking cessation trial assessing the efficacy of an exercise intervention as an adjunct to nicotine gum therapy in comparison with both equal contact control and st and ard care control conditions . Sedentary female smokers aged 18 - 55 years were provided with nicotine gum treatment along with brief behavioral counseling and were r and omized into one of these three behavioral adjunct conditions . In the " intent-to-treat " sample ( N = 182 ) , at end of treatment and at 1-year follow-up , there were clear , but nonsignificant , trends in univariate analyses in which the exercise and equal contact control conditions both had higher rates of abstinence than the st and ard care control . However , when adjusting for other predictors of relapse in a multiple logistic regression , both exercise and equal contact control showed an advantage over st and ard care control in avoiding early relapse ( i.e. , after 1 week ) . In a multivariate survival model adjusting for other predictors , the equal contact condition had a significantly lower likelihood of relapse compared with the st and ard care condition and there was a near significant trend in which exercise offered an advantage over st and ard care as well . While these findings suggest a slightly improved likelihood of abstinence with exercise compared with st and ard care , exercise did not differ from equal contact control in its efficacy . Potential explanations for these equivalent levels of efficacy and implication s for the findings are discussed AIMS Smoking cessation programs are highly cost-effective . The cost-effectiveness of programs for psychiatric patients may be affected by differences in cost , efficacy , survival and quality of life . We evaluated cost-effectiveness of a program for smokers being treated for depression . DESIGN A r and omized trial compared brief contact to a stepped smoking cessation program in 322 cigarette smoking mental health out- patients . We determined the intervention 's direct cost . Because smoking cessation may affect short-term use of mental health care , we used administrative data bases and self-report to find mental health-care cost . FINDINGS The 163 individuals r and omized to stepped care received an average of $ 346 of smoking cessation services , including $ 221 for computer-mediated assessment s of readiness to quit , and $ 124 for counseling , nicotine replacement therapy and bupropion . The cessation program was used by 53 participants . Total cost of smoking cessation and mental health services was $ 4805 in the stepped care group and $ 4173 in the brief-contact care group ( not significantly different ) . After 18 months of follow-up , the stepped care group had 5.5 % greater abstinence from smoking . Smoking cessation services cost $ 6204 per successful quit . Cessation services and mental health care cost was $ 11 496 per successful quit . CONCLUSION If smoking cessation yields 1.2 years additional life , the cessation services cost $ 5170 per life-year , and cessation services and mental health care cost $ 9580 per life-year . Even if quitting does not increase survival of depressed individuals as well as in other smokers , the stepped care intervention is likely to be regarded as cost-effective Abstract INTRODUCTION : Many smokers reduce their cigarette consumption during failed attempts to quit . We report the impact of changes in consumption on smoking-related respiratory symptom severity ( SRRSS ) . METHODS : Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a r and omized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation . Cigarette use in the 28 days prior to the interview , and severity of SRRSS using a 7-item respiratory index , were assessed at baseline and at 3-month follow-up . OUTCOME : Baseline minus 3-month assessment difference in SRRSS score . RESULTS : Follow-up of 319 participants ( 83.3 % ) , mean age 40.4 years , 51.4 % male , who smoked 26.4 cigarettes per day , demonstrated a mean reduction of 16.7 cigarettes per day . A reduction in cigarette use was positively and significantly ( b=0.29 , t=5.16 , P<.001 ) associated with a reduction in smoking-related symptom severity after adjusting for age , gender , race , years of regular smoking , baseline nicotine dependence , and history of treatment for asthma or emphysema . A 1 st and ard deviation reduction in average daily smoking ( about 14.1 cigarettes ) was associated with a 0.28 st and ard deviation decrease in smoking-related symptom severity . CONCLUSION : Reduction in symptom severity increases as absolute reduction in daily smoking increases . This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking Objective To estimate the “ real-world ” effectiveness of commonly used aids to smoking cessation in Engl and by using longitudinal data . Patients and Methods We conducted a prospect i ve cohort study in 1560 adult smokers who participated in an English national household survey in the period from November 2006 to March 2012 , responded to a 6-month follow-up survey , and made at least 1 quit attempt between the 2 measurements . The quitting method was classified as follows : ( 1 ) prescription medication ( nicotine replacement therapy [ NRT ] , bupropion , or varenicline ) in combination with specialist behavioral support delivered by a National Health Service Stop Smoking Service ; ( 2 ) prescription medication with brief advice ; ( 3 ) NRT bought over the counter ; ( 4 ) none of these . The primary outcome measure was self-reported abstinence up to the time of the 6-month follow-up survey , adjusted for key potential confounders including cigarette dependence . Results Compared with smokers using none of the cessation aids , the adjusted odds of remaining abstinent up to the time of the 6-month follow-up survey were 2.58 ( 95 % CI , 1.48 - 4.52 ) times higher in users of prescription medication in combination with specialist behavioral support and 1.55 ( 95 % CI , 1.11 - 2.16 ) times higher in users of prescription medication with brief advice . The use of NRT bought over the counter was associated with a lower odds of abstinence ( odds ratio , 0.68 ; 95 % CI , 0.49 - 0.94 ) . Conclusion Prescription medication offered with specialist behavioral support and that offered with minimal behavioral support are successful methods of stopping cigarette smoking in Engl and 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 AIM To test , in combination with the nicotine patch , the incremental efficacy of a maximal , tailored behavioral treatment over a minimal treatment for smoking cessation . DESIGN R and omized clinical trial with 6-month follow-up . SETTING Five methadone maintenance treatment centers in Rhode Isl and . PARTICIPANTS Three hundred and eighty-three methadone-maintained smokers . INTERVENTION Participants were assigned r and omly to nicotine patch ( 8 - 12 weeks ) plus either ( 1 ) a baseline tailored brief motivational intervention , a quit date behavioral skills counseling session and a relapse prevention follow-up session ( Max ) or ( 2 ) brief advice using the National Cancer Institute 's 4 As model ( Min ) . An intent-to-treat analysis with those lost to follow-up assumed to smoke was used . MEASUREMENTS Carbon monoxide (CO)-confirmed 7-day point smoking cessation prevalence at 3 and 6 months , and self-reported numbers of cigarettes smoked per day . FINDINGS Participants had a mean age of 40 years , were 53 % male , 78 % Caucasian , smoked 26.7 ( + /- 12.2 ) cigarettes/day and had a mean methadone dose of 95.5 mg . At 3 months , 317 ( 83 % ) were re-interviewed ; at 6 months , 312 ( 82 % ) were re-interviewed . The intent-to-treat , 7-day point prevalence estimate of cessation was 5.2 % in the Max group and 4.7 % in the Min group ( P=0.81 ) at 6 months . In logistic models with treatment condition , age , gender , race , Fagerström Test for Nicotine Dependence and cigarettes per day as covariates , males were more likely to be abstinent at 3 months ( OR 4.67 ; P=0.003 ) and 6 months ( OR 4.01 ; P=0.015 ) . CONCLUSION A tailored behavioral intervention did not increase quit rates over patch and minimal treatment . Smoking cessation rates in methadone-maintained smokers are low , with men having greater success BACKGROUND This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital in patients and to identify variables associated with long-term smoking cessation following hospitalization . METHODS One hundred eighty-five patients were r and omly assigned to one of three smoking cessation interventions : ( 1 ) A Minimal Care ( MC ) condition , consisting of a brief physician-delivered motivational message to stop smoking , ( 2 ) a Counseling + Active Nicotine Patch ( CAP ) condition in which patients received the motivational message , a 6-week supply of nicotine patches , and extended bedside and telephone counseling , and ( 3 ) a Counseling + Placebo Patch ( CPP ) condition identical to the CAP condition except the supplied patches contained no nicotine . RESULTS At 6-month follow-up , abstinence rates for the three treatments were 4.9 , 6.5 , and 9.7 % for the MC , CPP , and CAP treatments , respectively . These differences were not statistically significant . Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis . The nicotine patch was well tolerated by hospital in patients . CONCLUSIONS The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses . Our study provided no evidence of the superiority of nicotine patches versus placebo , but this does not preclude the possibility that future research using larger sample s might detect differences between patch groups . Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women . It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered . This study used a two level factorial design to examine the independent and interactive effects of medication ( bupropion 300 mg/day vs. placebo ) and psychotherapy ( cognitive-behavioral therapy [ CBT ] vs. supportive therapy [ ST ] ) . In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments , we examined medication compliance and its role in the efficacy of bupropion . Participants were 154 women , aged at least 30 years and smoking more than 10 cigarettes/day . Compliance with study medication was assessed using Medication Event Monitoring Systems ( MEMS ) over 7 weeks of treatment . Psychological interventions were delivered in 60-min weekly group sessions . Longitudinal analysis of abstinence outcomes from end of treatment ( EOT ) through 12 months after treatment revealed a significant interaction of medication and therapy . Higher abstinence rates at EOT and 3- , 6- , 9- , and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT ( 44 % , 24 % , 30 % , 23 % , 17 % ) rather than with ST ( 18 % , 1 % , 8 % , 5 % , 2 % ) . The bupropion-CBT combination , however , was not clearly superior to placebo , regardless of therapy assignment . Higher rates of medication compliance were positively predictive of abstinence , and this effect was most evident in the placebo condition . Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women We evaluated gender differences in demographic , smoking history , nicotine dependence , transtheoretical , and perceived stress variables as predictors of smoking cessation . Participants ( n = 381 ) smoked at least 15 cigarettes per day and were motivated to quit . The outcome variable was 7-day abstinence at 1-year follow-up . Predictor variables included : age , education level , number of years smoking , cigarettes per day , quit attempts , nicotine dependence , stage of change , decisional balance , processes of change , self-efficacy , and perceived stress . Logistic regression analysis was used to derive predictive models for women and men . In women , lower scores for pre- and mid-treatment perceived stress significantly increased the likelihood of being abstinent at follow-up . For men , a higher level of education or number of quit attempts lasting > 24 hours in the past year , along with less frequent use of behavioural processes of change at baseline increased the probability of being abstinent at follow-up A total of 205 ( 113 male , 92 female ) nonhospitalized recovering alcoholics with > 3 months of continuous abstinence from alcohol and drugs and relatively heavy tobacco dependence ( Fagerstrom Tolerance Question naire score = 7.7 ; mean number of cigarettes per day , 26.8 ; mean number of years smoked , 24.4 ) were r and omized to st and ard treatment ( ST ) American Lung Association quit program plus nicotine anonymous meetings ( n = 70 ) , behavioral counseling plus physical exercise ( BEX ; n = 72 ) , or behavioral counseling plus nicotine gum ( BNIC ; n = 63 ) . A 3 x 4 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline , posttreatment , and 6- and 12-month follow-ups . Self-reported smoking status was verified with biochemical and informant report . Verified self-report indicated that significantly more smokers in BEX quit by posttreatment ( 60 % ) than in either BNIC ( 52 % ) or ST ( 31 % ) , chi 2 ( 2 , N = 205 ) = 17.85 , p < .01 , but not at the 6-month ( 29 % , 27 % , and 21 % , respectively ) or 12-month ( 27 % , 27 % , and 26 % , respectively ) follow-up . Only 4 % ( 7 of 188 ) relapsed to alcohol or drugs . Alcohol relapse did not differ by treatment group or smoking status . Length of alcohol abstinence was not associated with smoking cessation outcome Background Smokers have a higher risk of complicated tissue and wound healing after surgery than nonsmokers . We tested the hypothesis that short‐term pre‐operative cessation of smoking in colorectal surgery decreases the incidence of postoperative tissue and wound complications Despite high rates of smoking among people with psychotic disorders , and the associated health and financial burden , few studies have investigated the characteristics of this group of smokers . This paper reports data from 298 smokers with an ICD-10 psychotic disorder residing in the community ( 56.7 % with schizophrenia or schizoaffective disorder ) , including an examination of their demographic and clinical characteristics , smoking behaviours , severity of nicotine dependence , stage of change , and reasons for smoking and for quitting . St and ardized self-report instruments were used , in conjunction with structured interviews , as part of the first phase of a r and omized controlled trial . On average , participants smoked 30 cigarettes per day , commenced smoking daily at about 18 years of age ( 5 years before illness onset ) , and had made 2 - 3 quit attempts in their lifetime . Higher levels of nicotine dependence and concurrent hazardous use of alcohol or cannabis were associated with a younger age at smoking initiation . The present sample was also more likely to report stress reduction , stimulation and addiction as reasons for smoking , compared to a general sample of smokers . Males , precontemplators and participants with concurrent hazardous substance use cited fewer reasons for quitting smoking . These and other subgroup differences in smoking characteristics are used to illustrate potential implication s for the nature and timing of smoking interventions among people with a psychotic disorder BACKGROUND A history of major depressive disorder ( MDD ) predicts failure to quit smoking . We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD . The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence . METHODS This was a 2 ( nortriptyline vs placebo ) x 2 ( cognitive-behavioral therapy vs control ) x 2 ( history of MDD vs no history ) r and omized trial . The participants were 199 cigarette smokers . The outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 38 , and 64 . Mood , withdrawal , and depression were measured at 3 , 5 , and 8 days after the smoking quit date . RESULTS Nortriptyline produced higher abstinence rates than placebo , independent of depression history . Cognitive-behavioral therapy was more effective for participants with a history of depression . Nortriptyline alleviated a negative affect occurring after smoking cessation . Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessment s for MDD history-negative smokers . There was also a sex-by-depression history interaction ; MDD history-positive women were less likely to be abstinent than MDD history-negative women , but depression history did not predict abstinence for men . CONCLUSIONS Nortriptyline is a promising adjunct for smoking cessation . Smokers with a history of depression are aided by more intensive psychosocial treatments . Mood and diagnosis interact to predict relapse . Increases in negative affect after quitting smoking are attenuated by nortriptyline A hospitalization is a time when perceived vulnerability to dangers from smoking and quitting motivation may be at their peak . Aim was to determine whether a smoking cessation intervention of moderate intensity would increase the smoking cessation rate in hospitalized smokers . Design was r and omized trial , conducted in a university-affiliated cardio-pulmonary tertiary care center . Participants were hospitalized smokers aged < or = 70 years . Intervention was a smoking cessation intervention consisting of education and psychological support , with or without pharmacological therapy , associated with follow-up phone calls . Patients assigned to the control group received usual care . Measurement was point prevalence cessation rate at 1-year follow-up . A total of 468 patients were screened ; 196 were r and omized . Although the smoking cessation rates at 12-month follow-up were higher than expected , we found no significant difference between the study groups ( intervention : 30.3 % ; control : 27.8 % ) . Similar results were obtained in patients whose smoking status was vali date d by urinary cotinine assay . Length of stay and dependence to nicotine were the only significant predictors of smoking cessation . A smoking cessation intervention of moderate intensity delivered in a tertiary cardio-pulmonary center did not increase the smoking cessation rate at 1-year follow-up . The results of this trial should not divert those who deliver care to in patients from delivering a brief smoking cessation intervention Earlier research indicated that a 10-session mood management ( MM ) intervention was more effective than a 5-session st and ard intervention for smokers with a history of major depressive disorder ( MDD ) . In a 2 x 2 factorial design , the present study compared MM intervention to a contact-equivalent health education intervention ( HE ) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD . Participants were 201 smokers , 22 % with a history of MDD . Contrary to the earlier findings , the MM and HE interventions produced similar abstinence rates : 2 mg gum was no more effective than placebo . History-positive participants had a greater increase in mood disturbance after the quit attempt . Independent of depression diagnosis , increases in negative mood immediately after quitting predicted smoking . No treatment differences were found in trends over time for measures of mood , withdrawal symptoms , pleasant activities and events , self-efficacy , and optimism and pessimism . History-positive smokers may be best treated by interventions providing additional support and contact , independent of therapeutic content OBJECTIVES The aims of this study were to identify prospect i ve determinants of smoking cessation in COPD patients , and to assess whether prospect i ve determinants vary between two different cessation interventions . METHODS Two hundred and twenty-five moderate to severe COPD patients were r and omly allocated to two smoking cessation interventions . One-year cotinine-vali date d continuous abstinence rates were 9 % for the minimal intervention strategy for lung patients ( LMIS ) and 19 % for the SmokeStopTherapy ( SST ) . The baseline characteristics that showed a significant univariate relationship with 1-year continuous abstinence ( p<.20 ) were included in the logistic regression model . This procedure was performed for each intervention separately . Variables that did not remain independent predictors were removed . RESULTS For the SST separately , no independent significant predictor remained . For the LMIS , attitude towards smoking cessation ( OR : 11.8 ; 95 % CI : 1.7 - 81.5 ; p=.013 ) and cotinine level ( OR : 2.1 ; 95 % CI : 1.08 - 3.93 ; p=.028 ) remained significant predictors . Within the LMIS , 31 % of the variance in continuous abstinence was explained by these variables ( p=.003 ) . CONCLUSION This study suggests that a moderately intensive intervention ( LMIS ) is primarily suitable for COPD patients with a positive attitude regarding smoking cessation . The more intensive SST can be an alternative for patients without such baseline characteristic . PRACTICE IMPLICATION S This stepped-care approach in smoking cessation counseling may be useful in clinical practice and will enable health care providers to match interventions to individual needs and increase efficiency OBJECTIVE To examine patient response to a smoking cessation program that combined a nicotine replacement system ( patch ) with telephone support . DESIGN R and omized trial . SETTING A large Midwestern HMO . PARTICIPANTS . Five hundred and nine smokers who attended orientation sessions where an overview of the study and the use of the nicotine patch was presented . INTERVENTION All subjects received a prescription for a nicotine replacement patch ( Prostep , Lederle Laboratories , Wayne , NJ ) . Participants were r and omly assigned to one of three intervention groups . Group I participants ( n = 166 ) received no additional support . Group II participants ( n = 167 ) were registered with a 24-hour telephone hotline . Group III participants ( n = 167 ) were registered with the 24-hour telephone hotline and received four follow-up telephone calls from health educators . OUTCOME MEASURE The primary outcome measure was smoking cessation . Subject satisfaction with study components was also evaluated . RESULTS Overall , there was no significant difference by group in smoking cessation rates : 20 % of patients in all three groups were smoke-free after 12 months . Few patients ( 1 % ) used the telephone hotline . The telephone follow-up did not have an impact on cessation rates , and most patients ( 92 % ) reported that the orientation session was useful . CONCLUSIONS The study experience has helped the HMO evaluate various study components and has had an impact on currently used telephone intervention strategies and educational material Background : Smoking cessation of patients with cancer can improve treatment efficacy and survival . Objective : To determine whether a motivational interviewing intervention increased successful smoking cessation attempts of patients with cancer attending a South Australian public hospital , as compared with usual care . Methods : A r and omized controlled trial was used to study 137 patients with mixed cancer sites , including 74 intervention patients and 63 control patients . The motivational interviewing intervention was delivered over a 3-month period . The intervention included a visit with a smoking cessation counselor , provision of smoking cessation booklets , nicotine replacement therapy , family advice to quit , and an in-person or telephone follow-up conversation . Results : At the 6-month follow-up visit , an intention-to-treat analysis found no difference in biochemically confirmed 3-month prevalence quit rates between the intervention ( 5 % ) and control ( 6 % ) groups . A sensitivity analysis using more lenient criteria indicated quit rates of 29 % for the intervention group and 18 % for the control group ( p = .32 ) . The predictors of smoking cessation at 6 months for all the patients included a smoking-related cancer site , more cessation attempts in the year before enrollment in the study , and no radiation therapy . Conclusions : Future efforts to improve smoking cessation in this patient group might focus on the delivery of more direct methods for encouraging spouse cessation and support to the patient in quitting , and the use of bupropion ( Zyban ) as an adjunct to cessation for this heavy smoking patient group The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease ( COPD ) increases the rate of smoking cessation . In total , 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and r and omly allocated to : confrontational counselling by a nurse with nortriptyline for smoking cessation ( experimental group ) ; regular counselling by a nurse with nortriptyline ( control group 1 ) ; or “ care as usual ” for smoking cessation by the general practitioner ( control group 2 ) . Only the experimental group was confronted with their abnormal spirometry ( mean forced expiratory volume in one second ( FEV1 ) post-bronchodilator 80.5 % predicted , mean FEV1/forced vital capacity post-bronchodilator 62.5 % ) . There was no difference in cotinine-vali date d prolonged abstinence rate between the experimental group ( 11.2 % ) and control group 1 ( 11.6 % ) from week 5–52 ( odds ratio ( OR ) 0.96 , 95 % confidence interval ( CI ) 0.43–2.18 ) . The abstinence rate was approximately twice as high in the experimental group compared with control group 2 ( 5.9 % ) , but this difference was not statistically significant ( OR 2.02 , 95 % CI 0.63–6.46 ) . The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry . The high failure rates ( ≥88 % ) highlight the need for treating tobacco addiction as a chronic relapsing disorder The purpose of this study was to test two combination motivational plus pharmacological interventions for smoking cessation among HIV positive smokers . Participants were 40 adults receiving HIV care who smoked daily reporting interest in smoking reduction . Measures were administered at baseline , 1-month , and 3-month follow-ups . Participants were r and omly assigned to self-guided reading plus nicotine patch ( n = 18 ) or motivational interviewing plus nicotine patch ( n = 22 ) . Groups did not differ at 3 months on biochemically-verified abstinence . The sample reduced cigarettes per day by half a pack and the percent of smoking days by 41 % , and 22 % were abstinent at 3-month follow-up . Compliance with the nicotine patch was poor and declined over time , but patch use was unrelated to carbon monoxide level at 3-month follow-up . Smoking cessation interventions for people with HIV can be helpful and should include components that encourage some smoke-free days , increase self-efficacy , and attend to adherence to nicotine replacement treatment BACKGROUND Little is known about the effectiveness of bupropion SR for smoking cessation outside the context of clinical efficacy trials , where in-person screening and treatment occur at a higher level than provided in a typical health care system . This article describes the methods for recruitment , screening for exclusions , and result ing sample in a field trial of bupropion SR undertaken in a managed-care setting . METHODS A total of 2979 telephone interviews were conducted to screen and identify eligible volunteers using a detailed protocol that allowed for consultation with study physicians when necessary . The volunteers ' primary care physicians were given the option to override their eligibility , and pharmacy data bases were used to verify medication reporting . RESULTS A total of 1909 ( 64 % ) volunteers were considered eligible for the study . The most common reason for exclusion was use of contraindicated medications ( 32 % ) , followed by recent use of one of the behavioral cessation programs ( 14 % ) , brain injury that reduced seizure threshold ( 14 % ) , current depression ( 14 % ) , and high levels of alcohol use ( 13 % ) . CONCLUSIONS The methods used in this field trial show that it is possible to enroll subjects in an effectiveness trial that is successful from the st and point of the consumer , provider , and health care system AIMS To determine , in the context of a trial in which counseling did not improve smoking cessation outcomes , whether this was due to a failure of the conceptual theory identifying treatment targets or the action theory specifying interventions . DESIGN Data from a r and omized clinical trial of smoking cessation counseling and bupropion SR were su bmi tted to multi-level modeling to test whether counseling influenced real-time reports of cognitions , emotions and behaviors , and whether these targets predicted abstinence . SETTING Center for Tobacco Research and Intervention , Madison , WI . PARTICIPANTS A total of 403 adult , daily smokers without contraindications to bupropion SR use . Participants were assigned r and omly to receive individual counseling or no counseling and a 9-week course of bupropion SR or placebo pill . Cessation counseling was delivered in eight 10-minute sessions focused on bolstering social support , motivation , problem-solving and coping skills . MEASUREMENTS Pre- and post-quit ecological momentary assessment s of smoking behavior , smoking triggers , active prevention and coping strategies , motivation to quit , difficulty quitting and reactions to initial lapses . FINDINGS Counseling prompted avoidance of access to cigarettes , improved quitting self-efficacy , reduced perceived difficulty of quitting over time and protected against guilt and demoralization following lapses . Results also supported the importance of limiting cigarette access , receiving social support , strong motivation and confidence and easing withdrawal distress during cessation efforts . Quitting self-efficacy and perceived difficulty quitting may partially mediate counseling effects on abstinence . CONCLUSIONS Smoking cessation counseling may work by supporting confidence about quitting and reducing perceived difficulty quitting . Counseling did not affect other targets that protect against relapse OBJECTIVES Examine the effectiveness of an intervention to increase fruits and vegetables ( FV ) consumption among smokers . DESIGN Cluster-r and omized trial of 20 public housing developments ; 10 r and omly assigned to an FV intervention and 10 to a smoking cessation intervention . MAIN OUTCOME MEASURES Usual ( past 7 days ) and past 30 days change in daily FV intake at 8 weeks and 6 months postbaseline . RESULTS Greater increases were seen in the FV group . At Week 8 and Month 6 , the FV group had consumed 1.58 ( p = .001 ) and 0.78 ( p = .04 ) , respectively , more daily FV servings in the past 7 days than the cessation group . At the same time points , the FV group had consumed 3.61 ( p = .01 ) and 3.93 ( p = .01 ) , respectively , more FV servings in the past 30 days than the cessation group . Completing more motivational interviewing sessions ( p = .02 ) and trying more recipes ( p = .02 ) led to significantly greater increases at Month 6 among FV participants . CONCLUSIONS Motivational interviewing counseling and lifestyle modification through trying out healthy recipes may be effective in helping a high-risk population increase their FV intake Compared to the general population , smokers with schizophrenia ( SCZ ) have reduced success in quitting smoking with usual approaches . This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia ( TANS ) or Medication Management (MM)-for smokers who were motivated to quit . Individual counseling sessions were provided by mental health clinicians in mental health setting s , along with nicotine patch . The two treatments varied in intensity and frequency of sessions . Eighty-seven subjects were r and omized and attended at least one treatment session . Twenty-one percent ( n = 18 ) of participants had continuous abstinence at 12 weeks after the target quit date , which was not significantly different between conditions ( 15.6 % TANS vs. 26.2 % MM , chi(2 ) = 1.50 , p = .221 ) . Smokers in both groups significantly reduced smoking as measured by cigarettes per day and expired carbon monoxide . Findings support that mental health clinicians can be trained to effectively help smokers with SCZ maintain tobacco abstinence Objectives : This study evaluated the effectiveness of behavioral interventions ( brief counseling , nonspecific psychological support in groups — NSGS and cognitive behavioral group therapy — CBGT ) in combination with bupropion SR for smoking cessation in the field , through a smoking cessation clinic . Methods : Two-hundred- and -five smokers were enrolled in a 19-week course during 2007/ 2008 , and were r and omly assigned to : bupropion SR combined with brief counseling ( group A ) , bupropion SR combined with NSGS ( group B ) , bupropion SR combined with CBGT ( group C ) , or CBGT as the only approach ( group D ) . Results : Continuous abstinence rates at the end of therapy were 53.2 % for group A , 62.9 % for group B , 50.0 % for group C , and 22.2 % ( p < 0.05 ) for group D. Sustained abstinence rates in 12 months were 29.6 % , 28.1 % , 34.3 % and 19.4 % ( p > 0.05 ) , respectively . Conclusions : Bupropion SR is an effective aid for smoking cessation in clinical practice . NSGT increased the chances for success at the end of therapy when combined with bupropion SR , while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy . It is suggested that smoking cessation interventions in real-life healthcare setting s should be implemented through comprehensive programs using pharmacotherapy where applicable , combined with NSGT , and integrated by specialized healthcare professionals This study examines the efficacy of a smoking cessation intervention on abstinence rates and motivation to quit smoking . Participants were adult smokers ( N = 543 ) who presented to the emergency department with chest pain and who were admitted to an observation unit for 24-hour observation to rule out myocardial infa rct ion . Participants were r and omly assigned to either usual care or a tailored intervention employing motivational interviewing and telephone follow-up . All individuals choosing to quit were offered nicotine patch therapy . Follow-up assessment s were conducted at 1 , 3 and 6 months . Abstinence ( 7-day point prevalence ) rates were significantly greater among participants receiving the tailored intervention compared with those given usual care ( OR = 1.62 , 95 % CI [ 1.05 - 2.50 ] ) . The largest difference occurred at 1 month : 16.8 % of usual care and 27.3 % of the tailored intervention group were abstinent , with differences decreasing over time . One-third of participants who were quit at month 6 were late quitters whose initial abstinence began after the 1-month follow up . In addition to treatment assignment , psychosocial variables including motivation to quit , confidence , reduced temptation to smoke in response to negative affect , and the perception that their chest pain was related to their smoking , were significant predictors of cessation . Tailored interventions are effective in promoting initial quit attempts for emergency chest pain patients admitted to an observation unit . Additional intervention may be needed to assist late quitters and to prevent relapse OBJECTIVES An analysis of gender differences in smoking cessation was conducted among 3923 participants in the Special Intervention group of the Lung Health Study . This report focuses on gender differences in sustained quit rates at 12 and 36 months . METHODS Special Intervention participants were offered a 12-session , 12-week smoking cessation program using nicotine gum and were followed for 3 years . Self-reported smoking status was vali date d with carbon monoxide and salivary cotinine . RESULTS Men had higher sustained quit rates at 12 and 36 months ; gender differences were found in baseline variables that also predicted sustained abstinence ; and controlling for selected baseline variables reduced the association between gender and sustained abstinence . When other variables were controlled , gender predicted sustained abstinence at 36 months ( odds ratio [ OR ] = 1.24 , 95 % confidence interval [ CI ] = 1.04 , 1.48 ) but not 12 months ( OR = 1.08 , 95 % CI = 0.92 , 1.27 ) , reflecting more late relapse among women . CONCLUSIONS Demographics and smoking history were more important than gender per se in sustained smoking cessation in the Lung Health Study . Programs tailoring smoking cessation by gender need to include coping skills for problems associated with less education and social support and for improving persistence with quit attempts Background . The aim was to study the effect of a multimodal smoking cessation intervention regimen on a number of pregnant smokers Two hundred smokers who were judged by their general practitioner to be motivated to stop smoking were allocated to one of two groups . All were offered an initial appointment at which they were advised to stop smoking and offered nicotine gum . One group then received no further appointments . The other was offered four further appointments over three months . Both groups were followed up at six and 12 months . At one year follow up 15.5 % overall had stopped smoking , 14 % in the low and 17 % in the high contact group . This is better than most results so far reported for nicotine chewing gum in general practice , suggesting that general practitioners can use it to good effect . We compare this result with others achieved in general practice BACKGROUND The Agency for Healthcare Research and Quality Smoking Cessation Practice Guideline recommends systematic assessment of smoking status and counseling of smokers at every visit , but the actual effectiveness of the guideline in primary care practice is unknown . METHODS We conducted a nonr and omized , controlled before-after trial of a guideline -derived intervention that includes routine identification and brief counseling of smokers by nurses and medical assistants , coupled with free nicotine replacement therapy ( NRT ) and telephone counseling of those smokers who are willing to make a quit attempt , and feedback on performance of guideline -recommended activities . The intervention was pilot tested at 1 family practice ( FP ) clinic over a 2-month period ; patterns of usual care were observed concurrently at four control FP clinics . We obtained exit interviews of 651 consecutive adult smokers who presented for routine , nonemergency care . Abstinence ( 7-day point prevalence ) was determined by telephone interview during 6-month follow-up . RESULTS Concordance with guidelines was significantly greater for all recommended actions at the test site during the intervention versus baseline ( P < or = 0.05 ) . Significantly more intervention versus baseline patients at the test site reported abstinence at 2-month follow-up ( 21 vs. 4 % , P = 0.0004 ) , and more patients tended to be abstinent at 6-month follow-up ( 21 vs. 11 % , P = 0.08 ) . No significant differences in 2- or 6-month quit rates between intervention and baseline patients were observed at the control sites . CONCLUSIONS Implementation of a guideline -driven smoking cessation intervention that focuses primarily on smokers who are interested in making a quit attempt is associated with increased abstinence in primary care practice The Lung Health Study is a multicenter r and omized clinical trial . Participants are smokers aged 35 - 60 with spirometric evidence of moderate lung function impairment . The objective of the trial is to determine whether a program of smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in pulmonary function over a 5-year follow-up period . This paper describes the background , design , sample size ( approximately 6000 participants ) , and power estimates for the trial , as well as the treatment program and the rationale for the choice of inhaled bronchodilator . Plans for analysis of changes in pulmonary function parameters and for analysis of participants ' survival and smoking-related morbidity are also discussed INTRODUCTION Despite decades of tobacco use decline among the general population in the United States , tobacco use among low-income population s continues to be a major public health concern . Smoking rates are higher among individuals with less than a high school education , those with no health insurance , and among individuals living below the federal poverty level . Despite these disparities , smoking cessation treatments for low-income population s have not been extensively tested . In the current study , the efficacy of 2 adjunctive smoking cessation interventions was evaluated among low-income smokers who were seen in a primary care setting . METHODS A total of 846 participants were r and omly assigned either to motivational enhancement treatment plus brief physician advice and 8 weeks of nicotine replacement therapy ( NRT ) or to st and ard care , which consisted of brief physician advice and 8 weeks of NRT . Tobacco smoking abstinence was at 1 , 2 , 6 , and 12 months following baseline . RESULTS The use of the nicotine patch , telephone counseling , and positive decisional balance were predictive of increased abstinence rates , and elevated stress levels and temptation to smoke in both social/habit and negative affect situations decreased abstinence rates across time . Analyses showed intervention effects on smoking temptations , length of patch use , and number of telephone contacts . Direct intervention effects on abstinence rates were not significant , after adjusting for model predictors and selection bias due to perir and omization attrition . CONCLUSIONS Integrating therapeutic approaches that promote use of and adherence to medications for quitting smoking and that target stress management and reducing negative affect may enhance smoking cessation among low-income smokers INTRODUCTION Patient adherence to smoking cessation medications can impact their effectiveness . It is important to underst and the extent to which prescribed medications are actually taken by smokers , how this influences smoking cessation outcomes , and what factors may influence adherence . METHODS Smokers recruited from a large health plan were r and omized to receive different modes of cessation counseling in combination with varenicline ( Swan , G. E. , McClure , J. B. , Jack , L. M. , Zbikowski , S. M. , Javitz , H. S. , Catz , S. L. , et al. 2010.Behavioral counseling and varenicline treatment for smoking cessation . American Journal of Preventive Medicine , 38 , 482 - 490 ) . One thous and one hundred and sixty-one participants were mailed a 28-day varenicline supply when they set a quit date and were able to request up to two refills from the health plan pharmacy at no cost . Pharmacy fill records were obtained and telephone surveys completed at baseline , 21 days , 12 weeks , and 6 months post target quit date . RESULTS Good adherence to varenicline ( ≥80 % of days taken ) was associated with a twofold increase in 6-month quit rates compared with poor adherence ( 52 % vs. 25 % ) . Smokers were more likely than nonsmokers to stop varenicline early . Purpose ful nonadherence was associated with smoking at 12 weeks and was predicted in multivariate analyses by age , gender , adherence self-efficacy , and initial medication side effect severity . CONCLUSIONS Innovative methods for increasing adherence to smoking cessation medications are needed , particularly early in the quit process . Simple metrics of adherence such as number of days cessation medication is taken can and should be routinely incorporated in effectiveness trials and reported to advance future attempts to underst and and reduce nonadherence The authors evaluated whether completing a multi-item assessment of smoking craving ( the Question naire of Smoking Urges [ QSU ] ) promoted increases in smoking craving . A sample of 39 regular smokers was r and omly assigned to 1 of 3 manipulations ( each of 3 min duration ): ( a ) complete the QSU-Brief ( 10 items ) , ( b ) complete a noncraving question naire that was structurally identical to the QSU-Brief ( scale-based control ) , and ( c ) a time-based control . Participants responded to an oral question assessing their degree of craving immediately before and after the manipulations . Results indicated that the QSU did not promote increases in craving compared to the 2 control conditions . Despite continuing debate over the most appropriate self-report measure of craving , investigators who use the QSU-Brief can be reasonably sure that the scores that result are not biased due to reactivity effects 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 To determine predictors of smoking cessation duration in a r and omized clinical trial , we assigned participants to nicotine patch ( 8 - 12 weeks ) plus either ( a ) a baseline tailored brief motivational intervention , a quit date behavioral skills counseling session , and a relapse prevention follow-up session , or ( b ) brief advice using the National Cancer Institute 's 4A 's model . A total of 383 smokers from five methadone maintenance treatment centers in Rhode Isl and were enrolled , of whom 312 ( 82 % ) completed 6-month follow-up assessment s. The primary outcome was longest period of self-reported abstinence during follow-up . Participants were on average 40.5 years of age ; 51.9 % were male , and 77.6 % were White . In multivariate analysis controlling for demographics , nicotine dependence , depressive symptoms , and smoking-related symptoms , we found longer periods of abstinence in persons reporting at least one 24-hr quit attempt in the year prior to baseline ( OR = 1.97 , p = .003 ) , in those anticipating success in cessation ( OR = 1.33 , p = .024 ) , and in those with a greater percentage of nicotine patch use days ( OR = 2.78 , p<.001 ) . Past quit attempts , self-efficacy , and constant nicotine replacement were associated with duration of abstinence among methadone-maintained smokers . Attention to these domains in future intervention studies may improve treatment success PURPOSE To determine whether an intensive cognitive-behavioral intervention begun during hospitalization when combined with transdermal nicotine replacement therapy is more effective than a minimal counseling intervention combined with transdermal nicotine replacement therapy in helping in patients to quit smoking . METHODS A total of 223 patients who smoked were enrolled in a hospital-based r and omized smoking cessation trial at the San Francisco Veterans Affairs Medical Center . One hundred and seven participants ( 48 % ) received intensive counseling and outpatient telephone follow-up ; 116 participants ( 52 % ) received minimal counseling . All study participants received 2 months of transdermal nicotine replacement therapy . We determined 6-month quit rates by self-report and measured saliva cotinine levels or obtained proxy reports to confirm self-reported smoking cessation at 12 months . Analyses adjusted for baseline differences in the distribution of coronary disease . RESULTS At 6 months , 35 % ( 36/103 ) of the intensive intervention group reported quitting , compared with 21 % ( 23/109 ) of the comparison group ( relative risk [ RR ] = 1.7 ; 95 % confidence interval [ CI ] : 1.1 to 2.7 ) . At 12 months , the self-reported quit rate was 33 % ( 33/99 ) in the intensive intervention group versus 20 % ( 21/103 ) in the comparison group ( RR = 1.7 ; 95 % CI : 1.1 to 2.7 ) . Based on biochemical or proxy confirmation , 29 % ( 30/102 ) in the intensive intervention group versus 20 % ( 21/107 ) in the comparison group quit smoking at 12 months ( RR = 1.6 ; 95 % CI : 0.96 to 2.5 ) . CONCLUSION Hospital-initiated smoking cessation interventions that include transdermal nicotine replacement therapy can improve long-term quit rates IMPORTANCE Health care systems need effective models to manage chronic diseases like tobacco dependence across transitions in care . Hospitalizations provide opportunities for smokers to quit , but research suggests that hospital-delivered interventions are effective only if treatment continues after discharge . OBJECTIVE To determine whether an intervention to sustain tobacco treatment after hospital discharge increases smoking cessation rates compared with st and ard care . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial compared sustained care ( a postdischarge tobacco cessation intervention ) with st and ard care among 397 hospitalized daily smokers ( mean age , 53 years ; 48 % were males ; 81 % were non-Hispanic whites ) who wanted to quit smoking after discharge and received a tobacco dependence intervention in the hospital ; 92 % of eligible patients and 44 % of screened patients enrolled . The study was conducted from August 2010 through November 2012 at Massachusetts General Hospital . INTERVENTIONS Sustained care participants received automated interactive voice response telephone calls and their choice of free smoking cessation medication ( any type approved by the US Food and Drug Administration ) for up to 90 days . The automated telephone calls promoted cessation , provided medication management , and triaged smokers for additional counseling . St and ard care participants received recommendations for postdischarge pharmacotherapy and counseling . MAIN OUTCOMES AND MEASURES The primary outcome was biochemically confirmed past 7-day tobacco abstinence at 6-month follow-up after discharge from the hospital ; secondary outcomes included self-reported tobacco abstinence . RESULTS Smokers r and omly assigned to sustained care ( n = 198 ) used more counseling and more pharmacotherapy at each follow-up assessment than those assigned to st and ard care ( n = 199 ) . Biochemically vali date d 7-day tobacco abstinence at 6 months was higher with sustained care ( 26 % ) than with st and ard care ( 15 % ) ( relative risk [ RR ] , 1.71 [ 95 % CI , 1.14 - 2.56 ] , P = .009 ; number needed to treat , 9.4 [ 95 % CI , 5.4 - 35.5 ] ) . Using multiple imputation for missing outcomes , the RR for 7-day tobacco abstinence was 1.55 ( 95 % CI , 1.03 - 2.21 ; P = .04 ) . Sustained care also result ed in higher self-reported continuous abstinence rates for 6 months after discharge ( 27 % vs 16 % for st and ard care ; RR , 1.70 [ 95 % CI , 1.15 - 2.51 ] ; P = .007 ) . CONCLUSIONS AND RELEVANCE Among hospitalized adult smokers who wanted to quit smoking , a postdischarge intervention providing automated telephone calls and free medication result ed in higher rates of smoking cessation at 6 months compared with a st and ard recommendation to use counseling and medication after discharge . These findings , if replicated , suggest an approach to help achieve sustained smoking cessation after a hospital stay . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01177176 INTRODUCTION An inability to tolerate distress is a significant predictor of early smoking lapse following a cessation attempt . We conducted a preliminary r and omized controlled trial to compare a distress tolerance ( DT ) treatment that incorporated elements of exposure-based therapies and Acceptance and Commitment Therapy to st and ard smoking cessation treatment ( ST ) . METHODS Smokers with a history of early lapse in prior quit attempts received either DT ( N = 27 ; 9 2-hr group and 6 50-min individual sessions ) or ST ( N = 22 ; 6 90-min group and 1 20-min individual session ) , plus 8 weeks of transdermal nicotine patch . RESULTS At the end of behavioral treatment , odds of abstinence among participants receiving DT were 6.46 times greater than among participants receiving ST ( 66.7 % vs. 31.8 % ) , equivalent to a medium- to large-effect size . Odds of abstinence for DT were still 1.73 times greater at 8 weeks , corresponding to a small- to medium-effect size , although neither this difference nor those at 13 and 26 weeks were statistically significant . Furthermore , of those who lapsed to smoking during the first week postquit , DT participants had more than 4 times greater odds of abstinence than ST participants at the end of treatment . Relative to ST , DT participants also reported a larger decrease in experiential avoidance , a hypothesized DT treatment mediator , prior to quit day . The trajectory of negative mood and withdrawal symptoms in DT differed from ST and was largely consistent with hypotheses . CONCLUSIONS Reasons for the decrease in abstinence in DT after treatment discontinuation and suggestions for future research are discussed We tested an intervention to help smokers abstain ( fast ) from smoking before surgery , maintain abstinence postoperatively , and achieve long-term cessation . A r and omized experiment included 237 patients admitted for presurgical assessment who smoked . The intervention included counseling and nicotine replacement therapy . Treatment group participants ( 73.0 % ) were more likely to fast than were controls ( 53.0 % ) : chi(2)(1 , N = 228 ) = 8.89 , p = .003 , and more likely to be abstinent 6 months after surgery ( 31.2 % vs. 20.2 % ) . There was no significant difference in the abstinence rates at 12 months after surgery , chi(2)(1 , N = 169 ) < .001 , p = 1.00 . Encouraging patients to fast from smoking before surgery and postoperative support are efficacious ways to reduce preoperative and immediate post-operative tobacco use BACKGROUND : Cigarette smoking by surgical patients is associated with increased complications , particularly perioperative respiratory problems and poor wound healing . In this study , we sought to determine whether a pragmatic perioperative smoking cessation intervention design ed for a busy preadmission clinic would be successful in reducing smoking rates and intraoperative and immediate postoperative complications . METHODS : This r and omized controlled trial was conducted at a university-affiliated hospital in London , Ontario , Canada . Patients seen in the preadmission clinic at least 3 weeks preoperatively were r and omized to either the control group ( 84 patients ) or the intervention group ( 84 patients ) . The control group received no specific smoking cessation intervention . The intervention group received ( 1 ) brief counseling by the preadmission nurse , ( 2 ) brochures on smoking cessation , ( 3 ) referral to the Canadian Cancer Society ’s Smokers ’ Helpline , and ( 4 ) a free 6-week supply of transdermal nicotine replacement therapy . All outcome assessors and caregivers on the operative day were blinded to group assignment . The primary outcome was the rate of smoking cessation as confirmed by exhaled carbon monoxide breath test . Secondary outcomes included perioperative complications and smoking status at 30 days postoperatively . RESULTS : Between October 2010 and April 2012 , 168 patients were recruited into the study . Smoking cessation occurred in 12 patients ( 14.3 % ) in the intervention group as compared with 3 patients ( 3.6 % ) in the control group ( relative risk 4.0 ; 95 % confidence interval [ CI ] , 1.2–13.7 ; P = 0.03 ) . The overall rate of combined intraoperative and immediate postoperative complications was not significantly different between intervention and control groups ( 13.1 % and 16.7 % , respectively ; relative risk 0.79 ; 95 % CI , 0.38–1.63 ; P = 0.67 ) . At follow-up 30 days postoperatively , smoking cessation was reported in 22 patients ( 28.6 % ) in the intervention group compared with 8 patients ( 11 % ) in controls ( relative risk 2.6 ; 95 % CI , 1.2–5.5 ; P = 0.008 ) . CONCLUSIONS : One of the objections to widespread use of smoking cessation interventions in the preadmission clinic is that it is too labor-intensive . The results of this study show that a smoking cessation intervention , design ed to minimize additional use of physician or nursing time , results in decreased smoking rates on the day of surgery and promotes abstinence 30 days postoperatively Health care increasingly incorporates telephone counseling , but the interactions supporting its delivery are not well understood . The authors ’ clinical trial of a tailored , nurse-administered smoking cessation intervention for surgical patients included a telephone counseling component and provided an opportunity to describe the interaction dynamics of proactive telephone counseling over the course of 4 months . Tape-recorded telephone counseling calls for 56 consecutively enrolled individuals r and omized to the intervention group result ed in a data set of 368 calls , which were transcribed and analyzed using constant comparative methods . The findings revealed varying interaction dynamics depending on the nurse ’s level of engagement with participants and participants ’ motivation to stop smoking . The authors identified four interaction dynamics : affirming/working , chasing/skirting , controlling/withdrawing , and avoiding commitment . Shifts in interaction dynamics were common and influenced the provision of support both positively and negatively . The findings challenge many assumptions underlying telephone counseling and suggest strategies to improve its delivery OBJECTIVE To assess the feasibility and potential effectiveness of a modified version of the Ottawa Model for Smoking Cessation in an outpatient respirology clinic . METHODS Adult tobacco smokers attending the respirology clinic and willing to choose a quit date within one month of enrollment were r and omly assigned to receive st and ard care or the intervention . St and ard care participants received smoking cessation advice , a brochure and a prescription for smoking cessation medication if requested . Intervention participants received a $ 110 voucher to purchase smoking cessation pharmacotherapy and were registered to an automated calling system . Answers to automated calls determined which participants required nurse telephone counselling . Feasibility indicators included recruitment and retention rates , and intervention adherence . The effectiveness indicator was self-reported smoking status at 26 to 52 weeks . RESULTS Forty-nine ( 54.4 % ) of 90 eligible smokers were r and omly assigned to the intervention ( n=23 ) or control ( n=26 ) group . Self-reported smoking status at 26 to 52 weeks was available for 32 ( 65.3 % ) participants . The quit rate for intervention participants was 18.2 % compared with 7.7 % for controls ( OR2.36 [ 95 % CI 0.39 to 14.15 ] ) . CONCLUSION It would be feasible to evaluate this intervention in a larger trial . Alternatives to face-to-face follow-up at the clinic are recommended PURPOSE To conduct an exploratory study of two interventions to help smokers abstain over a period of 3 months . The specific aims were to describe the outcomes , test feasibility of the study design , and evaluate effect size . DESIGN AND METHODS A r and omized experimental design was used in a sample of 42 patients who received multicomponent treatment intervention ( MTI ) or st and ard care ( SC ) in a midwestern city in the United States . Variables were behavioral ( quit rate , self-efficacy , motivation ) , psychosocial ( depression , partner interaction ) , and symptom management ( use of nicotine replacement therapy [ NRT ] ) . Data analysis included descriptive statistics and repeated measures ANOVA . RESULTS The typical participant was Caucasian , middle aged , nicotine dependent , married or partnered , and employed , and had a high school education . Participants in the MTI group were more likely to use NRT and to have higher self-reported quit rates at follow-up . Statistically significant differences were found between groups over time for self-efficacy and positive to negative behavior ratio . Barriers to quitting were relapse , stress , weight gain , lack of support , and depression that were more frequent in the SC group . For effect size ( 0.25 ) , probability level ( .05 ) , and power ( .80 ) , a sample size of 140 patients was calculated . CONCLUSIONS The MTI group had higher quit rates , more NRT , higher self-efficacy , and more positive behavioral interactions . Limitations of the study included self-report of tobacco use , small sample , and attrition . The investigators suggest a future study with a larger sample to test whether multicomponent interventions with telephone calls after discharge are more effective than is st and ard care in helping patients to quit and continue to abstain from smoking ABSTRACT Little is known about the relative , additive , and interactive effects of different population -based treatments for smoking cessation . The goal of this study was to evaluate the main and interactive effects of five different smoking interventions . Using the multiphase optimization strategy ( MOST ) , 1,034 smokers who entered a Web site for smokers ( smokefree.gov ) were r and omly assigned to the “ on ” and “ off ” conditions of five smoking cessation interventions : the National Cancer Institute ’s ( NCI ) Web site ( www.smokefree.gov vs a “ lite ” Web site ) , telephone quitline counseling ( vs none ) , a smoking cessation brochure ( vs a lite brochure ) , motivational e-mail messages ( vs none ) , and mini-lozenge nicotine replacement therapy ( NRT vs none ) . Analyses showed that the NCI Web site and NRT both increased abstinence ; however , the former increased abstinence significantly only when it was not used with the e-mail messaging intervention ( messaging decreased Web site use ) . The other interventions showed little evidence of effectiveness . There was evidence that mailed nicotine mini-lozenges and the NCI Web site ( www.smokefree.gov ) provide benefit as population -based smoking interventions Introduction : Although most smokers diagnosed with lung cancer report that they want to quit smoking , many do not succeed . Smokers who quit when lung cancer is diagnosed have improved treatment efficacy , quality of life , and survival . Effective smoking cessation interventions targeted to thoracic oncology patients are needed . Methods : This pilot study examined the feasibility and potential efficacy of a 12-week program that combined smoking cessation counseling with varenicline . Seven-day point prevalence tobacco abstinence rates at the end of treatment were compared with a usual care control group . From January 2008 to August 2009 , patients with a diagnosed or suspected thoracic malignancy were recruited at their initial visit to a thoracic surgeon or thoracic oncologist at Massachusetts General Hospital . Results : Of 1130 patients screened , 187 ( 17 % ) were current smokers , and an additional 66 ( 6 % ) reported quitting within the past 6 months . One hundred sixteen ( 67 % ) of smokers were eligible , and 49 ( 42 % ) of eligible smokers enrolled ( control group n = 17 , intervention group n = 32 ) . Intervention participants completed a median of nine counseling sessions ; 50 % of intervention participants completed the full varenicline course . At 12-week follow-up , biochemically vali date d 7-day point prevalence tobacco abstinence rates were 34.4 % in the intervention group versus 14.3 % in the control group ( odds ratio = 3.14 , 95 % confidence interval = 0.59–16.62 , p = 0.18 ) . Conclusion : Our findings support the feasibility and acceptability of this program . At the end of treatment , quit rates were higher in the control group . Further testing is indicated to establish the efficacy of this treatment package in a r and omized clinical trial OBJECTIVE The aim was to examine to what extent lifestyle , education , social support , and comorbidity predict the ability of perioperative smoking cessation , and are associated with the development of important postoperative complications . DESIGN The design was a r and omized clinical trial . SETTING University hospitals in Copenhagen , Denmark , were the setting s. PARTICIPANTS AND METHODS One hundred twenty patients scheduled for primary elective hip or knee arthroplasty were r and omized to either smoking intervention or st and ard care . Tobacco and alcohol consumption , exercise and eating habits , level of education , matrimonial status , and the presence of social support were registered . The data gathered concerned smoking cessation/reduction and severe postoperative morbidity . RESULTS Men and patients with a good social network were more likely to successfully quit smoking . Smoking intervention successfully reduced the incidence of postoperative complications , as did weekly exercise exceeding 4 h , and having a high education level . CONCLUSIONS This study emphasizes that smoking intervention programs in health care setting s are highly effective in reducing postoperative risks in hip and knee arthroplasty INTRODUCTION PLHIV have higher rates of smoking and lower motivation to quit smoking ; thus to impact smoking rates , cessation interventions need to be acceptable to a wider range of PLHIV smokers as well as feasible to implement in a busy clinical setting . The purpose of this study was to evaluate the acceptability , feasibility , and effects of a Screening , Brief Intervention , and Referral for Treatment ( SBIRT ) model in an HIV/AIDS clinic among a sample of PLHIV . METHODS PLHIV smokers ( N=40 ) were r and omized at baseline , irrespective of their self-reported discrete smoking cessation motivation status , to receive either 8-weeks of combination nicotine replacement therapy ( NRT ) in conjunction with brief counseling ( SBIRT framework ) ( n=23 ) or usual care ( n=17 ) . Smoking outcome measures included cigarettes smoked per day , nicotine dependence , smoking urge , and smoking withdrawal symptoms . RESULTS The SBIRT intervention appeared to be acceptable and feasible , and produced medium to large reductions in cigarettes smoked per day , physical nicotine dependence , smoking urge , and smoking withdrawal symptoms , even for smokers not ready to quit within 6months . CONCLUSIONS Findings provide preliminary support for the integration of an SBIRT model in an HIV/AIDS clinic setting to screen and provide active treatment to all smokers , regardless of readiness to quit smoking . Given the high prevalence and incredible health burden of continued smoking in this population , identifying brief and effective interventions that are easily translated into clinical practice represents an enormous challenge that if met , will yield significant improvements to overall patient outcomes Smokers ( N = 99 ) were r and omly assigned to one of three conditions : nicotine gum ( NG ) , nicotine gum plus psychological treatment ( NG-PT ) , and nicotine gum plus psychological treatment and partner support ( NG-PT-PS ) . Data were collected at Weeks 0 , 4 , 12 , 26 , and 52 from study start . Contrary to expectations , NG-PT-PS and NG-PT failed to increase abstinence rates . Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions , although not significantly at Weeks 26 and 52 . Treatments without partner participation ( NG-PT and NG ) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks . The role of social support in smoking treatment is discussed Analyses were made separately for men and women of the predictors of end-of-treatment ( 4 months ) smoking cessation and subsequent relapse at 12 and 24 months among 3,923 participants enrolled in the Lung Health Study 's 12-week cognitive-behavioral group smoking cessation program . Nicotine gum ( 2 mg ) was available to all participants . Men were more likely than women to quit smoking initially , but relapse rates were similar for both genders . Baseline variables associated with initial quitting for both genders included greater education , lower nicotine dependence , and fewer respiratory symptoms . The best predictor of relapse between 4 and 12 months was smoking at least 1 cigarette between quit day and 4 months . Nicotine gum use at 12 months predicted relapse by 24 months for both genders . Greater social and environmental support for quitting smoking were the only factors that predicted both initial quitting and relapse for both genders . Clinical implication s are discussed The patch adherence behavior of 101 smokers receiving 8 weeks of the nicodermal patch was examined while undergoing one of three levels of adjunctive psychosocial treatment . Additionally , regression analyses were undertaken to : ( 1 ) identify subject variables predictive of patch adherence and ( 2 ) to determine the predictive validity of patch treatment dropout , smoking and patch adherence during patch treatment to smoking 9 and 26 weeks post-treatment entry . Fifty-five percent of the patients wore the patch as prescribed for at least 50 of 56 treatment days . A multiple regression model including the Fagerström severity of dependence score , psychosocial treatment group , and the URICA commitment score predicted 18 % of the variance in days of patch use . All treatment dropouts were found to be smoking at followup . Although both smoking and low patch compliance during treatment were significant predictors subjects of week 9 and 26 smoking for the remaining subjects , at the individual variable level of analysis , only smoking during treatment predicted week 9 and 26 outcomes in a two-variable predictor model INTRODUCTION The purpose of this study was to investigate the efficacy of an intensive tobacco cessation intervention for alcohol-dependent smokers in early recovery . METHODS A total of 162 alcohol-dependent smokers were r and omized to either intensive intervention for smoking cessation or usual care . The intensive intervention consisted of 16 sessions of individual cognitive behavior therapy ( CBT ) and combination nicotine replacement therapy that lasted 26 weeks . Usual care involved referral to a free-st and ing smoking cessation program that provided smoking cessation counseling of varying duration and guideline -concordant medications . The primary cessation outcome was verified 7-day point prevalence abstinence ( PPA ) at 12 , 26 , 38 , and 52 weeks . RESULTS At 12 and 26 weeks , the verified 7-day point-prevalence quit rate was significantly higher for the intensive intervention group than for the usual care group ( both p=0.03 ) . However , the quit rates for the two treatment groups were not significantly different at 38 or 52 weeks . Verified 30-day alcohol abstinence rates were not significantly different for the two treatment groups at any of the follow-up assessment s. CONCLUSIONS The intensive smoking cessation intervention yielded a higher short-term smoking quit rate without jeopardizing sobriety . A chronic care model might facilitate maintenance of smoking cessation during the first year of alcohol treatment and perhaps for longer periods of time . It is hoped that studies such as this will inform the development of more effective interventions for concurrent alcohol and tobacco use disorders OBJECTIVES We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation , reduction in tobacco use , number of quit attempts , and change in readiness to quit . METHODS We r and omized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states ( Mississippi , New York , and Oregon ) to the intervention ( brief advice and assistance , including nicotine replacement therapy ) or usual care group . RESULTS We enrolled 2549 smokers . Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up , for both point prevalence ( F(1,12 ) = 6.84 ; P < .05 ) and prolonged abstinence ( F(1,12 ) = 14.62 ; P < .01 ) than did those in the usual care group . CONCLUSIONS The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers . Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans We tested whether a 3-month beneficial effect of telephone counseling as an adjunct to the use of medications for smoking cessation was maintained through 12 months . Health plan members filling a prescription for cessation medications were r and omized either to a no-contact control group or to proactive recruitment into telephone counseling . An increased point-prevalence quit rate at 3 months ( 33.1 % vs. 27.4 % , p<.05 ) among smokers r and omized to proactive recruitment for telephone counseling was not maintained . Although at 12 months smokers in the proactive recruitment arm were more likely to report a 24-hr quit attempt , compared with control group smokers ( 86.7 % vs. 80.8 % , p = .027 ) , we found no differences between the groups in repeated ( 3-month and 12-month ) 7-day point-prevalence quit rates . In an analysis of predictors of quitting , age , marital status , making a lifestyle change , and the presence of household smokers were associated with repeated 3-month and 12-month point-prevalence abstinence . Offering telephone counseling to insured smokers who have filled prescriptions for cessation medications did not increase long-term quit rates . Although other variations of this approach might be tested , we suspect that it might be more useful to test innovative ways to influence the factors we identified as being most strongly predictive of lack of successful quitting INTRODUCTION Bupropion and cognitive-behavioral treatment ( CBT ) for depression have been used as components of treatments design ed to alleviate affective disturbance during smoking cessation . Studies of treatment-related changes in precessation affect or urges to smoke are needed to evaluate the proposed mechanisms of these treatments . METHODS The present report examines affective trajectories and urges to smoke prior to , on quit day , and after quitting in a sample of 524 smokers r and omized to receive bupropion versus placebo and CBT versus st and ard smoking cessation CBT . RESULTS Bupropion and /or CBT did not affect the observed decreases in positive affect and increases in negative affect prior to cessation . However , on quit day , observed levels of negative affect and urges to smoke were diminished significantly among individuals receiving bupropion . Decreases in positive affect prior to quitting , lower levels of positive affect , and increased levels of negative affect and urges to smoke on quit day were each related to higher risk of smoking lapse . Depression proneness was an independent predictor of lower positive affect and higher negative affect but did not moderate the effects of bupropion on outcomes . In mediational analyses , the effect of bupropion was accounted for in part by lower negative affect and urges to smoke on quit day . DISCUSSION Results support the efficacy of bupropion in reducing relapse risk associated with urges to smoke and negative affect and suggest the need to better underst and the role of low positive affect as a risk factor for early lapse This study evaluated a treatment combining bupropion with a novel acceptance and relationship focused behavioral intervention based on the acceptance and relationship context ( ARC ) model . Three hundred and three smokers from a community sample were r and omly assigned to bupropion , a widely used smoking cessation medication , or bupropion plus functional analytic psychotherapy ( FAP ) and acceptance and commitment therapy ( ACT ) . Objective measures of smoking outcomes and self-report measures of acceptance and relationship processes were taken at pretreatment , posttreatment , 6-month , and 1-year follow-up . The combined treatment was significantly better than bupropion alone at 1-year follow-up with 7-day point prevalence quit rates of 31.6 % in the combined condition versus 17.5 % in the medication-alone condition . Acceptance and the therapeutic relationship at posttreatment statistically mediated 12-month outcomes . Bupropion outcomes were enhanced with an acceptance and relationship focused behavioral treatment INTRODUCTION Clinical trials are needed to inform evidence -based smoking cessation approaches in rural and Appalachian women , but trial enrollment in these groups is sparse . Little is known about factors associated with enrollment of Appalachian women in tobacco dependence treatment r and omized clinical trials ( RCT ) . We report a comparison of Appalachian women enrolling in a tobacco dependence treatment RCT to those declining and identify correlates to enrollment . METHODS Smokers identified during a cervical health-related survey among Ohio Appalachian women were invited to enroll in a tobacco dependence treatment RCT incorporating behavioral counseling and nicotine replacement . Women who agreed to enroll were compared to women who declined in terms of sociodemographic , health- and smoking-related measures . RESULTS The mean age of women sample d was 35.1 years . Women reported daily consumption of 1 - 10 ( 39 % ) , 11 - 20 ( 46 % ) , or > 20 ( 16 % ) cigarettes . In a multivariable logistic regression model adjusting for age and nicotine dependence , pros of smoking most outweighing cons ( odds ratio [ OR ] = 0.11 , 95 % confidence intervals [ CI ] = 0.03 , 0.39 ) , ≥3 prior quit attempts versus 1 attempt ( OR = 0.18 , 95 % CI = 0.06 , 0.59 ) , and not having health insurance ( OR = 0.29 , 95 % CI = 0.12 , 0.77 ) were associated with decreased odds of RCT enrollment . CONCLUSIONS Rural Appalachian women who enrolled in a tobacco dependence treatment RCT differed significantly in motivational and cognitive attitudes toward smoking , insurance status , and number of prior quit attempts , as compared to those who did not enroll . Techniques that foster motivation to quit smoking as a means of boosting RCT enrollment are discussed INTRODUCTION In an ethnically-diverse , uninsured psychiatric sample with co-occurring drug/alcohol addiction , we evaluated the feasibility and reproducibility of a tobacco treatment intervention . The intervention previously demonstrated efficacy in insured psychiatric and nonpsychiatric sample s with 20.0%-25.0 % abstinence at 18 months . METHODS Daily smokers , recruited in 2009 - 2010 from psychiatric units at an urban public hospital , were r and omized to usual care ( on-unit nicotine replacement plus quit advice ) or intervention , which added a Transtheoretical-model tailored , computer-assisted intervention , stage-matched manual , brief counseling , and 10-week post-hospitalization nicotine replacement . RESULTS The sample ( N = 100 , 69 % recruitment rate , age M = 40 ) was 56 % racial/ethnic minority , 65 % male , 79 % unemployed , and 48 % unstably housed , diagnosed with unipolar ( 54 % ) and bipolar ( 14 % ) depression and psychotic disorders ( 46 % ) ; 77 % reported past-month illicit drug use . Prior to hospitalization , participants averaged 19 ( SD = 11 ) cigarettes/day for 23 ( SD = 13 ) years ; 80 % smoked within 30 minutes of awakening ; 25 % were preparing to quit . Encouraging and comparable to effects in the general population , 7-day point prevalence abstinence for intervention versus control was 12.5 % versus 7.3 % at 3 months , 17.5 % versus 8.5 % at 6 months , and 26.2 % versus 16.7 % at 12 months . Retention exceeded 80 % over 12 months . The odds of abstinence increased over time , predicted by higher self-efficacy , greater perceived social status , and diagnosis of psychotic disorder compared to unipolar depression . CONCLUSIONS Findings indicate uninsured smokers with serious mental illness can engage in tobacco treatment research with quit rates comparable to the general population . A larger investigation is warranted . Inclusion of diverse smokers with mental illness in clinical trials is supported and encouraged OBJECTIVES Using a brief contact control , we tested the efficacy of a staged care intervention to reduce cigarette smoking among psychiatric patients in outpatient treatment for depression . METHODS We conducted a r and omized clinical trial that included assessment s at baseline and at months 3 , 6 , 12 , and 18 . Three hundred twenty-two patients in mental health outpatient treatment who were diagnosed with depression and smoked > or = 1 cigarette per day participated . The desire to quit smoking was not a prerequisite for participation . Staged care intervention participants received computerized motivational feedback at baseline and at 3 , 6 , and 12 months and were offered a 6-session psychological counseling and pharmacological cessation treatment program . Brief contact control participants received a self-help guide and referral list of local smoking-treatment providers . RESULTS As we hypothesized , abstinence rates among staged care intervention participants exceeded those of brief contact control participants at months 12 and 18 . Significant differences favoring staged care intervention also were found in occurrence of a quit attempt and stringency of abstinence goal . CONCLUSION The data suggest that individuals in psychiatric treatment for depression can be aided in quitting smoking through use of staged care interventions and that smoking cessation interventions used in the general population can be implemented in psychiatric outpatient setting OBJECTIVE To describe the design , implementation , baseline data , and feasibility of establishing a disease management program for smoking cessation in rural primary care . METHOD The study is a r and omized clinical trial evaluating a disease management program for smoking cessation . The intervention combined pharmacotherapy , telephone counseling , and physician feedback , and repeated intervention over two years . The program began in 2004 and was implemented in 50 primary care clinics across the State of Kansas . RESULTS Of eligible patients , 73 % were interested in study participation . 750 enrolled participants were predominantly Caucasian , female , employed , and averaged 47.2 years of age ( SD=13.1 ) . In addition to smoking , 427 ( 57 % ) had at least one additional major risk factor for cardiovascular disease ( diabetes , hypertension , high cholesterol , heart disease or stroke ) . Participants smoked on average 23.7 ( SD=10.4 ) cigarettes per day , were contemplating ( 61 % ) or preparing to quit ( 30 % ) , were highly motivated and confident of their ability to quit smoking , and reported seeing their physicians multiple times in the past twelve months ( Median=3.50 ; Mean=5.48 ; SD=6.58 ) . CONCLUSION Initial findings demonstrate the willingness of patients to enroll in a two-year disease management program to address nicotine dependence , even among patients not ready to make a quit attempt . These findings support the feasibility of identifying and enrolling rural smokers within the primary care setting Patterns of smoking cessation using 6- and 12-month follow-up data are reported for 1,261 primary care patients r and omized to 3 physician-delivered smoking interventions : advice only ( AO ) , counseling ( CI ) , and counseling plus availability of nicotine-containing gum ( CI + NCG ) . One-week-point-prevalence cessation rates at 12 months did not differ among the interventions : AO ( 15.2 % ) , CI ( 12.9 % ) and CI + NCG ( 16.7 % ) . However , maintained cessation rates ( abstinent at both 6 and 12 months ) increased with intervention intensity : AO ( 6.0 % ) , CI ( 7.8 % ) and CI + NCG ( 10.0 % ) : Test of trend chi 2 = 5.06 , p = .02 . CI + NCG was significantly higher than AO ( p = .02 ) . The findings support the following conclusions : Brief physician-delivered intervention with availability of nicotine-containing gum can have a beneficial long-term effect on smoking cessation , and cohort data as well as point-prevalence rates are important when assessing the long-term impact of lifestyle interventions INTRODUCTION Persons with a mental disorder smoke at higher rates and suffer disproportionate tobacco-related burden compared with the general population . The aim of this study was to determine if a smoking cessation intervention initiated during a psychiatric hospitalization and continued postdischarge was effective in reducing smoking behaviors among persons with a mental disorder . METHODS A r and omized controlled trial was conducted at an Australian inpatient psychiatric facility . Participants were 205 patient smokers allocated to a treatment as usual control ( n = 101 ) or a smoking cessation intervention ( n = 104 ) incorporating psychosocial and pharmacological support for 4 months postdischarge . Follow-up assessment s were conducted at 1 week , 2 , 4 , and 6 months postdischarge and included abstinence from cigarettes , quit attempts , daily cigarette consumption , and nicotine dependence . RESULTS Rates of continuous and 7-day point prevalence abstinence did not differ between treatment conditions at the 6-month follow-up ; however , point prevalence abstinence was significantly higher for intervention ( 11.5 % ) compared with control ( 2 % ) participants at 4 months ( OR = 6.46 , p = .01 ) . Participants in the intervention condition reported significantly more quit attempts ( F[1 , 202.5 ] = 15.23 , p = .0001 ) , lower daily cigarette consumption ( F[4 , 586 ] = 6.5 , p < .001 ) , and lower levels of nicotine dependence ( F[3 , 406 ] = 8.5 , p < .0001 ) compared with controls at all follow-up assessment s. CONCLUSIONS Postdischarge cessation support was effective in encouraging quit attempts and reducing cigarette consumption up to 6 months postdischarge . Additional support strategies are required to facilitate longer-term cessation benefits for smokers with a mental disorder This study , which tested two motivational interviewing treatment approaches , assessed the feasibility of conducting a community-based smoking cessation intervention among homeless smokers . Participants ( N = 46 ) were recruited from multiple facilities in the Kansas City area and were r and omized to two counseling conditions in which they received five individual motivational interviewing sessions , six group meetings , and their choice of 8 weeks of 21-mg nicotine patch or 4-mg nicotine lozenge . The two counseling conditions consisted of motivational interviewing targeted either to smoking behaviors exclusively ( smoking only ) or to smoking and other addictions or life events that could affect ability to quit ( smoking plus ) . Group meetings were design ed to provide educational information and social support . Measures of feasibility assessed included the proportion of participants who returned for r and omization among those eligible , adherence to prescribed nicotine replacement therapies , retention rates at the week 26 final study visit , and biochemically verified 7-day abstinence at week 26 . Most participants ( 69.6 % ) chose nicotine patches , and 32 % of those participants reported using at least four patches per week . Carbon monoxide verified 7-day abstinence rates in the smoking-only and smoking-plus groups were 13.04 % and 17.39 % ( ns ) , respectively , at week 8 and 8.70 % and 17.39 % ( ns ) , respectively , at week 26 . Participants who used at least four patches per week were more likely to have quit at 8 weeks than were those who used fewer patches ( 33.3 % vs. 10.5 % , p = .30 ) . Results support the feasibility of conducting a smoking cessation intervention among homeless smokers . Findings also show promising effects for nicotine replacement therapy and counseling in this population . Developing programs to improve smoking cessation outcomes in underserved population s is an essential step toward achieving national health objectives and for ultimately reducing tobacco-related health disparities OBJECTIVES Transdermal nicotine patches have shown considerable promise in improving smoking cessation outcomes . The present study assessed telephone support as an adjunct to a managed care-based , single-session group orientation smoking cessation program with nicotine patch therapy . METHODS The unit of r and omization was the orientation session ( n = 35 ) . Subjects ( n = 509 ) were r and omly assigned to a group session without telephone support , the session plus access to a toll-free help line , or the session with telephone help line plus active telephone outreach . RESULTS Contrary to hypothesis , there were no differences between treatment conditions . Overall abstinence rates were 22 % at 6 months and 21 % at 1 year . Fewer than 1 % of eligible subjects called the toll-free help line . An average of 3.8 of a possible 4 calls were completed in the telephone outreach condition . CONCLUSIONS Abstinence results obtained in this program were comparable to those obtained with more extensive counseling . However , there was no evidence of benefit from telephone support beyond the initial physician-led group orientation session Purpose : The purpose of this study was to investigate the effects of a cognitive behavioral therapy – oriented anger management and stress control program on smokers ' quit rates . Methods : Of 2348 smokers , 350 were r and omly allocated into study and control groups ( n = 175 each ) . An individualized therapy cessation technique was selected for each participant ( combination of behavioral counseling , nicotine replacement therapy , and /or pharmacotherapy ) . The participants in the control group attended a st and ard quit program , whereas the study group also received an additional 5-session ( 90 minutes each ) cognitive behavioral therapy – oriented program aim ed at improving their anger and stress coping skills . At the beginning of the study , both groups were asked to complete the Trait Anger Scale ( TAS ) of the State and Trait Anger Scale and the Self-Confident ( SCS ) and Hopeless ( HS ) subscales of the Stress Coping Styles Inventory ; pretest smoking status of both groups and their coping skills were compared with each other as soon as the program ended ( post-test results ) and after 3 and 6 months ( first and second follow-up tests ) . Results : Although there was no difference between pretest scores on the TAS ( P = .234 ) , SCS ( P = .130 ) , and HS ( P = .148 ) subscales , post-test results indicate that the study groups ' TAS and HS scores decreased and SCS scores increased ( P < .001 ) , whereas there was no change in the control group ( P > .05 ) . The study group had a better quit level after 6 months compared with the control group ( 44 % vs 27.4 % ; P < .001 ) . The anger management and stress control program was found to have a significant effect on cessation ( odds ratio , 2.09 ; 95 % confidence interval , 1.14–3.85 ) . Conclusion : The anger and stress coping skills program may increase the success of quitting smoking BACKGROUND We tested the role of nicotine-containing gum ( NCG ) in conjunction with brief physician counseling in smoking cessation in the Physician-Delivered Smoking Intervention Project ( PDSIP ) . METHOD Subjects were smokers r and omized to the Counseling + NCG arm of the PDSIP . However , receipt and use of NCG were not r and omized . Data from base-line , were not r and omized . Data from baseline , pharmacy records , and 6-month monitoring calls were used in these post hoc analyses . RESULTS Of the 299 study subjects , 57 % accepted NCG and 36 % of acceptors used it for more than 7 days . Predictors of NCG acceptance included high desire to quit ( OR = 1.21 ; 95 % CI 1.10 , 1.35 ) , social support to quit ( OR = 1.62 ; 95 % CI 1.01 , 2.59 ) , being a general medicine patient compared with a family practice patient ( OR = 3.22 ; 95 % CI 2.01 , 5.21 ) , and receiving the intervention from a female physician ( female physician-male patient OR = 2.27 ; 95 % CI 0.95 , 5.46 ; female physician-female patient OR = 1.94 ; 95 % CI 1.06 , 3.57 ) relative to the male physician comparisons . Subjects who refilled the NCG prescription had higher cessation rates than those who did not refill or did not accept the prescription ( 37 % vs 19 % and 20 % , respectively ; P = 0.04 ) . Predictors of 6-month cessation among NCG users included a previous period(s ) of abstinence > 3 months ( OR = 1.23 ; 95 % CI 1.04 , 1.47 ) , abstinence during illness ( OR = 0.39 ; 95 % CI 0.17 , 0.86 ) , and absence of smoking-related physical complaints the month prior to the physician-delivered intervention ( OR = 0.40 ; 95 % CI 0.17 , 0.94 ) . CONCLUSION Amount of NCG use in conjunction with physician-delivered smoking cessation counseling might have contributed in helping unselected smokers quit OBJECTIVES To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release ( SR ) in combination with behavioral interventions of minimal intensity ( tailored mailings [ TM ] ) or moderate intensity ( proactive telephone calls [ PTC ] ) for smoking cessation in an actual practice setting . STUDY DESIGN Open-label , r and omized trial , with 1-year follow-up , conducted in a large health system based in Seattle , Washington . METHODS A total of 1524 adult smokers interested in quitting smoking were r and omly assigned to receive 150 mg bupropion SR daily and PTC ( n = 382 ) , 150 mg bupropion SR daily and TM ( n = 381 ) , 300 mg bupropion SR daily and PTC ( n = 383 ) , or 300 mg bupropion SR daily and TM ( n = 378 ) . Sufficient medication for 8 weeks of dosing was provided to patients . The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date . RESULTS Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM , the additional cost result ed in lower cost effectiveness . The PTC behavioral intervention was more expensive than TM , but the additional effectiveness result ed in almost equivalent cost effectiveness at the 150-mg dose . Costs per additional 12-month nonsmoker ( above that expected for placebo ) for the 150-mg dose groups averaged 950 dollars and per additional lifetime quitter averaged 1508 dollars ; for the 300-mg groups these costs were 1342 dollars and 2129 dollars , respectively . Cost per life-year and quality -adjusted life-years ( QALYs ) saved varied substantially by age and treatment , but were no greater than 1100 dollars for all treatment groups when averaged across the age and sex distribution for the study population . CONCLUSIONS Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments , within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective AIMS To examine heterogeneity in outcome following treatment for smoking cessation with combined bupropion SR and behavioral counseling in women and men . DESIGN , SETTING , PARTICIPANTS This study included 875 women and 649 men recruited from a large health-care system and r and omized to one of four combinations of treatment [ two dosage levels of bupropion SR ( Zyban , 150 mg and 300 mg ) were crossed with two counseling programs of lower and higher intensity to create a four-cell design ] . MEASUREMENTS AND FINDINGS A comprehensive set of relevant individual characteristics prior to treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified six subgroups in women that ranged in proportion of non-smokers from 9.8 % to 42.9 % and six subgroups in men that ranged in proportion of non-smokers from 17.3 % to 50.0 % . CONCLUSIONS These results indicate the presence of a substantial amount of variation in treatment outcome among women and men receiving combined bupropion SR and counseling . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following cessation OBJECTIVE Fear of jeopardizing drinking outcomes has result ed in a reluctance to treat tobacco dependence concurrently with alcohol dependence , in spite of the high prevalence of smoking among patients with alcohol dependence . The objective of this study was to compare the effects of smoking treatment and intensive treatment for alcohol dependence , delivered concurrently , with delayed smoking treatment on smoking and alcohol use . METHOD For the study , 1,943 patients in intensive treatment for alcohol dependence or abuse were screened for participation . Of these , 499 smokers were enrolled and r and omized to concurrent ( during alcohol treatment ) or delayed ( 6 months later ) smoking intervention . The smoking intervention included individual behavioral counseling and nicotine replacement . The main smoking outcome measure was 7-day point prevalent tobacco abstinence , and the main drinking outcome was 6-month prolonged abstinence from alcohol ; both measured 18 months after study enrollment . RESULTS Participants in the concurrent group were more likely to participate in smoking treatment than those in the delayed group ( 78.5 % vs 64.5 % , p = .005 ) , but there was no significant difference in cessation rates at 18 months ( 12.4 % vs 13.7 % ) . Prolonged , 6-month abstinence from alcohol was worse in the concurrent group than in the delayed group at 6 , 12 and 18 months ( 41 % vs 56 % , p = .001 ; 33 % vs 42%,p = .06 ; 41 % vs 48 % , p = .14 , respectively ) , and 30-day prolonged alcohol abstinence was also worse in the concurrent treatment group ( 51 % vs 64 % , p = .004 ; 46 % vs 53 % , p = .11 ; 48 % vs 60 % , p = .01 , respectively ) . CONCLUSIONS These data show that patients in alcohol treatment are interested in smoking cessation , participate in treatment and demonstrate success ; but there was no benefit of concurrent treatment . Drinking outcomes were worse with concurrent tobacco treatment . These findings suggest that smoking cessation intervention should be provided to patients after intensive alcohol treatment ; however , the data require confirmation because they are not consistent with the existing literature Individuals with mental illness and co-occurring addictive disorders account for 44 % of the cigarettes sold in the United States ( JAMA 284:2606–2610 , 2000 ) . Smokers with mental illness face serious tobacco-related consequences , including increased morbidity and mortality , isolation , stigma , and financial hardship . Tobacco use also increases the metabolism of some antipsychotic and antidepressant medications , with the potential for subtherapeutic treatment and higher rates of rehospitalization . Nearly half of U.S. state psychiatric hospitals now ban tobacco use on their premises . The American Psychiatric Association identifies psychiatric hospitalizations as an ideal opportunity to treat tobacco dependence . Yet little research has examined tobacco cessation treatments in inpatient psychiatry . If tobacco dependence is left unaddressed , most psychiatric patients return to smoking immediately after discharge ( American Journal of Addictions 15:15–22 , 2006 ) . Multi-component interventions are needed that address the motivational , behavioral , and physiological aspects of nicotine dependence for smokers with co-occurring psychiatric disorders . We briefly describe an innovative tobacco treatment intervention initiated during psychiatric hospitalization . The intervention combines a computer-delivered expert system intervention and manual based on the transtheoretical model , an individual counseling session , and nicotine replacement therapy ( NRT ) . The model identifies five stages of change : precontemplation ( no immediate intention to stop smoking ) , contemplation ( intending to quit in the next six months ) , preparation ( considering quitting in the next month with a quit attempt in the past year ) , action ( quit smoking for less than six months ) , and maintenance ( smoke-free for at least six months ) . The 20-minute computer intervention generates individualized feedback at a sixth- grade reading level to guide participants through the stages of quitting smoking and to direct them to relevant sections of the manual . In a 30-minute session with the participant , study counselors review the printed feedback and manual , identify and support goals concerning tobacco use , and discuss proper use of NRT . Nine hospitalized psychiatric patients representing a range of psychiatric , demographic , and tobacco-use characteristics intensively evaluated the intervention components . Despite having fairly limited computer experience , all agreed or strongly agreed that the program was easy to underst and and gave sound advice , and all recommended the computer program to others . Most participants required assistance with program navigation , suggesting the need for more user-friendly capabilities , such as a touch screen and audio . All participants read part of the manual , and most read beyond their stage-of-change chapter . Participants rated the manual highly for its organization and helpful strategies , describing it as “ realistic ” and “ easy to underst and … good for any person to read . ” Participants also rated the counseling session highly , citing the openness of the dialogue , the focus on their needs and interests , and the lack of pressure to quit : “ She did n’t push any points … she just presented the material . She was open , nonjudgmental . … She let me come to my own conclusions that I want to quit . ” Most participants used NRT , identified several benefits , and expressed interest in continuing NRT after hospitalization . Side effects also were noted . Of concern , most participants stated that clinical staff did not instruct them in proper use of NRT . This small and intensive evaluation suggests that the intervention provides a viable and acceptable strategy for initiating tobacco treatment in the inpatient psychiatric setting . In a r and omized clinical trial , we are evaluating efficacy of the intervention relative to usual care . With a 79 % recruitment rate , we enrolled 224 participants . After the brief hospital stay , intervention participants received ten weeks of NRT and two additional computer contacts , and their outpatient providers were informed of their cessation goals . Follow-up continues for 18 months . Psychiatric hospitals are making important strides in banning tobacco use . Bans , however , are only part of a much larger strategy needed to overcome the high rates of tobacco use in population s with mental illness . If cessation services are not offered , patients may misperceive smoking bans as punitive and themselves as unworthy of receiving intervention on this deadly addiction . When smoking was allowed on psychiatric units , an average of 15 minutes was spent per nursing shift managing patients ’ cigarette use . Ideally , a portion of the time saved with a no-smoking policy could be shifted to delivery of cessation services . The findings present an innovative , acceptable , multicomponent intervention for initiating tobacco treatment in inpatient psychiatry INTRODUCTION Tobacco use is a serious public health problem among low-income Chinese Americans with limited English proficiency . Chinese men are at high risk for smoking-related morbidity and mortality . We tested the feasibility of a culturally and linguistically sensitive smoking intervention program with combined counseling and pharmacological components for Chinese smokers in New York City ; identified factors and techniques that enhance the administration and appropriateness of the intervention program ; and examined the overall impact of this program on quit attempts , quit rates , and overall smoking reduction . METHODS We were guided by the transtheoretical model and used an adapted motivational interviewing ( MI ) approach . The study involved a r and omized sample with pretreatment assessment and multiple follow-up measures . Eligible participants ( N = 122 ) were r and omly assigned to intervention ( 4 individualized counselor-led MI sessions and nicotine replacement therapy [ NRT ] ) or control groups ( 4 general health education sessions , self-help material s , and NRT ) . RESULTS Quit rate at 6 months in the intervention group was 67 % versus 32 % for the control group , indicating minimal relapse and a highly successful intervention program . Increase in self-efficacy and decease in pros of smoking from baseline to 6-month follow-up were positively associated with smoking cessation . The number of cigarette smoked at baseline was inversely related to smoking cessation . Results indicate that a combined intensive behavioral counseling and pharmacological intervention can reduce smoking substantially . CONCLUSION The results of this pilot will be used as a basis for a large-scale r and omized trial of an intervention with combined culturally and linguistically sensitive MI and NRT components for Chinese and other Asian ethnic groups To date , only one study has been published on individual characteristics associated with outcome following st and ard treatment with bupropion SR for smoking cessation . To investigate treatment outcome beyond the 6-week end-of-treatment point , the present study examined characteristics associated with more clinical ly relevant smoking endpoints following treatment with bupropion SR in a large health care system . A total of 1,524 smokers ( 649 men and 875 women ) of average age 45.1 years were r and omized to receive one of four combinations of bupropion SR ( 150 or 300 mg ) and behavioral counseling ( tailored mailings or proactive telephone counseling ) and assessed for point-prevalent smoking status at 3 and 12 months . Multiple logistic regression analyses of potential risk factors for 12-month point-prevalent smoking and for persistent smoking ( point-prevalent smoking at both follow-ups ) following treatment were conducted for men and women combined and separately . Risk factors for smoking at both endpoints in the combined sample included treatment with tailored mailings , female gender , younger age , higher levels of tobacco dependence , shorter previous quit attempts , previous use of nicotine replacement therapy , and report of current depressive symptoms or lifetime depression . Risk factors for smoking following treatment identified in women only included treatment with the lower dose of bupropion SR , younger age , and higher perceived stress , whereas those that were unique to men included the presence of lifetime depression . The results are discussed in terms of their implication s for the need for more effective treatments in general , and the role of individual differences in the likelihood of returning to smoking following treatment for quitting BACKGROUND The authors evaluated the incremental efficacy of telephone counselling by a nurse in addition to physician advice and nicotine replacement therapy in helping patients to stop smoking . METHODS The trial was conducted at the University of Ottawa Heart Institute . A total of 396 volunteers who smoked 15 or more cigarettes daily were r and omly assigned to either of 2 groups : usual care ( control group ) and usual care plus telephone counselling ( intervention group ) ; the groups were stratified by sex and degree of nicotine dependence . Usual care involved the receipt of physician advice on 3 occasions , self-help material s and 12 weeks of nicotine replacement therapy . Telephone counselling was provided by a nurse at 2 , 6 and 13 weeks after the target quit date . Point-prevalent quit rates were determined at 52 weeks after the target quit date . RESULTS The point-prevalent quit rates at 52 weeks did not differ significantly between the control and intervention groups ( 24.1 % v. 23.4 % respectively ) . The quit rates did not differ significantly at the secondary measurement points of 4 , 12 and 26 weeks . INTERPRETATION Brief physician assistance , along with nicotine replacement therapy , can help well-motivated smokers to quit . Three additional sessions of telephone counselling by a nurse were ineffective in increasing quit rates . This form of assistance may be useful in the absence of physician advice or when self-selected by patients OBJECTIVE Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs , few studies have investigated the efficacy of smoking cessation interventions among this group . The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone . METHOD The authors recruited 298 regular smokers with a psychotic disorder residing in the community and r and omly assigned them to a routine care comparison condition ( N=151 ) or an eight-session , individually administered smoking cessation intervention ( N=147 ) , which consisted of nicotine replacement therapy , motivational interviewing , and cognitive behavior therapy . Outcome variables included continuous and point-prevalence abstinence rates , smoking reduction status , and changes in symptoms and functioning . RESULTS While there were no overall differences between the treatment group and comparison group in abstinence rates , a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions ( point-prevalence rates : 3 months , 30.0 % versus 6.0 % ; 6 months , 18.6 % versus 4.0 % ; and 12 months , 18.6 % versus 6.6 % ) . Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months ( 21.4 % versus 4.0 % ) . There was a strong dose-response relationship between treatment session attendance and smoking reduction status , with one-half of those who completed the intervention program achieving a 50 % or greater reduction in daily cigarette consumption across the follow-ups , relative to less than one-fifth of the comparison subjects . There was no evidence of any associated deterioration in symptoms or functioning . CONCLUSIONS These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder . Further development of more efficacious interventions is required for those who do not respond to existing interventions The study evaluated the efficacy of the Committed Quitters Program ( CQP ) , a computer-tailored set of printed behavioral support material s offered free to purchasers of NicoDerm CQ patches , as a supplement to the nicotine patch and the st and ard brief User 's Guide ( UG ) and audiotape . Callers to the CQP enrollment were r and omized to either CQP ( n=1854 ) or just the UG ( n=1829 ) . Abstinence and use of program material s were assessed by telephone interview at 6 and 12 weeks ( the latter falling 2 weeks after patch use was to be discontinued ) . Considering all respondents , abstinence rates did not differ significantly between the UG and CQP groups . As expected , among those who reported they used their assigned material s ( 80.1 % of the sample ) smokers who received CQP demonstrated higher quit rates at both 6 weeks ( 38.8 % v. 30.7 % ) and 12 weeks ( 18.2 % v. 11.1 % ) , compared to the UG group . Among those who used it , the Committed Quitters Program proved to be an effective behavioral treatment , improving quit rates over nicotine replacement therapy and a brief untailored written guide and audiotape Context Smoking cessation is difficult and may require repeated or intensive interventions . Contribution In this multicenter trial , 750 primary care patients who smoked at least 10 cigarettes per day were r and omly assigned to pharmacotherapy ( nicotine patch or bupropion ) , pharmacotherapy supplemented with up to 2 calls from trained counselors , or pharmacotherapy supplemented with up to 6 counseling calls . Utilization of the interventions , which were offered every 6 months for 2 years , declined over time . Smoking abstinence rates at 2 years were 23 % , 24 % , and 28 % in the 3 groups . Caution Pharmacotherapy was free . Smoking abstinence was self-reported . The Editors Cigarette smoking is a chronic illness characterized by repeated cycles of quit attempts and relapse . Most models for addressing smoking cessation are based on single , short-term interventions lasting only a few weeks or months ( 1 ) . Although most smokers will not quit after a single intervention , few studies have addressed the chronic nature of nicotine dependence by providing systematic , repetitive treatment opportunities ( 1 ) . Providing treatment only to smokers who are already prepared to quit further limits the reach of current smoking cessation interventions ( 2 ) . New models of chronic disease care might provide an alternative approach for exp and ing the reach and effectiveness of smoking cessation efforts ( 3 ) . Physicians are in direct contact with approximately 70 % of smokers each year ( 4 , 5 ) . Their potential role in promoting smoking cessation has been well delineated and incorporated into current clinical practice guidelines ( 1 ) . With the development of new , more effective prescription pharmacotherapy for smoking cessation , the role of primary care practice s in promoting smoking cessation is now more important than ever . Unfortunately , only half of the smokers who see their physicians are asked about their smoking ( 6 ) , and even fewer receive advice from their health care provider to quit or receive pharmacotherapy or follow-up ( 4 , 7 ) . Smoking cessation counseling competes with other pressing clinical tasks , and beyond brief advice , many physicians feel they are too busy to routinely and repeatedly counsel participants who smoke ( 810 ) . To assist primary care physicians in the treatment of rural smokers , we developed KanQuit , a smoking cessation program based on the chronic care model ( 4 ) , which integrates principles of disease management into the treatment of smokers seen in rural primary care . Our objective was to enroll smokers , regardless of their willingness to quit , into a disease registry and compare cessation rates among smokers who received pharmacotherapy alone or combined with either moderate-intensity or high-intensity disease management that includes counseling and provider feedback . Methods Design Overview We did a r and omized , single-blind trial of varying levels of disease management for smoking cessation . We recruited participants who smoked more than 10 cigarettes per day from rural primary care clinics across Kansas and r and omly assigned them to receive pharmacotherapy alone , pharmacotherapy supplemented by 1 to 2 counseling calls every 6 months ( moderate-intensity disease management ) , or pharmacotherapy supplemented by up to 6 counseling calls every 6 months ( high-intensity disease management ) . For recipients of moderate-intensity and high-intensity disease management , we faxed periodic progress reports to their physician . We offered all participants free pharmacotherapy ( either bupropion or transdermal nicotine patch ) every 6 months . We enrolled participants from June 2004 to October 2005 and followed them for 24 months , completing follow-up in December 2007 . All participants provided written informed consent . The University of Kansas Medical Center 's Human Subjects Committee approved the study . Setting and Participants We conducted our study in 50 rural primary care practice s in the Kansas Physicians Engaged in Prevention Research network ( 11 ) . As part of a rural primary care research experience , trained medical students systematic ally screened participants , identified smokers , and recruited them for this study , regardless of their interest in quitting ( 12 ) . We considered smokers eligible if they had a primary care physician who participated in this study ; were older than 18 years ; smoked more than 10 cigarettes per day for at least 1 year and for at least 25 of the past 30 days ; spoke English ; and had a telephone . We excluded smokers if they were pregnant or planned to become pregnant , planned to move out of the study area , had signs of dementia or mental illness that would preclude participation , or lived with a smoker already enrolled in the study . Of the 1827 smokers we screened , 61 % met criteria for study entry ( Figure 1 ) . Of these , we enrolled 67 % . Figure 1 . Study flow diagram . HDM = high-intensity disease management ; MDM = moderate-intensity disease management ; PM = pharmacotherapy management . R and omization and Interventions Participant R and omization R and omization occurred at the participant level . A computer-generated r and om-number table was used to generate allocation cards in blocks of 24 , with allocation equally distributed across treatment groups . To conceal allocation , we placed these cards in sequentially numbered , opaque , sealed envelopes . After research assistants verified participant eligibility and completed the baseline assessment , the project director opened the next sequential sealed envelope and determined the participant 's treatment allocation . One of 9 counselors trained in smoking cessation and motivational interviewing ( 12 ) conducted all interventions from a single central site . We assigned participants to counselors without regard to practice site . Pharmacotherapy At baseline , all smokers received a health education mailing that consisted of a welcome letter , information about the use of bupropion and the nicotine patch for smoking cessation , and copies of You Can Quit Smoking : Consumer Guide ( 13 ) and When Smokers QuitThe Health Benefits Over Time ( 14 ) . At baseline and at 6 , 12 , and 18 months , participants received a mailed offer for free pharmacotherapy that consisted of either a 6-week course of a nicotine patch ( 21 mg/d ) or a 7-week course of sustained-release bupropion ( 150 mg twice daily ) . Participants interested in using either medication could return a postage-paid postcard or call a toll-free number . We screened all participants who requested pharmacotherapy for potential contraindications ( 15 ) . Participants with absolute contraindications for a given drug were ineligible to receive that drug but were offered the option of receiving the other drug . Participants with contraindications to both drugs were not eligible to receive medication from the study but could participate in all other aspects of the intervention . For participants who requested bupropion and those with relative contraindications to the nicotine patch , research staff faxed a prescription request to their primary care physicians . This prescription request delineated any relative contraindications or potential drug interactions . For these participants , their physicians made the final assessment of the appropriateness of the bupropion or the patch . For participants without contraindications to the nicotine patch or on receipt of a faxed , signed prescription , the bupropion or patches were mailed to the participant along with instructions for use . Disease Management In addition to pharmacotherapy , the moderate-intensity and high-intensity disease management groups received educational support , telephone counseling , and periodic progress reports with counseling suggestions faxed to their physician . Every 6 months , they received a KanQuit newsletter that addressed tips on quitting smoking , talking with their physician about smoking , and using pharmacotherapy for cessation . The newsletters were personalized to include study up date s , counselor photographs , physician feature stories , and testimonials of participants who had quit smoking . We offered participants assigned to moderate-intensity disease management up to 2 telephone-based counseling sessions every 6 months ( 1 session to promote a quit attempt and 1 additional follow-up session for those who made a quit attempt ) . We offered participants assigned to high-intensity disease management up to 6 counseling calls every 6 months to either promote quitting or prevent relapse . We scheduled calls at the participant 's convenience , and they varied according to the participant 's quit plan but followed a rough schedule of calls at 1 , 3 , 6 , 9 , and 16 weeks after the onset of each 6-month treatment cycle . Counselors used motivational interviewing techniques and followed a semistructured protocol to promote a cessation attempt or , for abstinent smokers , to encourage relapse prevention . During counseling calls , case managers reminded participants about the availability of pharmacotherapy and , for interested participants , provided immediate support for acquiring either the nicotine patch or bupropion , as described previously . We faxed personalized progress reports with suggestions for interventions to the participant 's physician after the first counseling call ( both moderate-intensity and high-intensity disease management participants ) and after the last counseling call ( high-intensity disease management participants only ) during each 6-month cycle . We faxed additional progress reports to the participant 's physician whenever the moderate-intensity or high-intensity disease management participant set a quit date . Outcomes , Measurements , and Follow-up Research assistants who were blinded to treatment group assignment conducted assessment s by telephone at baseline and at 6 , 12 , 18 , and 24 months . Primary Outcome The primary outcome measure was self-reported 7-day abstinence at 24 months , defined as not having smoked a cigarette during the previous 7 days . Although self-reported abstinence has been Abstract Aim : To examine heterogeneity in outcome at 12 months following 8 weeks of treatment for smoking cessation with bupropion sustained-release ( SR ) 150 or 300 mg/day combined with behavioural counselling . Design , setting , participants : Smokers were recruited from a large healthcare system and then r and omized to receive either bupropion SR 150 mg/day ( n = 763 ) or 300 mg/day ( n = 761 ) taken for 8 weeks in combination with either proactive telephone counselling or a tailored mail approach . Measurements and findings : A comprehensive set of relevant individual pre-treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular self-reported smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified subgroups that varied with respect to likelihood of being nonsmokers at 12 months . Seven subgroups were identified among those receiving bupropion SR 150 mg/day ( proportion of nonsmokers at 12 months ranged from 13.7 % to 43.5 % ) and eight subgroups among those receiving bupropion SR 300 mg/day ( proportion of nonsmokers at 12 months ranged from 9.6 % to 51.7 % ) . In the 150-mg/day group , those with the lowest rate reported no previous quit attempt of 1 month or more in duration while those with the highest rate all reported previous quit attempts of 1 month or longer . In the 300 mg/day group , those with the lowest rate had very high levels of dependence while those with the highest rate were more highly educated and smoked at a lower level . Across all subgroups , cost per 12-month quitter ranged from a low of $ US302 to a high of $ US2502 . Conclusions : These results indicate the presence of a substantial amount of variation in outcome following treatment with both dosages of bupropion SR , with substantial cost consequences . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following a quit attempt OBJECTIVE To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients . METHOD A r and omized , 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012 . Adults meeting DSM-IV-TR criteria for cocaine and /or methamphetamine dependence and interested in quitting smoking were r and omized to treatment as usual ( n = 271 ) or treatment as usual with smoking-cessation treatment ( n = 267 ) . All participants received treatment as usual for substance use disorder treatment . Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion ( 300 mg/d ) during weeks 1 - 10 . During post-quit treatment ( weeks 4 - 10 ) , participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence . Weekly proportion of stimulant-abstinent participants during the treatment phase , as assessed by urine drug screens and self-report , was the primary outcome . Secondary measures included other substance/nicotine use outcomes and treatment attendance . RESULTS There were no significant treatment effects on stimulant-use outcomes , as measured by the primary outcome and stimulant-free days , on drug-abstinence , or on attendance . Participants assigned to treatment as usual with smoking-cessation treatment , relative to those assigned to treatment as usual , had significantly better outcomes for drug-free days at 6-month follow-up ( χ(2)(1 ) = 4.09 , P < .05 ) , with a decrease in drug-free days from baseline of -1.3 % in treatment as usual with smoking-cessation treatment and of -7.6 % in treatment as usual . Participants receiving treatment as usual with smoking-cessation treatment , relative to those receiving treatment as usual , had significantly better outcomes on smoking point-prevalence abstinence ( 25.5 % vs 2.2 % ; χ(2)(1 ) = 44.69 , P < .001 ; OR = 18.2 ) . CONCLUSIONS These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen , and may enhance , abstinence from nonnicotine substance use . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01077024 AIMS This paper sets out to evaluate the possibility that smoking cessation interventions which make use of current psychological theories and constructs can be more successful than programmes based largely on nicotine replacement therapy and will be more satisfying to participants . RATIONALE Nicotine replacement therapy is currently the most widely used method for helping smokers give up the habit . Numerous studies have shown this to be a successful approach for many smokers , but the majority still fail to benefit . Typically three quarters of smokers given nicotine replacement are smoking again one year later . This study investigates whether nicotine replacement can be enhanced by the addition of psychological techniques . DESIGN Smokers recruited via publicity in the local media were r and omly assigned to one of two treatment conditions . The first condition consisted of a series of group sessions in which volunteers were instructed in nicotine replacement , and a number of psychological techniques , the most important being cognitive counter conditioning . The second condition was identical to the first but without the cognitive counter conditioning . Finally background quit rate was determined using waiting list controls . RESULTS Both interventions were successful in helping smokers quit the habit , based upon an analysis at 6 months , compared with waiting list controls . The experimental condition incorporating cognitive counter conditioning produced a much higher quit rate than the condition based largely upon nicotine replacement , although the difference was not significant . CONCLUSIONS This study is highly suggestive that nicotine replacement therapy can be enhanced by the inclusion of psychological techniques in group work , result ing in abstention rates higher than nicotine replacement alone and increasing participant satisfaction . Further work is needed with larger numbers to verify that this is indeed a significant gain and to investigate whether psychological techniques can give longer term benefits STUDY OBJECTIVE Tobacco use is common among emergency department ( ED ) patients , many of whom have low income . Our objective is to study the efficacy of an intervention incorporating motivational interviewing , nicotine replacement , and quitline referral for adult smokers in an ED . METHODS This was a 2-arm r and omized clinical trial conducted from October 2010 to December 2012 in a northeastern urban US ED with 90,000 visits per year . Eligible subjects were aged 18 years or older , smoked , and were self-pay or had Medicaid insurance . Intervention subjects received a motivational interview by a trained research assistant , 6 weeks ' worth of nicotine patches and gum initiated in the ED , a faxed referral to the state smokers ' quitline , a booster call , and a brochure . Control subjects received the brochure , which provided quitline information . The primary outcome was biochemically confirmed tobacco abstinence at 3 months . Secondary endpoints included quitline use . RESULTS Of 778 enrolled subjects , 774 ( 99.5 % ) were alive at 3 months . The prevalence of biochemically confirmed abstinence was 12.2 % ( 47/386 ) in the intervention arm versus 4.9 % ( 19/388 ) in the control arm , for a difference in quit rates of 7.3 % ( 95 % confidence interval 3.2 % to 11.5 % ) . In multivariable logistic modeling controlling for age , sex , and race or ethnicity , study subjects remained more likely to be abstinent than controls ( odds ratio 2.72 ; 95 % confidence interval 1.55 to 4.75 ) . CONCLUSION An intensive intervention improved tobacco abstinence rates in low-income ED smokers . Because approximately 20 million smokers , many of whom have low income , visit US EDs annually , these results suggest that ED-initiated treatment may be an effective technique to treat this group of smokers BACKGROUND The purpose of this study was , to identify predictors of quitting following general practitioners ' ( GP ) anti-smoking counseling . METHODS We studied determinants ( characterized following the Precede framework ) of successful quitting ( 1 year sustained abstinence , biochemically confirmed at 6- and 12-month follow-up ) among 861 smokers r and omized to the intervention groups based on repeated counseling ( RC ) , RC + spirometric testing , and RC + nicotine gum , in a smoking cessation trial carried out in Turin , Italy . RESULTS GPs ' intervention worked best for male ( OR = 2.30 ; 95 % CI , 1.13 - 4.52 ) and married ( OR = 3.63 ; 95 % CI , 1.37 - 9.59 ) smokers , for smokers who had maintained abstinence for at least 1 month in the past ( OR = 6.78 ; 95 % CI , 1.56 - 29.52 ) or at their first quit attempt ( OR = 10.91 ; 95 % CI , 2.37 - 50.13 ) , and for those who spontaneously reduced their coffee consumption ( OR = 3.30 ; 95 % CI , 1.59 - 6.82 ) ; heavy smokers ( > = 20 cig/day OR = 0.48 ; 95 % CI , 0.24 - 0.93 ) and those living with other smokers ( > = 1 smokers in the household : OR = 0.44 ; 95 % CI , 0.22 - 0.90 ) were less likely to give up . Previous antismoking advice by the GP represented a strong barrier to success for healthy smokers ( OR = 0.19 ; 95 % CI , 0.07 - 0.52 ) , but not for those reporting symptoms of shortness of breath ( OR = 0.63 ; 95 % CI , 0.39 - 9.20 ) . There were no interactions between predictors and treatment conditions . CONCLUSIONS Assessment of factors influencing quitting would allow GPs to tailor their message to address existing barriers and to help patients utilize their re sources for change PURPOSE S To compare an intensive smoking cessation intervention against usual care in hospitalized high-risk smokers with acute cardiovascular disease . METHODS A total of 209 hospitalized smokers were r and omized to the intensive intervention ( n = 109 ) or to usual care ( n = 100 ) . Usual care consisted only of counseling and printed educational material provided prior to hospital discharge . Intensive treatment consisted of a minimum of 12 weeks of behavior modification counseling and individualized pharmacotherapy provided at no cost to the participant . Smoking status in all subjects was confirmed biochemically ( ie , by measuring expired carbon monoxide ) at 3 , 6 , 12 , and 24 months after r and omization . Outcomes included point prevalence and continuous abstinence smoking cessation rates , hospitalizations , and all-cause mortality . RESULTS At each follow-up interval , point prevalence and continuous abstinence smoking cessation rates were significantly greater in the intensive-treatment group compared to the usual-care group . At 24 months , continuous abstinence smoking cessation rates were 33 % in the intensive-treatment group and 9 % in the usual-care group ( p < 0.0001 ) . Over the 2-year follow-up period , 41 patients in the usual-care group were hospitalized compared to 25 patients in the intensive-treatment group ( relative risk reduction [ RRR ] , 44 % ; 95 % confidence interval [ CI ] , 16 to 63 % ; p = 0.007 ) . The all-cause mortality rate was 2.8 % in the intensive-treatment group and 12.0 % in the usual-care group ( RRR , 77 % ; 95 % CI , 27 to 93 % ; p = 0.014 ) . The absolute risk reduction in mortality was 9.2 % with a number needed to treat of 11 . CONCLUSION Hospitalized smokers , especially those with cardiovascular disease , should undergo treatment with a structured intensive cessation intervention . The duration of the initial treatment should be 3 months The purpose of this pilot study was to examine the effectiveness of an 8-week , nurse-managed , peer-led smoking cessation intervention among HIV-positive smokers . The intervention was based on the Agency for Health Care Policy and Research Smoking Cessation Clinical Practice Guideline and was delivered by an ex-smoker who was HIV positive and had been trained by an advanced practice nurse to deliver cessation counseling . Eight male HIV-positive smokers were assigned to the intervention group and received ( a ) 21 mg nicotine patch therapy for 6 weeks , ( b ) weekly face-to-face or telephone counseling , and ( c ) skills training that included substitute strategies for dealing with not smoking . Those participants assigned to the control group received written self-help material s for smoking cessation . Abstinence rates at end of intervention and 8 months were compared between groups . At end of treatment , 62.5 % of intervention group participants were biochemically confirmed as abstinent from smoking compared with 0 % in the control group . Eight-month abstinence rates were 50 % among the intervention group compared with 0 % in the control group Abstract Tobacco dependence is prevalent among alcohol dependent patients , and causes increased morbidity and mortality . Concurrent treatment for these disorders may be advantageous , but there are concerns about adverse effects on alcohol treatment outcomes . The Timing of Alcohol and Smoking Cessation ( TASC ) Study is a r and omized controlled clinical trial to compare the effectiveness of smoking cessationtreatment offered concurrently or six months following intensive rehabilitation for alcohol dependence . This paper describes the study design and baseline characteristics of the study population . Participants were current smokers in intensive alcohol dependence treatment , with willingness to consider quitting smoking . Smoking intervention offered behavioral and pharmacological treatment . One thous and nine hundred forty — three patients were screened for enrollment ; 499 were eligible and participated ( 26 % ) . We describe demographic characteristics , smoking behavior and attitudes among participants and non participants toward smoking cessation and drinking . We conclude that there is considerable interest in smoking cessation in alcohol dependent treatment population s , and recruitment to research studies is feasible BACKGROUND People with severe mental ill health are three times more likely to smoke but typically do not access conventional smoking cessation services , contributing to widening health inequalities and reduced life expectancy . We aim ed to pilot an intervention targeted at smokers with severe mental ill health and to test methods of recruitment , r and omisation , and follow up before implementing a full trial . METHODS The Smoking Cessation Intervention for Severe Mental Ill Health Trial ( SCIMITAR ) is a pilot r and omised controlled trial of a smoking cessation strategy design ed specifically for people with severe mental ill health , to be delivered by mental health nurses and consisting of behavioural support and drugs , compared with a conventional smoking cessation service ( ie , usual care ) . Adults ( aged 18 years or older ) with bipolar disorder or schizophrenia , who were current smokers , were recruited from NHS primary care and mental health setting s in the UK ( York , Scarborough , Hull , and Manchester ) . Eligible participants were r and omly allocated to either usual care ( control group ) or usual care plus the bespoke smoking cessation strategy ( intervention group ) . R and omisation was done via a central telephone system , with computer-generated r and om numbers . We could not mask participants , family doctors , and research ers to the treatment allocation . Our primary outcome was smoking status at 12 months , verified by carbon monoxide measurements or self-report . Only participants who provided an exhaled CO measurement or self-reported their smoking status at 12 months were included in the primary analysis . The trial is registered at IS RCT N.com , number IS RCT N79497236 . FINDINGS Of 97 people recruited to the pilot study , 51 were r and omly allocated to the control group and 46 were assigned to the intervention group . Participants engaged well with the bespoke smoking cessation strategy , but no individuals assigned to usual care accessed NHS smoking cessation services . At 12 months , 35 ( 69 % ) controls and 33 ( 72 % ) people assigned to the intervention group provided a CO measurement or self-reported their smoking status . Smoking cessation was highest among individuals who received the bespoke intervention ( 12/33 [ 36 % ] vs 8/35 [ 23 % ] ; adjusted odds ratio 2·9 , 95 % CI 0·8 - 10·5 ) . INTERPRETATION We have shown the feasibility of recruiting and r and omising people with severe mental ill health in a trial of this nature . The level of engagement with a bespoke smoking cessation strategy was higher than with a conventional approach . The effectiveness and safety of a smoking cessation programme design ed particularly for people with severe mental ill health should be tested in a fully powered r and omised controlled trial . FUNDING National Institute of Health Research Health Technology Assessment Programme AIM To evaluate potential mediators of an extended cognitive behavioral smoking cessation intervention . DESIGN Analysis of data from a r and omized clinical trial of smoking cessation . SETTING The Habit Abatement Clinic , University of California , San Francisco . PARTICIPANTS Participants were older cigarette smokers ( > /=50 years old ) . Those receiving St and ard Treatment ( N=100 ) were compared to those receiving extended cognitive behavioral treatment ( N=99 ) . MEASUREMENTS Negative affect was measured with the Profile of Mood States ( POMS ) , the Medical Outcome Studies 36-item Short-Form Health Survey ( SF-36 ) , and the Perceived Stress Scale ( PSS ) . Abstinence-specific social support was measured with the Partner Interaction Question naire ( PIQ ) . Motivation to quit and abstinence self-efficacy were measured on 1 - 10 scales with the Thoughts about Abstinence Question naire . All were measured at the beginning of treatment and week 52 . RESULTS Analyses revealed that extended CBT increased abstinence self-efficacy over the first 52 weeks postcessation . This effect , in turn , was positively associated with 7-day point prevalence abstinence at week 64 while controlling for treatment condition , and eliminated the independent effect of treatment condition on abstinence . The test of mediation indicated a significant effect , and abstinence self-efficacy accounted for 61 % to 83 % of the total effect of treatment condition on smoking abstinence . Results failed to support a mediational role of negative affect , abstinence-specific social support , or motivation to quit . CONCLUSIONS The results of the present study are consistent with theories of relapse and studies of more time-limited interventions , and underscore the importance of abstinence self-efficacy in achieving long-term abstinence from cigarettes BACKGROUND Action aim ed at changing smoking behavior to prevent cardiovascular patients from further impairing their health is advisable . Cognitive behavioral interventions can be effective in this regard since they attempt to influence cognitive determinants that presumably lead to smoking cessation . The Minimal Intervention Strategy for Cardiology patients ( C-MIS ) is such an intervention , tailored to the patients ' readiness to change . Our aim is to investigate whether the C-MIS is successful in changing patients ' cognitions such as attitudes , social influence , self-efficacy and intention to quit during a 1-year period . METHODS Smoking out patients ( N = 315 ) with cardiovascular disease were included . They were r and omized and received either Nicotine Replacement Therapy ( NRT ) or NRT + C-MIS . At baseline ( T1 ) , sociodemographic and clinical characteristics were measured . Cognitions and quitting behavior were assessed at baseline and at four follow-up measurements . RESULTS Comparing treatments , the C-MIS did not affect pros of quitting , pros of smoking and social influence . We did find small effects of the C-MIS on intention to quit and self-efficacy , although only for higher-educated patients . CONCLUSION The C-MIS appears successful in affecting intention to quit and self-efficacy abilities , but only for patients with higher education levels . Initial positive changes in cognitions may also emerge in a medical intervention , such as the provision of NRT Despite high smoking rates among those living in poverty , few cessation studies are conducted in these population s. This cluster-r and omized trial tested nicotine gum plus motivational interviewing ( MI ) for smoking cessation in 20 low-income housing developments ( HDs ) . Intervention participants ( 10 HDs , n = 66 ) received educational material s , 8 weeks of 4 mg nicotine gum , and 5 MI sessions on quitting smoking . Comparison participants ( 10 HDs , n = 107 ) received 5 MI sessions and educational material s addressing fruit and vegetable consumption . Participants had a mean age of 46.3 years and were predominantly female ( 70 % ) and African American ( 83 % ) . Biochemically-verified 7-day abstinence rates at 8 weeks were 6.1 % and 5.6 % in the intervention and comparison arms , respectively ( p = ns ) ; and at 26 weeks were 7.6 % and 9.3 % , respectively ( p = ns ) . Results suggest that nicotine gum plus MI were not effective for smoking cessation in low-income housing . Programs are needed to enhance the effectiveness of pharmacotherapy and counseling in underserved population BACKGROUND Lack of interest has been cited as a reason not to offer cessation assistance to smokers , but research suggests that smokers accept treatments offered proactively . This study assessed acceptability , utilization , and effectiveness of free smoking cessation treatment among diverse primary care patients . METHOD Medical assistants invited 4174 adult smokers to participate . Enrollees ( 1869 ) self-selected or were assigned to receive free nicotine patch therapy alone or in combination with the Committed Quitters(R ) program , and for some , individual counseling . RESULTS In nearly 68 % of cases , patients accepted a treatment invitation ; 77 % of eligible smokers enrolled ; 85 % of these picked up free patches . Given a choice of treatments , 75 % of participants elected a psychosocial treatment in addition to patch therapy . Thirteen percent of treatment initiators achieved biochemically confirmed 7-day point-prevalence abstinence at 1 year , with no significant treatment effects . Minority patients showed greater initial interest but less utilization did than White patients . CONCLUSIONS Free , readily accessible smoking cessation treatment offered in primary care setting s was accepted and used by the majority of unselected smokers of diverse racial/ethnic origins . Psychosocial treatment components did not significantly increase abstinence rates . Barriers , rather than lack of interest , may keep minority smokers from using cessation treatments OBJECTIVES The objective was to determine the efficacy of an emergency department (ED)-based smoking cessation intervention . METHODS This study was a r and omized trial conducted from January 2006 to September 2007 at an urban ED that treats 90,000 adults per year . Discharged adults who smoked at least 10 cigarettes per day were r and omized to 1 ) usual care , receiving a smoking cessation brochure ; or 2 ) enhanced care , receiving the brochure , a motivational interview ( MI ) , nicotine patches , and a phone call at 3 days . Interventions were performed by a peer educator trained in tobacco treatment . Blinded follow-up was performed at 3 months . RESULTS A total of 338 subjects were enrolled , mean ( ±SD ) age was 40.2 ( ±12.0 ) years , 51.8 % were female , and 56.5 % were either self-pay or Medicaid . Demographic and clinical variables were comparable between groups . Enhanced and usual care arms showed similar cessation rates at 3 months ( 14.7 % vs. 13.2 % , respectively ) . The proportion of subjects making a quit attempt ( 69.2 % vs. 66.5 % ) and decrease in daily cigarette use ( five vs. one ; all p > 0.05 ) were also similar . In logistic modeling , factors associated with quitting included any tobacco-related International Classification of Diseases , ninth revision ( ICD-9 ) , code for the ED visit ( odds ratio [OR]= 3.42 , 95 % confidence interval [ CI ] = 1.61 to 7.26 ) or subject belief that the ED visit was tobacco-related ( OR = 2.47 , 95 % CI = 1.17 to 5.21 ) . Conversely , subjects who reported having a preexisting tobacco-related illness were less likely to quit ( OR = 0.22 , 95 % CI = 0.10 to 0.50 ) . CONCLUSIONS The primary endpoint was negative , reflecting a higher-than-expected quit rate in the control group . Subjects whose ED visit was tobacco-related , based either on physician diagnosis or subject perception , were more than twice as likely to quit . These data suggest that even low-intensity screening and referral may prompt substantial numbers of ED smokers to quit or attempt to quit BACKGROUND Cigarette smoking is the greatest cause of preventable mortality in the United States . Because most smokers would like to quit and most hospitals are smoke free , surgical admissions represent a window of opportunity for tobacco cessation interventions . METHODS A total of 324 patients ( 98 % men ) , aged 25 to 82 years , who were current smokers and who underwent noncardiac surgery were enrolled in a r and omized controlled trial at the Veterans Affairs Medical Center , San Francisco , Calif. One hundred sixty-eight participants ( 52 % ) received a multicomponent intervention design ed to increase self-efficacy and coping skills that included face-to-face in-hospital counseling , viewing a smoking cessation videotape , self-help literature , nicotine replacement therapy , and 3 months of telephone follow-up . One hundred fifty-six participants ( 48 % ) received self-help literature and brief counseling lasting 10 minutes . Serum or saliva cotinine levels were measured to confirm self-reported smoking cessation . RESULTS At 12 months of follow-up , the self-reported quit rate was 27 % among the intervention group and 13 % among the comparison group ( relative risk , 2.1 ; 95 % confidence interval , 1.2 - 3.5 ; P < .01 ) . Based on biochemical confirmation , 15 % of the intervention group , compared with 8 % of the comparison group , quit smoking at 12 months ( relative risk , 2.0 ; 95 % confidence interval , 1.0 - 3.9 ; P = .04 ) . CONCLUSIONS A smoking cessation intervention targeted at smokers hospitalized for noncardiac surgery can increase long-term quit rates . Surgical hospitalizations provide an opportunity to reach smokers who want to quit smoking BACKGROUND There is a high prevalence of smoking among people who experience severe mental ill health ( SMI ) . Helping people with disorders such as bipolar illness and schizophrenia to quit smoking would help improve their health , increase longevity and also reduce health inequalities . Around half of people with SMI who smoke express an interest in cutting down or quitting smoking . There is limited evidence that smoking cessation can be achieved for people with SMI . Those with SMI rarely access routine NHS smoking cessation services . This suggests the need to develop and evaluate a behavioural support and medication package tailored to the needs of people with SMI . OBJECTIVE The objective in this project was to conduct a pilot trial to establish acceptability of the intervention and to ensure the feasibility of recruitment , r and omisation and follow-up . We also sought preliminary estimates of effect size in order to design a fully powered trial of clinical effectiveness and cost-effectiveness . The pilot should inform a fully powered trial to compare the clinical effectiveness and cost-effectiveness of a bespoke smoking cessation ( BSC ) intervention with usual general practitioner ( GP ) care for people with SMI . DESIGN A pilot pragmatic two-arm individually r and omised controlled trial ( RCT ) . Simple r and omisation was used following a computer-generated r and om number sequence . Participants and practitioners were not blinded to allocation . SETTING Primary care and secondary care mental health services in Engl and . PARTICIPANTS Smokers aged > 18 years with a severe mental illness who would like to cut down or quit smoking . INTERVENTIONS A BSC intervention delivered by mental health specialists trained to deliver evidence -supported smoking cessation interventions compared with usual GP care . MAIN OUTCOME MEASURES The primary outcome was carbon monoxide-verified smoking cessation at 12 months . Smoking-related secondary outcomes were reduction of number of cigarettes smoked , Fagerstrom test of nicotine dependence and motivation to quit ( MTQ ) . Other secondary outcomes were Patient Health Question naire-9 items and Short Form Question naire-12 items to assess whether there were improvements or deterioration in mental health and quality of life . We also measured body mass index to assess whether or not smoking cessation was associated with weight gain . These were measured at 1 , 6 and 12 months post r and omisation . RESULTS The trial recruited 97 people aged 19 - 73 years who smoked between 5 and 60 cigarettes per day ( mean 25 cigarettes ) . Participants were recruited from four mental health trusts and 45 GP surgeries . Forty-six people were r and omised to the BSC intervention and 51 people were r and omised to usual GP care . The odds of quitting at 12 months was higher in the BSC intervention ( 36 % vs. 23 % ) but did not reach statistical significance ( odds ratio 2.9 ; 95 % confidence interval 0.8 % to 10.5 % ) . At 3 and 6 months there was no evidence of difference in self-reported smoking cessation . There was a non-significant reduction in the number of cigarettes smoked and nicotine dependence . MTQ and number of quit attempts all increased in the BSC group compared with usual care . There was no difference in terms of quality of life at any time point , but there was evidence of an increase in depression scores at 12 months for the BSC group . There were no serious adverse events thought likely to be related to the trial interventions . The pilot economic analysis demonstrated that it was feasible to carry out a full economic analysis . CONCLUSIONS It was possible to recruit people with SMI from primary and secondary care to a trial of a smoking cessation intervention based around behavioural support and medication . The overall direction of effect was a positive trend in relation to biochemically verified smoking cessation and it was feasible to obtain follow-up in a substantial proportion of participants . A definitive trial of a bespoke cessation intervention has been prioritised by the National Institute for Health Research ( NIHR ) and the SCIMITAR pilot trial forms a template for a fully powered RCT to examine clinical effectiveness and cost-effectiveness . TRIAL REGISTRATION Current Controlled Trials IS RCT N79497236 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment , Vol . 19 , No. 25 . See the NIHR Journals Library website for further project information AIMS To test the efficacy of two smoking cessation interventions in a HIV positive ( HIV+ ) sample : st and ard care ( SC ) treatment plus nicotine replacement therapy ( NRT ) versus more intensive motivationally enhanced ( ME ) treatment plus NRT . DESIGN R and omized controlled trial . SETTING HIV+ smoker referrals from eight immunology clinics in the northeastern United States . PARTICIPANTS A total of 444 participants enrolled in the study ( mean age = 42.07 years ; 63.28 % male ; 51.80 % European American ; mean cigarettes/day = 18.27 ) . INTERVENTIONS SC participants received two brief sessions with a health educator . Those setting a quit date received self-help quitting material s and NRT . ME participants received four sessions of motivational counseling and a quit-day counseling call . All ME intervention material s were tailored to the needs of HIV+ individuals . MEASUREMENTS Biochemically verified 7-day abstinence rates at 2-month , 4-month and 6-month follow-ups . FINDINGS Intent-to-treat ( ITT ) abstinence rates at 2-month , 4-month and 6-month follow-ups were 12 % , 9 % and 9 % , respectively , in the ME condition , and 13 % , 10 % and 10 % , respectively , in the SC condition , indicating no between-group differences . Among 412 participants with treatment utilization data , 6-month ITT abstinence rates were associated positively with low nicotine dependence ( P = 0.02 ) , high motivation to quit ( P = 0.04 ) and Hispanic American race/ethnicity ( P = 0.02 ) . Adjusting for these variables , each additional NRT contact improved the odds of smoking abstinence by a third ( odds ratio = 1.32 , 95 % confidence interval = 0.99 - 1.75 ) . CONCLUSIONS Motivationally enhanced treatment plus NRT did not improve cessation rates over and above st and ard care treatment plus NRT in this HIV+ sample of smokers . Providers offering brief support and encouraging use of nicotine replacement may be able to help HIV+ patients to quit smoking INTRODUCTION Phone counseling has become st and ard for behavioral smoking cessation treatment . Newer options include Web and integrated phone-Web treatment . No prior research , to our knowledge , has systematic ally compared the effectiveness of these three treatment modalities in a r and omized trial . Underst and ing how utilization varies by mode , the impact of utilization on outcomes , and predictors of utilization across each mode could lead to improved treatments . METHODS One thous and two hundred and two participants were r and omized to phone , Web , or combined phone-Web cessation treatment . Services varied by modality and were tracked using automated systems . All participants received 12 weeks of varenicline , printed guides , an orientation call , and access to a phone supportline . Self-report data were collected at baseline and 6-month follow-up . RESULTS Overall , participants utilized phone services more often than the Web-based services . Among treatment groups with Web access , a significant proportion logged in only once ( 37 % phone-Web , 41 % Web ) , and those in the phone-Web group logged in less often than those in the Web group ( mean = 2.4 vs. 3.7 , p = .0001 ) . Use of the phone also was correlated with increased use of the Web . In multivariate analyses , greater use of the phone- or Web-based services was associated with higher cessation rates . Finally , older age and the belief that certain treatments could improve success were consistent predictors of greater utilization across groups . Other predictors varied by treatment group . CONCLUSIONS Opportunities for enhancing treatment utilization exist , particularly for Web-based programs . Increasing utilization more broadly could result in better overall treatment effectiveness for all intervention modalities INTRODUCTION Although homeless individuals smoke at an alarmingly high rate , few smoking cessation clinical trials have focused on this vulnerable population . Little is known about recruitment efforts and suitable eligibility criteria for tobacco control research in homeless population s. METHODS The aim of this article is to describe the recruitment , eligibility , and enrollment of homeless smokers who participated in the Power to Quit smoking study , a r and omized smoking cessation clinical trial funded by the National Institutes of Health . The study compared motivational interviewing and st and ard counseling while participants received an 8-week treatment of the nicotine patch . RESULTS Working with local emergency shelters , a total of 839 adult smokers were screened for study eligibility , 580 of whom ( 69.1 % ) met eligibility criteria . Of those eligible , 430 ( 74.1 % ) returned for r and omization . Those who returned for r and omization were older and more likely to have a phone number compared with eligible participants not enrolled . The most common reasons for exclusion included exhaled carbon monoxide levels less than or equal to 5 parts per million ( indicating nonsmoking status ) , use of smoking cessation aid during the past 30 days , and not meeting the study definition of homelessness . CONCLUSION Knowledge of these factors may help research ers tailor criteria that accurately identify and include homeless smokers in future research OBJECTIVE To examine whether reimbursement for Provider Counseling , Pharmacotherapies , and a telephone Quitline increase smoking cessation relative to Usual Care . STUDY DESIGN R and omized comparison trial testing the effectiveness of four smoking cessation benefits . SETTING Seven states that best represented the national population in terms of the proportion of those > or = 65 years of age and smoking rate . PARTICIPANTS There were 7,354 seniors voluntarily enrolled in the Medicare Stop Smoking Program and they were followed-up for 12 months . INTERVENTION(S ) ( 1 ) Usual Care , ( 2 ) reimbursement for Provider Counseling , ( 3 ) reimbursement for Provider Counseling with Pharmacotherapy , and ( 4 ) telephone counseling Quitline with nicotine patch . MAIN OUTCOME MEASURE Seven-day self-reported cessation at 6- and 12-month follow-ups . PRINCIPAL FINDINGS Unadjusted quit rates assuming missing data = smoking were 10.2 percent ( 9.0 - 11.5 ) , 14.1 percent ( 11.7 - 16.5 ) , 15.8 percent ( 14.4 - 17.2 ) , and 19.3 percent ( 17.4 - 21.2 ) at 12 months for the Usual Care , Provider Counseling , Provider Counseling + Pharmacotherapy , and Quitline arms , respectively . Results were robust to sociodemographics , smoking history , motivation , health status , and survey nonresponse . The additional cost per quitter ( relative to Usual Care ) ranged from several hundred dollars to $ 6,450 . CONCLUSIONS A telephone Quitline in conjunction with low-cost Pharmacotherapy was the most effective means of reducing smoking in the elderly AIMS To assess the effects of adding motivational interviewing ( MI ) counseling to nicotine patch for smoking cessation among homeless smokers . DESIGN Two-group r and omized controlled trial with 26-week follow-up . PARTICIPANTS AND SETTING A total of 430 homeless smokers from emergency shelters and transitional housing units in Minneapolis/St Paul , Minnesota , USA . INTERVENTION AND MEASUREMENTS All participants received 8-week treatment of 21-mg nicotine patch . In addition , participants in the intervention group received six individual sessions of MI counseling which aim ed to increase adherence to nicotine patches and to motivate cessation . Participants in the st and ard care control group received one session of brief advice to quit smoking . Primary outcome was 7-day abstinence from cigarette smoking at 26 weeks , as vali date d by exhaled carbon monoxide and salivary cotinine . FINDINGS Using intention-to-treat analysis , verified 7-day abstinence rate at week 26 for the intervention group was non-significantly higher than for the control group ( 9.3 % versus 5.6 % , P = 0.15 ) . Among participants who did not quit smoking , reduction in number of cigarettes from baseline to week 26 was equally high in both study groups ( -13.7 ± 11.9 for MI versus -13.5 ± 16.2 for st and ard care ) . CONCLUSIONS Adding motivational interviewing counseling to nicotine patch did not increase smoking rate significantly at 26-week follow-up for homeless smokers PURPOSE Partnership for Health ( PFH ) was found to increase smoking cessation among smokers in the Childhood Cancer Survivors Study ( CCSS ) at the 8- and 12-month postbaseline follow-up . This report provides outcomes at 2 to 6 years postbaseline ; the primary outcome is a four-category smoking status variable ( quit at all follow-ups , quit at final follow-up only , smoker at all follow-ups , and smoker at final follow-up only ) ; quit attempts among those who reported smoking at the final follow-up is a secondary outcome . METHODS PFH was a r and omized control trial with two conditions , peer phone counseling ( PC ) and self-help ( SH ) , that involved smokers ( n = 796 ) enrolled in the CCSS cohort . RESULTS Long-term quit rates were higher in PC versus SH participants . Long-term smoking cessation outcomes were lower among those who were nicotine dependent , of lower educational levels , and among men , and were higher among those who used nicotine replacement therapy and who had higher levels of situational self-efficacy . There were no significant differences in relapse rates between conditions or in quit attempts among continued smokers . CONCLUSION Cessation rates continue to be significantly higher among participants in the PC condition versus SH , although the differences were not large . This article highlights differences in long-term engagement with smoking cessation among those who received the intervention OBJECTIVES We evaluated the efficacy of a motivational tobacco cessation treatment combined with nicotine replacement relative to usual care initiated in inpatient psychiatry . METHODS We r and omized participants ( n = 224 ; 79 % recruitment rate ) recruited from a locked acute psychiatry unit with a 100 % smoking ban to intervention or usual care . Prior to hospitalization , participants averaged 19 ( SD = 12 ) cigarettes per day ; only 16 % intended to quit smoking in the next 30 days . Results . Verified smoking 7-day point prevalence abstinence was significantly higher for intervention than usual care at month 3 ( 13.9 % vs 3.2 % ) , 6 ( 14.4 % vs 6.5 % ) , 12 ( 19.4 % vs 10.9 % ) , and 18 ( 20.0 % vs 7.7 % ; odds ratio [ OR ] = 3.15 ; 95 % confidence interval [ CI ] = 1.22 , 8.14 ; P = .018 ; retention > 80 % ) . Psychiatric measures did not predict abstinence ; measures of motivation and tobacco dependence did . The usual care group had a significantly greater likelihood than the intervention group of psychiatric rehospitalization ( adjusted OR = 1.92 ; 95 % CI = 1.06 , 3.49 ) . CONCLUSIONS The findings support initiation of motivationally tailored tobacco cessation treatment during acute psychiatric hospitalization . Psychiatric severity did not moderate treatment efficacy , and cessation treatment appeared to decrease rehospitalization risk , perhaps by providing broader therapeutic benefit Background : Predictors of smoking cessation ( SC ) treatment outcome were explored in a multisite clinical trial of SC treatment at community-based , outpatient , substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network . Objectives : To explore baseline demographic and clinical predictors of abstinence during treatment . Methods : Cigarette smokers from five methadone maintenance programs and two drug and alcohol dependence treatment programs were r and omly assigned to SC treatment as an adjunct to substance abuse treatment as usual or to substance abuse treatment as usual . SC treatment consisted of group counseling ( weeks 1–8 ) plus transdermal nicotine patch treatment ( 21 mg/day , weeks 1–6 ; 14 mg/day , weeks 7–8 ) . Demographic and clinical predictors of smoking abstinence were evaluated among those patients assigned to the active SC condition ( N = 153 ) using logistic regression . Results : Abstinence during treatment was positively associated with younger age , Hispanic or Caucasian ( as opposed to African American ) ethnicity/race , employment or student status , fewer cigarettes per day at baseline , lower severity of the primary substance problem at baseline , and higher methadone doses ( among the sub sample in methadone treatment ) . Conclusions and Scientific Significance : During future efforts to improve SC treatments among drug- and alcohol-dependent patients , consideration should be given to adequate treatment to reduce the severity of the primary drug or alcohol problem , tailoring treatments for patients with greater severity of smoking and of the primary substance problem , and culturally sensitive interventions . Analysis of predictors of outcome may be a useful tool for treatment development Cigarette smoking is highly prevalent among people living with HIV/AIDS and poses unique health risks . Smoking cessation programs tailored to this population have documented improved smoking outcomes with nicotine replacement therapy ( NRT ) . The current study examined 6-month abstinence rates from a r and omized clinical trial targeting 412 HIV-positive adult current smokers ( 51 % European American , 19 % African American , and 17 % Hispanic American ) and tested whether psychosocial variables , such as self-efficacy and decisional balance , mediated the relationship between NRT and long-term abstinence . Meeting criteria for complete mediation , 6-month smoking abstinence rates improved significantly with increases in these mediators , and the association of NRT and smoking abstinence was no longer significant once changes in self-efficacy and decisional balance were taken into account . Failure to translate gains in self-efficacy among African Americans into improved abstinence rates accounted for racial/ethnic differences among participants . Specific psychosocial factors , such as self-efficacy , may be particularly amenable to change in cessation interventions and should be addressed with greater awareness of how cultural and social context ual factors impact treatment response among people living with HIV/AIDS The purpose of this study was to investigate expectancies regarding the interaction between cigarette smoking and use of alcohol among alcohol-dependent smokers in early recovery , using the Nicotine and Other Substances Interaction Expectancies Question naire ( NOSIE ) . Participants were 162 veterans , 97 % male , with a mean age of 50 years , enrolled in a clinical trial aim ed at determining the efficacy of an intensive smoking cessation intervention versus usual care . At baseline , participants were assessed on measures of smoking behavior , abstinence thoughts about alcohol and tobacco use , symptoms of depression , and smoking-substance use interaction expectancies . In addition , biologically verified abstinence from tobacco and alcohol was assessed at 26 weeks . Participants reported that they expected smoking to have less of an impact on substance use than substance use has on smoking ( p < .001 ) . Severity of depressive symptoms was significantly associated with the expectancy that smoking provides a way of coping with the urge to use other substances ( p < .01 ) . The expectation that smoking increases substance urges/use was predictive of prospect ively measured and biologically verified abstinence from smoking at 26 weeks ( p < .03 ) . The results add to our knowledge of smoking-substance use interaction expectancies among alcohol-dependent smokers in early recovery and will inform the development of more effective counseling interventions for concurrent alcohol and tobacco use disorders |
2,393 | 26,318,178 | The nonsurgical group had significantly greater wrist flexion , radial deviation , and ulnar variance and less radial inclination than the surgical group .
Conclusions Surgical and nonsurgical methods produce similar results in the treatment of DRFS in the elderly , and minor objective functional differences did not result an impact on subjective function outcome and quality of life | Purpose The best treatment of distal radius fractures ( DRFs ) in the elderly is uncertain .
The purpose of this meta- analysis was to compare the outcomes of surgical and nonsurgical management of DRFs in persons 65 years of age or older . | PURPOSE To compare complication rates for distal radius fractures treated operatively versus nonsurgical in patients older than 65 years . We hypothesized that surgical intervention would improve fracture alignment , but it would be associated with more complications and equivalent functional outcomes when compared with the nonsurgical group . METHODS Patients ( operative , n = 129 ) and controls ( nonsurgical , n = 129 ) were identified from a prospect i ve clinical and operating room data base . They were matched on fracture severity ( AO-A/B/C1 vs AO-C2/C3 ) , sex , age , and energy of injury . Data on complications were extracted from medical charts using a vali date d complications checklist , and radiologic data were collected for all patients . Functional outcomes ( Patient-Related Wrist Evaluation ) at 1 year were available in only a subset of patients . We determined differences in complication and reoperation rates using a chi-square test . RESULTS A significant number of patients experienced complications in the operative group ( operative = 37 of 129 ; nonsurgical = 22 of 129 ) . The most common complication was median neuropathy ( n = 8 operative ; n = 14 nonsurgical ) , followed by surgical site infections ( n = 16 operative ; 12 of 16 were pin site infections ) and complex regional pain syndrome ( n = 4 operative ; 3 nonsurgical ) . The complication rate in patients treated with volar plate was 22 % ( 16 of 74 ) , for dorsal plate it was 50 % ( 2 of 4 ) , for external fixation it was 42 % ( 16 of 38 ) , and for percutaneous pinning it was 23 % ( 3 of 13 ) . The number of patients requiring reoperations was similar in both groups ( 11 [ 9 % ] operative ; 7 [ 5 % ] nonsurgical ) . Our secondary radiologic and functional outcomes demonstrate that despite a higher incidence of malunion in nonsurgical patients ( nonsurgical : 69 % vs operative : 29 % ) , a subset of patients from both groups ( n = 140 ) had minimal pain and disability at 1 year ( Patient-Related Wrist Evaluation operative : 16.9 ± 23.2 ; nonsurgical : 15.7 ± 17.5 ) . CONCLUSIONS In a study matching fracture severity , sex , age , and energy of injury , we found that elderly patients with distal radius fractures who underwent surgery had higher complication rates than those treated nonsurgically . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic III We carried out a prospect i ve r and omised controlled clinical trial to compare the functional and radiological outcomes of casting with percutaneous pinning in treating extra-articular distal radial fracture in an elderly Chinese population . Sixty patients were r and omly allocated by sealed envelopes to either a ‘ Cast ’ group ( n = 30 ) or a ‘ K-wire ’ group ( n = 30 ) . All patients were available for final follow-up assessment . The radiological outcomes in terms of dorsal angulation , radial inclination and radial length were statistically significantly better in the K-wire group , whereas the Mayo wrist score and quality of life , healing rate , healing time , and complications were similar . The functional outcomes and quality of life were not affected by the treatments . Both treatments had a very low rate of complication and high healing rates PURPOSE The aim of this study was to compare the functional and radiographic outcomes of dorsally displaced distal radius fractures treated by closed reduction plaster cast fixation ( CRPCF ) and external fixation ( EF ) in patients 65 years and older . METHODS This retrospective and nonr and omized study comprised 46 consecutive patients older than 65 years who had distal radial fractures . Patients were divided into 2 groups according to treatment : a CRPCF group and an EF group . All the fractures were dorsally displaced and AO/ASIF type A or C , without articular stepoff or gap . Cases were evaluated based on the criteria of Disabilities of the Arm , Shoulder , and H and ( DASH ) question naire score , wrist range of motion , and radiologic results . RESULTS The mean follow-up period was 25.1 months . Union was achieved in all cases . Although it was not a statistically significant difference , posttreatment complications were more common in the CRPCF group ( 10 patients ) than in the EF group ( 7 patients ) . In the CRPCF group , most complications were discomfort from the cast , whereas in the EF group , most were pin site infections . The average wrist extension and ulnar deviation ( clinical ly ) and palmar tilt and radial height ( radiologically ) were statistically better in the EF group at the final follow-up . The mean DASH scores were 20.3 in the CRPCF group and 21.9 in the EF group . There was no statistically significant difference in the DASH scores ; in wrist flexion , radial deviation , pronation , supination , grip strength , or pinch strength ( clinical ly ) ; or in ulnar variance or radial inclination ( radiologically ) . There was no correlation between the DASH scores and palmar tilt and ulnar variance . CONCLUSIONS We concluded that both CRPCF and EF are useful methods for distal radius fractures in elderly patients . The results showed significant differences in wrist extension and ulnar deviation BACKGROUND Despite the recent trend toward the internal fixation of distal radial fractures in older patients , the currently available literature lacks adequate r and omized trials examining whether open reduction and internal fixation ( ORIF ) with a volar locking plate is superior to nonoperative ( cast ) treatment . The purpose of the present r and omized clinical trial was to compare the outcomes of two methods that were used for the treatment of displaced and unstable distal radial fractures in patients sixty-five years of age or older : ( 1 ) ORIF with use of a volar locking plate and ( 2 ) closed reduction and plaster immobilization ( casting ) . METHODS A prospect i ve r and omized study was performed . Seventy-three patients with a displaced and unstable distal radial fracture were r and omized to ORIF with a volar locking plate ( n = 36 ) or closed reduction and cast immobilization ( n = 37 ) . The outcome was measured on the basis of the Patient-Rated Wrist Evaluation ( PRWE ) score ; the Disabilities of the Arm , Shoulder and H and ( DASH ) score ; the pain level ; the range of wrist motion ; the rate of complications ; and radiographic measurements including dorsal radial tilt , radial inclination , and ulnar variance . RESULTS There were no significant differences between the groups in terms of the range of motion or the level of pain during the entire follow-up period ( p > 0.05 ) . Patients in the operative treatment group had lower DASH and PRWE scores , indicating better wrist function , in the early postoperative time period ( p < 0.05 ) , but there were no significant differences between the groups at six and twelve months . Grip strength was significantly better at all times in the operative treatment group ( p < 0.05 ) . Dorsal radial tilt , radial inclination , and radial shortening were significantly better in the operative treatment group than in the nonoperative treatment group at the time of the latest follow-up ( p < 0.05 ) . The number of complications was significantly higher in the operative treatment group ( thirteen compared with five , p < 0.05 ) . CONCLUSIONS At the twelve-month follow-up examination , the range of motion , the level of pain , and the PRWE and DASH scores were not different between the operative and nonoperative treatment groups . Patients in the operative treatment group had better grip strength through the entire time period . Achieving anatomical reconstruction did not convey any improvement in terms of the range of motion or the ability to perform daily living activities in our cohorts OBJECTIVE To compare the differences of the efficacy between the conservative treatment and surgical treatment for unstable distal radius fractures with surgical indications . METHODS From March 2008 to July 2011 , the patients with unstable distal radius fractures were devided into the surgical treatment group and the conservative treatment group in a non r and omized manner . In the surgical group , there were 16 males and 32 females with an average age of 50.26 years old ranging from 22 to 76 years ; in the conservative treatment group there were 10 males and 27 females with an average age of 51.12 years old ranging from 42 to 79 years . The patients of two groups were almost all with falling damage trauma , which accounting for 92.94 % ( 79/85 ) , all the patients were closed injury , 41 cases were in the left side , and 44 cases in the right . Fracture in accordance with AO classification : C1 in 12 cases , C2 in 32 cases , C3 in 38 cases , B3 in 3 cases . Patients in the surgical treatment group were treated with volar locking compression plate ( LCP ) fixation and patients in the conservative were treated with manual reduction and plaster external fixation . The active wrist range of motion , pain assessment , subjective evaluation , Gartl and and Werley score , Batra radiology score and complications were observed in the last follow-up . RESULTS Forty-three patients in the surgical treatment group were followed up for an average time of 8.03 months ( 4 to 15 months ) ; 33 paitents in the conservative group were followed up for an average time of 6.54 months ( 2 to 9 months ) . The difference of the wrist joint active dorsiflexion and supination rotation range in the two groups were statistically significant ( t = 2.212 , P < 0.05 ; t = 2.392 , P < 0.05 ) ; the difference of the proportion of patients with ulnar wrist pain in the two groups was statistically significant ( chi2 = 5.71 , P < 0.05 ) ; the difference of patients ' subjective evaluation score of two groups was statistically significant ( Z = 2.13 , P < 0.05 ) ; the difference of Gartl and and Werley score between the two groups was statistically significant ( Z = 2.36 , P < 0.05 ) ; the difference of Batra radiology score in the two groups was statistically significant ( Z = 2.58 , P < 0.05 ) ; the differences in the X-ray measurement of the proportion of distal radial shortening > or = 5 mm , the radial height ( shortening ) was statistically significant ( for the correction chi2 = 7.57 , P < 0.05 ; t = 2.016 , P < 0.05 ) ; the differences of malunion rate , ulnar impaction syndrome , the incidence rate of ulnar styloid fracture nonunion of two groups was statistically significant ( adjusted chi2 = 10.05 , P < 0.05 ; chi2 = 8.39 , P < 0.05 ; chi2 = 5.51 , P < 0.05 ) . CONCLUSION For patients with surgical indications for unstable distal radius fractures , every indicator of the outcome after surgery in the treatment is better than that of the manipulative reduction and plaster fixation BACKGROUND From 2000 to 2012 , the annual incidence of inpatient treatment for distal radius fracture in Germany rose from 65 to 86 per 100 000 persons . It is unclear whether open reduction and volar angle-stable plate osteo synthesis ( ORIF ) , a currently advocated treatment , yields a better functional outcome or quality of life than closed reposition and casting . METHODS In the ORCHID multi-center trial , 185 patients aged 65 and older with an AO type C distal radial fracture were r and omly assigned to ORIF or closed reposition and casting . Their health-related quality of life and h and /arm function were assessed 3 and 12 months afterward with the Short Form 36 ( SF-36 ) question naire and the Disability of the Arm , Shoulder and H and ( DASH ) question naire . The radiological findings , range of movement of the wrist , and EuroQol-5D ( EQ-5D ) scores were documented as well . RESULTS Among the 149 patients in the intention-to-treat- analysis , there was no significant difference in SF-36 scores between the two treatment groups at one year ( mean difference , 3.3 points in favor of ORIF ; 95 % confidence interval , -0.2 + 6.8 points ; p = 0.058 ) . The DASH scores showed moderately strong , but clinical ly unimportant effects in favor of ORIF , and there was no difference in EQ-5D scores . ORIF led to better radiological results and wrist mobility at 3 months , with comparable results at 12 months . 37 of the patients initially allotted to nonsurgical treatment underwent secondary surgery due to significant loss of reduction . CONCLUSION The findings with respect to mobility , functionality , and quality of life at 12 months provide marginal and inconsistent evidence for the superiority of volar angle-stable plate osteo synthesis over closed reduction and casting in the treatment of intra-articular distal radius fractures . Primary nonsurgical management is also effective in suitable patients OBJECTIVE To examine the incidence and predictors of complex regional pain syndrome type I ( CRPS I ) after fracture of the distal radius . DESIGN Prospect i ve study . SETTING University hospital . PARTICIPANTS A consecutive sample of patients ( N=90 ) with fracture of the distal radius treated by closed reduction and casting . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Occurrence of CRPS I , occurrence of pain , wrist and h and range of motion , radiographic measures , Patient-Rated Wrist Evaluation , Hospital Anxiety and Depression Scale , and Medical Outcomes Study 36-Item Short-Form Health Survey at baseline and 1 , 3 , 6 , and 9 months follow-up . RESULTS CRPS I occurred in 29 patients ( 32.2 % ) with a mean delay ± SD of 21.7±23.7 days from cast removal . Univariate analyses found significant differences between patients with CRPS I and patients without CRPS I at baseline for sex ( P=.021 ) , socioeconomic level ( P=.023 ) , type of trauma ( P=.05 ) , pain at rest and activity ( P=.006 and P<.001 , respectively ) , wrist dorsiflexion and pronation ( P=.002 and P=.001 , respectively ) , finger flexion ( P=.047 ) , thumb opposition ( P=.002 ) , function of the h and ( P<.001 ) , and physical quality of life ( QOL ) ( P=.013 ) . Logistic regression showed that risk for CRPS I was higher in cases of women ( odds ratio [OR]=5.774 ; 95 % confidence interval [ CI ] , 1.391 - 23.966 ) , medium and low energy trauma patients ( OR=7.718 ; 95 % CI , 1.136 - 52.44 ) , patients with a Medical Outcomes Study 36-Item Short-Form Health Survey physical functioning score < 40 ( OR=4.931 ; 95 % CI , 1.428 - 17.025 ) , and patients with Patient-Rated Wrist Evaluation pain subscale score > 16 ( OR=12.192 ; 95 % CI , 4.484 - 43.478 ) . CONCLUSIONS CRPS I occurs frequently during the third and fourth week after cast removal , especially in women who report severe pain and impairment of physical QOL . Additional prospect i ve studies are required to verify these findings in comminuted and operated fractures of the distal radius Objectives : To compare final functional and radiographic outcomes of closed reduction and casting ( CAST ) with open reduction and internal fixation ( ORIF ) with palmar locking plate for unstable Colles type distal radius fractures ( DRFs ) in low-dem and patients older than 70 years . Design : Retrospective , clinical study . Setting : Level 1 university trauma center . Patients : Over a mean period of 4 years and 7 months , 130 consecutive patients older than 70 years were treated for an unstable dorsally displaced DRF of which 114 or 87 % were followed for 1 year or longer . Intervention : ORIF ( n = 53 ) using volar locking plate or closed reduction and casting ( n = 61 ) . Main Outcome Measurements : Objective and subjective functional results ( active range of motion ; grip strength ; disabilities of the arm , shoulder and h and ( DASH ) score ; patient-rated wrist evaluation ( PRWE ) score ; visual analog scale ; and Green and O'Brien score ) and radiographic assessment ( dorsal tilt , radial inclination , radial shortening , fracture union , and posttraumatic arthritis ) were assessed . Results : At final follow-up , there was no significant difference between the 2 groups for mean ranges of motion , grip strength , DASH score , PRWE score , and Green and O'Brien score . Pain level was significantly less for the patients in the CAST group . An obvious clinical deformity was present in 77 % of cast group and none in the ORIF group . At final follow-up , in the ORIF group , there was a mean loss of dorsal tilt of 1.3 degrees , radial inclination of 0.3 degrees , and radial length of 0.5 mm compared with the postoperative measurements . No primary acceptable reduction was achieved in 44 % of the CAST group . At final follow-up , in the CAST group , dorsal tilt , radial inclination , and radial shortening averaged −24.4 ± 12 degrees , 19.2 ± 6.5 degrees , and + 3.9 ± 2.7 mm , respectively . Malunion occurred in 89 % primarily reduced fractures . Dorsal tilt , radial inclination , and radial shortening were significantly better in the ORIF group . Conclusions : Radiographic results ( dorsal tilt , radial inclination , and radial shortening ) after unstable dorsally displaced DRFs are significantly better in patients treated by ORIF using a volar fixed-angle plate rather than those treated by cast immobilization ( P < 0.05 ) . At a mean follow-up time of 4 years and 7 months , the clinical outcomes of active range of motion , the PRWE , DASH , and Green and O'Brien scores do not differ between the 2 methods of treatment . The pain level was significantly less in the CAST group ( P < 0.05 ) , and this group experienced no complications . There was no difference between the subjective and functional outcomes for the surgical and the nonsurgical treatments in a cohort of patients older than 70 years . Unsatisfactory radiographic outcome in older patients does not necessarily translate into unsatisfactory functional outcome . Nonoperative treatment may be the preferred method of treatment in this age group BACKGROUND Vitamin C has been proposed to improve outcomes after a distal radial fracture by promotion of bone and soft-tissue healing and reduction of the prevalence of complex regional pain syndrome ( CRPS ) . Our primary aim was to examine the effect of vitamin C on functional outcome after a distal radial fracture . METHODS A total of 336 adult patients with an acute fracture of the distal aspect of the radius were recruited over a one-year period and r and omized to receive 500 mg of vitamin C or placebo daily for fifty days after the fracture . The primary outcomes were the DASH ( Disabilities of the Arm , Shoulder and H and ) score at six weeks and at one year . Secondary variables included complications , wrist and finger motion , grip and pinch strength , pain , and a CRPS score . RESULTS There were no significant differences in patient or fracture characteristics between the treatment groups . There was no significant effect of vitamin C on the DASH score throughout the study period . At six weeks , patients in the vitamin C group with a nondisplaced fracture had a significantly greater wrist flexion deficit ( p = 0.008 ) and pinch strength deficit ( p = 0.020 ) and a greater rate of CRPS ( p = 0.022 ) , but there was no difference in the CRPS rate at any other time point . At twenty-six weeks , there was a higher rate of complications ( p = 0.043 ) and greater pain with use ( p = 0.045 ) in the patients with a displaced fracture treated with vitamin C. There was no significant difference in the time to fracture-healing . CONCLUSIONS This study demonstrated no significant difference at one year in the DASH score , other functional outcomes , the rate of CRPS , or osseous healing of nondisplaced or displaced distal radial fractures treated with vitamin C compared with placebo . We conclude that administration of vitamin C confers no benefit to patients with a displaced or nondisplaced fracture of the distal aspect of the radius . LEVEL OF EVIDENCE Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence UNLABELLED The objective of this study was comparing the results of the conservative ( close reduction and immobilisation in the plaster splint ) vs operative ( percutaneous Kirschner-wiring ) treatment of fractures of the distal radius . Sixty patients , 49 women ( 82 % ) and 11 men ( 18 % ) , who sustained an isolated , displaced fractures were r and omly allocated to operative ( 30 patients ) or conservative ( 30 patients ) treatment . All patients were followed up at 1.5 , 3 and finally at 6 months after fracture . The following variables were analysed : rate of secondary displacement , wrist range of motion , fingers loss of flexion , total grip strength , dorsal or volar tilt , radial angulation and radial length on the X-ray . Function of the h and was assessed with DASH question naire , cold sensitivity with McCabe scale and final outcome in Gartl and -Werley and Castaing complex scales . The rate of secondary displacement was considered a primary outcome measure . RESULTS Secondary displacement was noted in 8 patients ( 27 % ) treated conservatively , of whom 7 required surgery and those were withdrawn from the trial . Three fractures ( 10 % ) treated operatively displaced secondarily , but none required additional operation and all completed the follow-up . The rate of secondary displacement was statistically significantly ( chi2 test , p < 0.05 ) more frequent in conservatively treated group . With regard to other analysed parameters , the statistically significant differences was found in total grip strength at 3 and 6 months assessment s , and in DASH score at 6 months assessment , both favouring operative method . The remaining variables did not differ significantly between the groups treated conservatively and operatively . CONCLUSION Our results have demonstrated , that percutaneous Kirschner-wiring of fractures of the distal radius is superior to the conservative treatment , because statistically significantly reduces the risk of secondary displacement and allows to obtain a stronger grip and better h and function within 6 months after fracture INTRODUCTION Intra-articular fractures of the distal radius represent high energy , complex , unstable injuries and the optimal method of treatment remains controversial . MATERIAL S AND METHODS The aim of the paper is to compare the outcomes of external fixation ( EF ) with open reduction internal fixation ( ORIF ) with plates and screw fixation in the treatment of intra-articular fractures of the distal radius . Thirty-five patients were enlisted from December 2003 to September 2005 after a failure of initial conservative treatment . The patients were r and omised into EF or ORIF groups . The patients were followed-up at 1 week , 3 , 6 , 12 and 24 months . Clinical and radiological outcomes were measured . They were scored using the Green and O'Brien or the Gartl and and Wertley score . RESULTS Of the 35 patients , 5 defaulted the 6-month follow-up and were excluded . We found that the clinical and radiological outcomes for the 2 groups were not significantly different . Complication rates were also similar . CONCLUSION There is no significant difference in the outcome of intra-articular distal radius fractures treated with either EF or ORIF |
2,394 | 30,466,413 | While use of technology in hearing conservation educational programs offers promise , its effectiveness has not been studied | Background Many youth and young adults experience high noise exposure compounded by lack of access to hearing health education .
Although the need for hearing health education programs is evident , the efficacy of these programs for youth is unclear .
We evaluated the literature for efficacy of various hearing conservation programs aim ed at youth and young adults , and analyzed their strengths and limitations . | OBJECTIVES ( 1 ) To conduct a contemporary analysis of historical data on short-term efficacy of a 3-year hearing conservation program conducted from 1992 to 1996 in Wisconsin , USA , with 753 high school students actively involved in farm work ; ( 2 ) to establish procedures for assessment of hearing loss for use in a recently funded follow-up of this same hearing conservation program cohort . METHODS We analyzed a pragmatic cluster-r and omized controlled trial , with schools as the unit of r and omization . Thirty-four rural schools were recruited and r and omized to intervention or control . The intervention included classroom instruction , distribution of hearing protection devices , direct mailings , noise level assessment s , and yearly audiometric testing . The control group received the audiometric testing . RESULTS Students exposed to the hearing conservation program reported more frequent use of hearing protection devices , but there was no evidence of reduced levels of noise-induced hearing loss ( NIHL ) . CONCLUSION Our analysis suggests that , since NIHL is cumulative , a 3-year study was likely not long enough to evaluate the efficacy of this intervention . While improvements in reported use of hearing protection devices were noted , the lasting impact of these behaviors is unknown and the finding merits corroboration by longer term objective hearing tests . A follow-up study of the cohort has recently been started OBJECTIVES : Concerts have long periods of intense sound with short break intervals . Hearing concerns are well known to performers ; concertgoers largely ignore them . Preperformance and postperformance audiograms were compared to assess hearing threshold shifts with and without earplugs . METHODS : A prospect i ve , r and omized study in which 29 volunteers attended 3 concerts , encompassing 3 music genres . Audiograms , seating location , sound intensity , and earplug-use data were collected . Data were analyzed to determine frequency test-retest variability . RESULTS : Sound levels averaged 99.8 dBA , and the maximum was 125.6 dBA . Sixty-four percent ( 9/14 ) of participants without earplugs showed significant threshold shifts compared with 27 % ( 4/15 ) of those using earplugs . No significant differences existed between music genres or seating location . CONCLUSIONS : This study showed a high incidence of threshold shifts in unprotected concertgoers . Sound levels exceeded all Occupational Safety and Health Act rules despite st and ardized sound systems . A significant reduction in threshold shifts was seen with the use of earplugs This experiment investigated the effect of small-group versus individual hearing loss prevention ( HLP ) training on the attenuation performance of passive insert-type hearing protection devices ( HPDs ) . A subject-fit ( SF ) methodology , which gave naive listeners access only to the instructions printed on the HPD product label , was used to determine real-ear attenuation at threshold ( REAT ) at third-octave noise b and s between 125–8000 Hz . REAT measurements were augmented by use of the Hearing Loss Prevention Attitude-Belief ( HLPAB ) survey , a field-tested self- assessment tool developed by the National Institute for Occupational Safety and Health ( NIOSH ) . Participants were r and omly assigned to one of four experimental groups , consisting of 25 listeners each , in a controlled behavioral-intervention trial . There were two types of HPDs ( formable and premolded ) and two training formats ( individual and small group ) . A short multimedia program , including a practice session , was presented to all 100 listeners . Results showed training to have a significant effect , for both HPDs on real-ear attenuation and attitude , but , importantly , there was no difference between small-group and individual training Background About 15 % of adolescents in the Netherl and s have mental health problems and many also have health risk behaviours such as excessive alcohol consumption , cigarette smoking , use of drugs , and having unsafe sex . Mental health problems and health risk behaviours may have adverse effects on the short and longer term . Therefore , in the Netherl and s there is a considerable support for an additional public health examination at age 15–16 years . The study evaluates the effect of two options for such an additional examination . Adolescents in the ‘ E-health4Uth ’ group receive internet-based tailored health messages on their health behaviour and well-being . Adolescents in the ‘ E-health4Uth + counselling ’ group receive the computer-tailored messages combined with personal counselling for adolescents at risk of mental health problems . Methods and design A three-arm cluster r and omised controlled trial will be conducted in the Netherl and s among fourth- grade secondary school students . School classes are the unit of r and omisation . Both intervention groups complete the computer-tailored program during one class session ; the program focuses on nine topics related on health behaviour and well-being . For each topic a score is computed that can be compared with the Dutch health norms for adolescents . Based on the score , a message is presented that reflects the person ’s current behaviour or well-being , the Dutch health norm , and offers advise to change unhealthy behaviour or to talk to a person they trust . Adolescents in the ‘ E-health4Uth + counselling ’ group are also invited for an appointment to see the nurse when they are at risk of mental health problems . The control group receives ‘ care as usual’.The primary outcome measures are health behaviour ( alcohol , drugs , smoking , safe sex ) and mental health status . The secondary outcome measure is health-related quality of life . Data will be collected with a question naire at baseline and at 4-months follow-up . A process evaluation will also be conducted . Discussion It is hypothesized that at follow-up adolescents in the ‘ E-health4Uth ’ group and adolescents in the ‘ E-health4Uth + counselling ’ group will show fewer mental health problems and less risky behaviour compared to the control group . Trial registration Current Controlled Trials OBJECTIVE To assess the impact of a web-based intervention supplemented with text messages to reduce cancer risk linked with smoking , unhealthy diet , alcohol consumption , obesity , sedentary lifestyle and sun exposure . METHODS A total of 2001 voluntary adolescents from Spain and Mexico were recruited between 2009 and 2012 and r and omly assigned to : one control group and two experimental groups , which received exclusively the online intervention ( experimental group 1 ) or the intervention supplemented with encouraging text messages ( experimental group 2 ) . The educational intervention was based on both : successful psychosocial models ( i.e. A.S.E. and Transtheoretical model ) and the school curriculum . RESULTS After a 9-month follow-up , the prevalence of students who did not eat fruit was reduced significantly in all groups : experimental group 1 ( -62.6 % ) , experimental group 2 ( -71.5 % ) and even the control group ( -66.8 % ) . Being overweight was only reduced in the experimental group 2 ( -19.6 % ) . The total cancer behavioral risk score , which ranged from 0 to 100 points ( highest risk ) , was significantly reduced in the experimental group 1 ( -3.5 points ) and in the experimental group 2 ( -5.3 points ) . The text-supplemented online intervention increased the probability of improving the post-test total cancer behavioral risk ( OR=1.62 ) . CONCLUSION The web-based intervention supplemented with text messages had a positive global impact , but it lead to only minimal changes in risky behaviors . This intervention appears useful in controlling overweight adolescents . CLINICAL TRIAL REGISTRATION NUMBER IS RCT N27988779 OBJECTIVE To assess the efficacy of a hearing conservation program in changing acoustic risk-taking and hearing conservation behaviors in elementary school children . STUDY DESIGN Prospect i ve , r and omized , mixed design controlled study . METHODS Participants were grade -six students from 16 Vancouver School Board schools . Differences between the intervention and control group responses on a behavioral question naire were measured at baseline , and then at 2 weeks and 6 months after administration of a hearing conservation program ( Sound Sense ™ ) . RESULTS The intervention result ed in significant interactions for improved earplug use at dances ( P = .019 ) , rock concerts ( P = .001 ) , with percussion musical instruments ( P = .002 ) , and electric guitars ( P = .028 ) at 2 weeks postintervention relative to baseline . Improvements in children 's earplug use at dances ( P = .041 ) , rock concerts ( P = .0024 ) , and with power lawn mowers ( P = .043 ) at 6 months postintervention relative to baseline were also observed . Behavior in the intervention group compared to control group improved in earplug use with any " other noises " at 2 weeks ( P = .001 ) , and 6 months ( P = .022 ) relative to baseline . There was a tendency in the intervention group to reduce the duration of use of personal music devices at 2 weeks and 6 months after the hearing conservation program , which was nonsignificant . CONCLUSION The Sound Sense ™ hearing conservation program improved earplug use practice s in elementary school children in the short and long term . The development , implementation and evaluation of a community-based health promotion project around hearing loss can serve as a tremendous opportunity for students to develop their knowledge and skills in health advocacy Adolescents working in agricultural setting s may be exposed to noise levels that result in hearing loss . The article describes the design , implementation , and results of a four-year , hearing conservation program ( HCP ) conducted at school . Thirty-four schools ( 753 students ) were r and omly assigned to either an intervention or control group . The intervention included multicomponent educational strategies and employed features of an industrial HCP . Final compliance surveys indicated 87.5 % of intervention students reported using hearing protection devices ( HPD ) at least some of the time , compared to 45 % of control students . The HCP components with the greatest reported influence were distribution of HPDs for use on the farm and yearly hearing tests . Eighty percent of intervention students reported intention to use HPDs in the future . It is feasible to conduct a hearing conservation program with junior high school and senior high school students , and it appears possible to persuade teen-agers to protect themselves from exposure to loud noise while working on a farm Abstract Objective : Adolescent farmworkers are exposed to loud noise during farm activities . We present a prospect i ve study that evaluated the efficacy of low-cost , technology-based intervention approaches in high schools to enhance the use of hearing protection among adolescent farmworkers . Design : Six high schools in Iowa that agreed to participate in the study were divided into three equal groups through cluster-r and omisation with each group receiving one of the three formats of hearing protection intervention : ( a ) classroom training , ( b ) classroom training coupled with smartphone app training and ( c ) computer training . Participants completed baseline ( pre-training ) and six-week post-intervention surveys for assessing hearing protection knowledge , attitudes and behaviour . Study Sample : Seventy participants from six schools were initially enrolled but 50 completed both pre- and post-intervention surveys . Results : In most cases , all three groups showed significant improvement in hearing protection knowledge , attitude and frequency of use from pre- to post-intervention . However , changes between groups were statistically non-significant . Conclusions : Although all three formats led to improvements on hearing protection knowledge , attitude and behaviour , the findings of the study , perhaps due to the small sample size , did not allow us to detect whether technology-based hearing protection interventions were more effective than the traditional face-to-face training for adolescent farmworkers OBJECTIVES : We had the rare opportunity to conduct a cluster-r and omized controlled trial to observe the long-term ( 16-year ) effects of a well- design ed hearing conservation intervention for rural high school students . This trial assessed whether the intervention result ed in ( 1 ) reduced prevalence of noise-induced hearing loss ( NIHL ) assessed clinical ly and /or ( 2 ) sustained use of hearing protection devices . METHODS : In 1992–1996 , 34 rural Wisconsin schools were recruited and 17 were assigned r and omly to receive a comprehensive , 3-year , hearing conservation intervention . In 2009–2010 , extensive efforts were made to find and contact all students who completed the original trial . Participants in the 16-year follow-up study completed an exposure history question naire and a clinical audiometric examination . Rates of NIHL and use of hearing protection were compared . RESULTS : We recruited 392 participants from the original trial , 200 ( 53 % ) from the intervention group and 192 ( 51 % ) from the control group . Among participants with exposure to agricultural noise , the intervention group reported significantly greater use of hearing protection compared with the control group ( 25.9 % vs 19.6 % ; P = .015 ) . The intervention group also reported significantly greater use of hearing protection for shooting guns ( 56.2 % vs 41.6 % ; P = .029 ) , but the groups reported similar uses of protection in other context s. There was no significant difference between groups with respect to objective measures of NIHL . CONCLUSION : This novel trial provides objective evidence that a comprehensive educational intervention by itself may be of limited effectiveness in preventing NIHL in a young rural population PURPOSE Few computer-based HIV , sexually transmitted infection ( STI ) , and pregnancy prevention programs are available , and even fewer target early adolescents . In this study , we tested the efficacy of It 's Your Game (IYG)-Tech , a completely computer-based , middle school sexual health education program . The primary hypothesis was that students who received IYG-Tech would significantly delay sexual initiation by ninth grade . METHODS We evaluated IYG-Tech using a r and omized , two-arm nested design among 19 schools in a large , urban school district in southeast Texas ( 20 schools were originally r and omized ) . The target population was English-speaking eighth- grade students who were followed into the ninth grade . The final analytic sample included 1,374 students . Multilevel logistic regression models were used to test for differences in sexual initiation between intervention and control students , while adjusting for age , gender , ethnicity , time between measures , and family structure . RESULTS There was no significant difference in the delay of sexual activity or in any other sexual behavior between intervention and control students . However , there were significant positive between-group differences for psychosocial variables related to STI and condom knowledge , attitudes about abstinence , condom use self-efficacy , and perceived norms about sex . Post hoc analyses conducted among intervention students revealed some significant associations : " full exposure " ( completion of all 13 lessons ) and " mid-exposure " ( 5 - 8 lessons ) students were less likely than " low exposure " ( 1 - 4 lessons ) students to initiate sex . CONCLUSIONS Collectively , our findings indicate that IYG-Tech impacts some determinants of sexual behavior , and that additional efficacy evaluation with full intervention exposure may be warranted OBJECTIVES We conducted a comprehensive evaluation of a rural youth health and safety initiative implemented in 4000 National FFA ( formerly Future Farmers of America ) chapters across the United States . METHODS Data were collected from high school students and their FFA advisers at 3 time intervals ( preintervention , immediate postintervention , and 1 year postintervention ) with a 3-group ( st and ard , enhanced , and control ) , cluster-r and omized , controlled trial design . RESULTS Matched data from 3081 students and 81 advisers revealed no significant effect of this initiative on agricultural health and safety knowledge , safety attitudes , leadership , self-concept , and self-reported injuries of project participants . Data from 30 public health nurses following the intervention confirmed the program 's failure to develop sustainable community partnerships . CONCLUSIONS This nationally coordinated initiative was funded with more than $ 1 million donated by agribusinesses . Program implementation was inconsistent , and desired outcomes were not achieved . Future efforts should better guide effective use of private sector re sources aim ed at reducing agricultural disease and injury among rural youths Abstract Objective : To evaluate the effectiveness of four NIHL prevention interventions at improving knowledge , attitudes , and intended behaviors regarding sound exposure and appropriate use of hearing protective strategies in children . Design : A r and omized trial of the four interventions with a non-intervention comparison group . Question naires were completed prior to , immediately after , and three months after each intervention . Study : Interventions included : ( 1 ) A classroom presentation by older-peer educators , ( 2 ) A classroom presentation by health professionals , ( 3 ) . Exploration of a museum exhibition , and ( 4 ) . Exploration of an internet-based virtual museum . A comparison group received no intervention . Study sample : Fifty-three fourth grade classrooms ( 1120 students ) participated in the study . Results : All interventions produced significant improvements but the number of improvements decreased over time . In terms of effectiveness , the classroom programs were more effective than the internet-based virtual exhibit , which was more effective than the visit to the museum exhibition . Self-reported exposures indicated that as many as 94.5 % of participants were at risk for NIHL . Conclusions : Interpersonal , interactive educational interventions such as the classroom program are more effective and have longer impact than self-directed learning experiences for NIHL and tinnitus prevention , however each may have an important role in promoting hearing health in elementary school students BACKGROUND Adolescents with asthma are at risk of poor outcomes and are traditionally difficult to reach . OBJECTIVE To examine adolescents ' use of and asthma outcomes associated with smartphone- vs paper-based asthma action plans ( AAPs ) . METHODS We conducted a 6-month r and omized clinical trial with adolescents ( 12 - 17 years old ) with persistent asthma . Participants used their respective smartphone or paper AAPs for medication instructions and peak flow or asthma symptoms logging . AAP use was measured electronically for smartphone users and via mail-in diaries for the paper group . Changes in Asthma Control Test ( ACT ) and self-efficacy scores were examined . RESULTS Thirty-four adolescents participated in this study ( median age , 15.4 years ) . Participants were mostly African American ( 62 % ) with state-issued insurance ( 71 % ) . Adolescents in the smartphone group accessed the AAP a median of 12.17 times per week or 4.36 days per week but only recorded medications or symptoms and peak flow data in the electronic diary a median of 10 days per month during the 6-month period . Participants in the paper group recorded data a median of 23.5 days per month on their paper diaries . Overall , there were no changes in ACT and self-efficacy scores between groups . Adolescents with uncontrolled asthma ( baseline ACT score ≤19 ) had an improvement in ACT for the smartphone group ( before , 11 ; after , 20 ) ( [ P = .04 ) compared with no change in the paper group ( before , 17 ; after , 17 ) ( P = .64 ) . Adolescent satisfaction with the application was high , with 100 % stating they would recommend the smartphone AAP to a friend . CONCLUSION Adolescents were frequent and highly satisfied users of the smartphone AAP with a subset of participants with uncontrolled asthma demonstrating possible clinical benefit . Findings suggest a need for larger-scale studies to determine the effectiveness of smartphone-based AAPs among high-risk patients with asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT02091869 BACKGROUND AND OBJECTIVE The Physiotherapy Evidence Data base ( PEDro ) scale has been widely used to investigate method ological quality in physiotherapy r and omized controlled trials ; however , its validity has not been tested for pharmaceutical trials . The aim of this study was to investigate the validity and interrater reliability of the PEDro scale for pharmaceutical trials . The reliability was also examined for the Cochrane Back and Neck ( CBN ) Group risk of bias tool . METHODS This is a secondary analysis of data from a previous study . We considered r and omized placebo controlled trials evaluating any pain medication for chronic spinal pain or osteoarthritis . Convergent validity was evaluated by correlating the PEDro score with the summary score of the CBN risk of bias tool . The construct validity was tested using a linear regression analysis to determine the degree to which the total PEDro score is associated with treatment effect sizes , journal impact factor , and the summary score for the CBN risk of bias tool . The interrater reliability was estimated using the Prevalence and Bias Adjusted Kappa coefficient and 95 % confidence interval ( CI ) for the PEDro scale and CBN risk of bias tool . RESULTS Fifty-three trials were included , with 91 treatment effect sizes included in the analyses . The correlation between PEDro scale and CBN risk of bias tool was 0.83 ( 95 % CI 0.76 - 0.88 ) after adjusting for reliability , indicating strong convergence . The PEDro score was inversely associated with effect sizes , significantly associated with the summary score for the CBN risk of bias tool , and not associated with the journal impact factor . The interrater reliability for each item of the PEDro scale and CBN risk of bias tool was at least substantial for most items ( > 0.60 ) . The intraclass correlation coefficient for the PEDro score was 0.80 ( 95 % CI 0.68 - 0.88 ) , and for the CBN , risk of bias tool was 0.81 ( 95 % CI 0.69 - 0.88 ) . CONCLUSION There was evidence for the convergent and construct validity for the PEDro scale when used to evaluate method ological quality of pharmacological trials . Both risk of bias tools have acceptably high interrater reliability STUDY OBJECTIVE To examine a computer-assisted , counselor-guided motivational intervention ( CAMI ) aim ed at reducing the risk of unprotected sexual intercourse . DESIGN , SETTING , PARTICIPANTS , INTERVENTIONS , AND MAIN OUTCOME MEASURES : We conducted a 9-month , longitudinal r and omized controlled trial with a multisite recruitment strategy including clinic , university , and social referrals , and compared the CAMI with didactic educational counseling in 572 female adolescents with a mean age of 17 years ( SD = 2.2 years ; range = 13 - 21 years ; 59 % African American ) who were at risk for pregnancy and sexually transmitted diseases . The primary outcome was the acceptability of the CAMI according to self-reported rating scales . The secondary outcome was the reduction of pregnancy and sexually transmitted disease risk using a 9-month , self-report timeline follow-back calendar of unprotected sex . RESULTS The CAMI was rated easy to use . Compared with the didactic educational counseling , there was a significant effect of the intervention which suggested that the CAMI helped reduce unprotected sex among participants who completed the study . However , because of the high attrition rate , the intent to treat analysis did not demonstrate a significant effect of the CAMI on reducing the rate of unprotected sex . CONCLUSION Among those who completed the intervention , the CAMI reduced unprotected sex among an at-risk , predominantly minority sample of female adolescents . Modification of the CAMI to address method ological issues that contributed to a high drop-out rate are needed to make the intervention more acceptable and feasible for use among sexually active predominantly minority , at-risk , female adolescents |
2,395 | 23,728,675 | Continuous monitoring of physiological variables for the first two to three days may improve outcomes and prevent complications . | BACKGROUND Explanations for the effectiveness of stroke units compared with general wards in reducing mortality , institutionalisation and dependence of people with stroke remain undetermined , and the discussion on the most effective stroke unit model is still up for debate .
The intensity of non-invasive mechanical monitoring in many western countries is one of the main issues regarding the different models .
This is because of its strong impact on the organisation of the stroke unit in terms of the number of personnel , their expertise , the infrastructure and costs .
OBJECTIVES To assess whether continuous intensive monitoring compared with intermittent monitoring of physiological variables in people with acute stroke can change their prognosis in terms of mortality or disability .
Attention to the changes in physiological variables is a key feature of a stroke unit , and can most likely be aided by continuous monitoring without complications related to immobility or to treatments triggered by the relief of abnormal physiological variables . | Background and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP BACKGROUND We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence -based management of fever , hyperglycaemia , and swallowing dysfunction in acute stroke units ( ASUs ) . METHODS In the Quality in Acute Stroke Care ( QASC ) study , a single-blind cluster r and omised controlled trial , we r and omised ASUs ( clusters ) in New South Wales , Australia , with immediate access to CT and on-site high dependency units , to intervention or control group . Patients were eligible if they spoke English , were aged 18 years or older , had had an ischaemic stroke or intracerebral haemorrhage , and presented within 48 h of onset of symptoms . Intervention ASUs received treatment protocol s to manage fever , hyperglycaemia , and swallowing dysfunction with multidisciplinary team building workshops to address implementation barriers . Control ASUs received only an abridged version of existing guidelines . We recruited pre-intervention and post-intervention patient cohorts to compare 90-day death or dependency ( modified Rankin scale [ mRS ] ≥2 ) , functional dependency ( Barthel index ) , and SF-36 physical and mental component summary scores . Research assistants , the statistician , and patients were masked to trial groups . All analyses were done by intention to treat . This trial is registered at the Australia New Zeal and Clinical Trial Registry ( ANZCTR ) , number ACTRN12608000563369 . FINDINGS 19 ASUs were r and omly assigned to intervention ( n=10 ) or control ( n=9 ) . Of 6564 assessed for eligibility , 1696 patients ' data were obtained ( 687 pre-intervention ; 1009 post-intervention ) . Results showed that , irrespective of stroke severity , intervention ASU patients were significantly less likely to be dead or dependent ( mRS ≥2 ) at 90 days than control ASU patients ( 236 [ 42 % ] of 558 patients in the intervention group vs 259 [ 58 % ] of 449 in the control group , p=0·002 ; number needed to treat 6·4 ; adjusted absolute difference 15·7 % [ 95 % CI 5·8 - 25·4 ] ) . They also had a better SF-36 mean physical component summary score ( 45·6 [ SD 10·2 ] in the intervention group vs 42·5 [ 10·5 ] in the control group , p=0·002 ; adjusted absolute difference 3·4 [ 95 % CI 1·2 - 5·5 ] ) but no improvement was recorded in mortality ( 21 [ 4 % ] of 558 in intervention group and 24 [ 5 % ] of 451 in the control group , p=0·36 ) , SF-36 mean mental component summary score ( 49·5 [ 10·9 ] in the intervention group vs 49·4 [ 10·6 ] in the control group , p=0·69 ) or functional dependency ( Barthel Index ≥60 : 487 [ 92 % ] of 532 patients vs 380 [ 90 % ] of 423 patients ; p=0·44 ) . INTERPRETATION Implementation of multidisciplinary supported evidence -based protocol s initiated by nurses for the management of fever , hyperglycaemia , and swallowing dysfunction delivers better patient outcomes after discharge from stroke units . Our findings show the possibility to augment stroke unit care . FUNDING National Health & Medical Research Council ID 353803 , St Vincent 's Clinic Foundation , the Curran Foundation , Australian Diabetes Society-Servier , the College of Nursing , and Australian Catholic University BACKGROUND AND PURPOSE The efficacy of stroke units has been extensively examined . It is unknown , however , whether the superiority of the stroke unit will remain after the increased focus on stroke treatment in general medicine . This study of patients admitted to the hospital early and with a short length of stay determines the effect and identifies certain important components of a stroke unit . METHODS Five hundred fifty patients aged 60 years or older with acute stroke were allocated by a quasi-r and omized design to a stroke unit or a general medical ward based on date of birth in the month . Patients admitted within 24 hours of onset were enrolled . Outcomes after 7 months were death , proportion needing long-term care , and change in neurological and functional state assessed by the Sc and inavian Stroke Scale and Barthel Index . RESULTS Seven months after admission there was a trend in favor of the stroke unit in all outcome measures , but no significant differences in clinical outcomes were found except for change in the Sc and inavian Stroke Scale score . Recurrent stroke during hospitalization occurred more often in the general medical ward ( P = .03 ) . The stroke unit was significantly more aggressive in mobilization out of bed ( P<.01 ) and use of parenteral fluid ( P<.0001 ) , aspirin ( P<.0001 ) , antipyretics ( P<.0001 ) , and antibiotics ( P<.0001 ) . CONCLUSIONS Our study confirms the benefit of the stroke unit , but the effects on the most reliable clinical outcomes were modest and insignificant . Treatment in this stroke unit hastened recovery . More aggressive rehabilitation and use of parenteral fluid , aspirin , antipyretics , and antibiotics appeared in the stroke unit Background : Stroke patients are more likely to make a good recovery if they receive care in a well-organised stroke unit . However , there are uncertainties about how best to provide such care . We studied 2 key aspects of early stroke unit care : early active mobilisation ( EM ) and automated monitoring ( AM ) for physiological complications such as hypoxia . Methods : This was an observer-blinded , factorial ( 2 × 2 ) pilot r and omised controlled trial recruiting stroke patients within 36 h of symptom onset . The patients were r and omised to 1 of 4 nurse-led treatment protocol s : ( a ) st and ard stroke unit care , ( b ) EM , ( c ) AM or ( d ) combined EM and AM . The primary outcome was the Rankin score at 3 months . We also report the data on feasibility and safety . Results : We r and omised 32 patients ( mean age = 65 years ; mean baseline modified NIH score = 6 ) . On unadjusted comparisons , the EM patients were significantly ( p < 0.05 ) more likely to mobilise very early ( within 1 h of r and omisation ) and to achieve walking by day 5 and were less likely to develop complications of immobility . The AM group was significantly ( p < 0.05 ) more likely to have pre-defined physiological complication events detected . All these associations remained , but were less statistically significant , after correcting for age , baseline NIH score and co- interventions . There were no significant safety concerns . Discussion : We have demonstrated the feasibility of implementing EM and AM for physiological complications in a r and omised controlled trial . Larger trials are warranted to determine whether these interventions have clinical benefits BACKGROUND In laboratory animals , cerebral ischaemia is worsened by hyperthermia and improved by hypothermia . Whether these observations apply to human beings with stroke is unknown . We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome . METHODS In a prospect i ve and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke ( median 2.4 h ) . We determined body temperature on admission , initial stroke severity , infa rct size , mortality , and outcome in survivors . Stroke severity was measured on admission , weekly , and at discharge on the Sc and inavian Stroke Scale ( SSS ) . Infa rct size was determined by computed tomography . Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age , gender , stroke severity on admission , body temperature , infections , leucocytosis , diabetes , hypertension , atrial fibrillation , ischaemic heart disease , smoking previous stroke , and comorbidity . FINDINGS Mortality was lower and outcome better in patients with mild hypothermia on admission ; both were worse in patients with hyperthermia . Body temperature was independently related to initial stroke severity ( p < 0.009 ) , infa rct size ( p < 0.0001 ) , mortality ( p < 0.02 ) , and outcome in survivors ( SSS at discharge ) ( p < 0.003 ) . For each 1 degrees C increase in body temperature the relative risk of poor outcome ( death or SSS score on discharge < 30 points ) rose by 2.2 ( 95 % CI 1.4 - 3.5 ) ( p < 0.002 ) . INTERPRETATION We have shown that , in acute human stroke , an association exists between body temperature and initial stroke severity , infa rct size , mortality , and outcome . Only intervention trials of hypothermic treatment can prove whether this relation is causal Background and Purpose — Although several studies have demonstrated the effectiveness of specialist Stroke Unit ( SU ) care of stroke patients , there is still disagreement over how these units are best organized . We sought to clarify the role of continuous monitoring of physiological parameters in acute ischemic stroke . Methods — We conducted a prospect i ve study of 268 first-ever ischemic stroke patients admitted to our Cerebrovascular Department and allocated , according to the availability of beds , to the SU or Cerebrovascular Unit ( CU ) . Statistical analysis compared mortality and outcome at discharge , medical and neurological complications , and length of hospitalization in the 2 care setting s. Results — Two hundred sixty-eight patients were enrolled . A good outcome at discharge , observed in 114 SU patients ( 85 % ) and 78 CU patients ( 58 % ) ( odds ratio , 2.63 ; 95 % CI , 1.4 to 4.8 ; P < 0.02 ) , was found , on multivariate analysis , to be significantly related to type of care ( SU versus CU ) . A significantly greater proportion of SU patients showed adverse changes in monitored parameters , which required acute medical treatment ( SU : 64 % ; CU : 19 % ; P < 0.0001 ) . The mean duration of these complications was significantly shorter in the SU patients ( SU : 1.0 day ; CU : 2.4 days ; P < 0.02 ) , and the outcome in patients experiencing complications covered by the monitoring protocol was significantly better in the SU ( 66 % ) than in the CU ( 35 % ) group ( P < 0.0001 ) . Conclusions — Admission of acute stroke patients to a monitoring SU may positively influence their outcome at discharge . Confirmation of our findings in larger trials will indicate the need for a revision of the minimum requirements of SUs , with the addition of monitoring as a new requirement BACKGROUND AND PURPOSE We have previously shown that treatment of acute stroke patients in our stroke unit ( SU ) compared with treatment in general ward ( GWs ) improves short- and long-term survival and functional outcome and increases the possibility of earlier discharge to home . The aim of the present study was to identify the differences in treatment between the SU and the GW and to assess which aspects of the SU care which were most responsible for the better outcome . METHODS Of the 220 patients included in our trial , only 206 were actually treated ( SU , 102 patients ; GW , 104 patients ) . For these patients , we identified the differences in the treatment and the consequences of the treatment . We analyzed the factors that we were able to measure and their association with the outcome , discharge to home within 6 weeks . RESULTS Characteristic features in our SU were teamwork , staff education , functional training , and integrated physiotherapy and nursing . Other treatment factors significantly different in the SU from the GW were shorter time to start of the systematic mobilization/training and increased use of oxygen , heparin , intravenous saline solutions , and antipyretics . Consequences of the treatment seem to be less variation in diastolic and systolic blood pressure ( BP ) , avoiding the lowest diastolic BP , and lowering the levels of glucose and temperature in the SU group compared with the GW group . Univariate analyses showed that all these factors except the level of glucose were significantly associated with discharge to home within 6 weeks . In the final multivariate Cox regression model , shorter time to start of the mobilization/training and stabilized diastolic BP were independent factors significantly associated with discharge to home within 6 weeks . CONCLUSIONS Shorter time to start of mobilization/training was the most important factor associated with discharge to home , followed by stabilized diastolic BP , indicating that these factors probably were important in the SU treatment . The effects of characteristic features of an SU , such as a specially trained staff , teamwork , and involvement of relatives , were not possible to measure . Such factors might be more important than those actually measured Background and Purpose — Pathophysiological considerations and observational studies indicate that elevated body temperature , hypoxia , hypotension , and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome . Methods — Both units were organized with the same st and ard care and multidisciplinary approach to nursing and rehabilitation . A blinded observer assessed functional outcome at 3 months with the modified Rankin scale ( mRS ) and Barthel Index ( BI ) . End points were ( 1 ) poor outcome , defined as either mRS ≥4 or BI < 60 or the need for institutional care and ( 2 ) mortality . Results — Fifty-four patients meeting the inclusion criteria were r and omized . The groups were well matched for baseline characteristics , stroke subtype , stroke severity , vascular risk factors , and prognostic factors . Poor outcome was seen in 7 ( 25.9 % ) patients in the SCMU group and in 13 ( 48.1 % ) in the SU group ( P = 0.16 ) . Mortality was lower in the SCMU group than in the SU group ( 1 [ 3.7 % ] vs 7 [ 25.9 % ] ; odds ratio , 0.11 [ 95 % CI , 0.02 to 0.96 ] , P = 0.05 ) . Conclusions — This pilot study suggests that admission of acute stroke patients to an SCMU may reduce mortality and poor outcome . A larger trial is required to confirm these findings Background and Purpose — The aims of the study were to examine the frequency and timing of predefined medical complications in unselected acute stroke patients treated in an acute comprehensive stroke unit and an early supported discharge service . Methods — Four hundred eighty-nine acute stroke patients were included and followed up with assessment s of 16 prespecified complications during the first week . Two hundred forty-four of the patients were r and omly allocated to a 3-month follow-up . Results — During the first week , 312 of 489 patients ( 63.8 % ) experienced 1 or more complications . The most common complications were pain in 117 patients ( 23.9 % ) , temperature ≥38 ° C in 116 ( 23.7 % ) , progressing stroke in 90 ( 18.4 % ) , urinary tract infection in 78 ( 16.0 % ) , troponin T elevation without criteria of myocardial infa rct ion in 57 ( 11.7 % ) , chest infections in 55 ( 11.2 % ) , nonserious falls in 36 ( 7.4 % ) , and myocardial infa rct ion in 22 ( 4.5 % ) , whereas stroke recurrence , seizure , deep venous thrombosis , pulmonary embolism , shoulder pain , serious falls , other infections , and pressure sores were each present in ≤2.5 % of patients . During the 3-month follow-up , 201 of 244 patients ( 82.4 % ) experienced at least 1 complication , the most common of which was pain , which occurred in 134 patients ( 53.3 % ) , followed by urinary tract infection in 68 ( 27.9 % ) and nonserious falls in 61 ( 25.0 % ) . The severity of stroke on admission was the most important risk factor for developing complications . Conclusions — This is the first study of complications in unselected acute stroke patients treated in a comprehensive stroke unit and early supported discharge service and shows that pain , progressing stroke , infections , myocardial infa rct ion , and falls are common complications , whereas others occur infrequently . Most complications occur during the first 4 days , and stroke severity is the most important risk factor Background and Purpose : Factors that determine the benefit of stroke units ( SU ) are unknown . The aim of our study was to analyze whether semi-intensive monitoring during the acute phase of stroke reduces mortality and dependency at long term . Methods : We studied patients with an ischemic stroke or intracerebral hemorrhage , consecutively admitted to our SU within 24 h of symptoms onset . Based on bed availability , patients were allocated to either a conventional care stroke unit ( C-SU , n = 209 ) or a semi-intensive stroke unit ( SI-SU , n = 321 ) with continuous monitoring of cardiac , respiratory , metabolic and neurological functions during the first 72 h. Both groups were treated following the same medical and nursing protocol s. Criteria for exclusion were patients with stupor/coma , previously dependent ( Barthel score < 85 ) and with TIA . Using logistic regression models , we analyzed the influence of semi-intensive care on mortality and dependency at one year . Results : Baseline characteristics were similar between patients admitted to the SI-SU and the C-SU , except for a higher frequency of more severe stroke and intracerebral hemorrhage in the SI-SU . Twenty-six percent of patients in the SI-SU and 4 % in the C-SU were r and omized in acute clinical trials ( p < 0.01 ) , and 61 % and 39 % were seen by a neurologist in less than 6 h from the onset of symptoms ( p < 0.01 ) . At 1 year , mortality and combined mortality and dependency were not significantly different between the two groups . However , due to the presence of a significant interaction between the type of unit and stroke severity , the OR of mortality for SI-SU allocation was 0.19 ( 95 % CI , 0.07–0.54 ) in patients with severe stroke ( CSS ≤4 ) , whereas it was 0.64 ( 95 % CI , 0.37–1.11 ) in those with mild-to-moderate stroke . Conclusions : This study suggests that semi-intensive monitoring in a stroke unit reduces mortality at 1 year in patients with severe stroke , with no influence over dependency |
2,396 | 19,210,499 | Based on the reliability of patch test data from the general population and exposure data obtained from patients with dermatitis , the prevalence and burden of fragrance sensitization in the general population is significant | BACKGROUND Contact sensitization to fragrance mix ( FM ) I and Myroxylon pereirae ( MP ) is common among European patients with dermatitis .
Recently , FM II was included in the European baseline series as an additional marker of fragrance sensitization .
OBJECTIVES This literature review aims to assess the prevalence of fragrance sensitization in the general population , and to suggest how future population -based studies and question naires should be constructed , better to assess the prevalence and burden of fragrance sensitization .
This is of relevance as it is often difficult to establish causality in biological systems . | The clinical implication s of sensitization to the fragrance material isoeugenol were studied in 19 subjects . Patch testing with serial dilutions of isoeugenol and a repeated open application test ( ROAT ) were performed The minimum effect level under patch test conditions was below 0.01 % isoeugenol in 4/19 ( 20 % ) of the test subjects . The ROAT was performed with a test solution of 0.2 % isoeugenol in ethanol . which is the recommended maximum concentration used in perfumes , ethanol being applied as vehicle control . 4 weeks was the maximum exposure period . The upper arm was used as test site the 1st 14 days and the upper arm as well as the neck for the next 14 days , 12/19 ( 63 % ) of test subjects had a positive ROAT . 4 of the responders ( 33 % ) reacted beyond day 7 , but none alter day 14 . Use testing on the neck for 14 days did not add any further ROAT‐positive cases , compared with testing on the upper arm . The sensitivity found on patch testing may be a guidance for the outcome of use tests with the same compound . In this study , all subjects with a positive use test to isoeugenol ( 0.2 % ) in ethanol also demonstrated on patch testing a minimum effect level of 0.2 % or lower . Data from serial dilution patch and use IC‐N may contribute significant information to assessment of the relationship between patch test responses and clinical contact hypersensitivity , and thus the safety of allergens used in cosmetics OBJECTIVES To assess the effect of incentive size on response rates , data quality , and cost in a digestive health status mail survey of a community sample of health plan enrollees . DATA SOURCES / SETTING The study population was selected from a data base of enrollees in various health plans obligated to receive care at Park Nicollet Clinic-HealthSystem Minnesota , a large , multispecialty group in Minneapolis , Minnesota , and the nearby suburbs . STUDY DESIGN A total of 1,800 HealthSystem Minnesota enrollees were r and omly assigned to receive a survey with an incentive of $ 5 or $ 2 . The response rates for each incentive level were determined . Data quality , as indicated by item nonresponse and scale scores , was measured . Total cost and cost per completed survey were calculated . PRINCIPAL FINDINGS The response rate among enrollees receiving $ 5 ( 74.3 percent ) was significantly higher than among those receiving $ 2 ( 67.4 percent ) ; differences were more pronounced in the first wave of data collection . Data quality did not differ between the two incentive groups . The total cost per completed survey was higher in the $ 5 condition than in the $ 2 condition . CONCLUSIONS A $ 5 incentive result ed in a higher response rate among a community patient sample with one mailing than did a $ 2 incentive . However , the response rates in the $ 2 condition approached the level of the $ 5 incentive , and costs were significantly lower when the full follow-up protocol was completed . Response rates were marginally increased by follow-up phone calls . The incentive level did not influence data quality . The results suggest if a survey budget is limited and a timeline is not critical , a $ 2 incentive provides an affordable means of increasing participation The pattern of patch test reactivity to nickel sulfate and fragrance mix was studied with respect to patch test performance , reproducibility and clinical relevance in a population of unselected infants followed prospect ively from birth to 18 months of age . TRUE Test ™ patches with nickel sulfate in 3 concentrations , 200 , 66 and 22 µg/cm2 , and fragrance mix 430 µg/cm2 were used . A likely case of nickel sensitivity was defined as a reproducible positive reaction with at least homogeneous erythema and palpable infiltration occurring at least 2 × and present at both the 12 and 18 months follow‐up . 543 infants ( 268 girls and 275 boys ) were tested at least 1 × , 304 were tested at both 12 and 18 months . The prevalence of a reproducible positive reaction to nickel was 8.6 % ( 20 girls and 6 boys ) . A transient positive reaction was observed in 111 children . Clinical relevance of nickel sensitivity was found in only 1 child . No reproducible positive reaction to fragrance mix was found . The high proportion of transient patch test reactivity to nickel sulfate 200 µg/cm2 indicates that this st and ard concentration used for adults can not be applied to infants . The interpretation of a single positive nickel patch test in infants must be assessed with caution and it is probably of non‐specific or irritant nature BACKGROUND There is a big contradiction in the medical literature regarding the relationship between atopy and contact hypersensitivity . Some research ers believe that atopy would prevent , whereas others believe that it would promote , the development of contact allergy . Possible causes of this confusion range from different study population s to different definitions of atopy . OBJECTIVE To evaluate the relationship between atopy and contact hypersensitivity in a well-defined general population sample using objective ly measurable markers . METHODS I studied 135 r and omly selected students from 5 vocational schools : 73 women and 62 men aged 18 to 19 years . The following atopy markers were tested : positive skin prick test results , positive Phadiatop test results , and total IgE levels greater than 120 kU/L. Contact hypersensitivity was detected by using patch tests . Statistical analyses included the Fisher exact test , the Mann-Whitney U test , and calculation of odds ratios . RESULTS At least 1 positive skin prick test result was found in 23.7 % ( 95 % confidence interval [ CI ] , 16.5%-30.9 % ) of study participants , positive Phadiatop test results were found in 20.0 % ( 95 % CI , 13.3%-26.7 % ) , and total IgE levels greater than 120 kU/L were found in 23.7 % ( 95 % CI , 16.5%-30.9 % ) . Positive patch test reactions were found in 28.1 % ( 95 % CI , 20.6%-35.7 % ) of participants , most frequently to thimerosal ( 18.5 % ; 95 % CI , 12.0%-25.1 % ) and nickel ( 9.6 % ; 95 % CI , 4.6%-14.6 % ) . For persons with atopy markers , odds ratios for contact hypersensitivity ranged from 1.0 to 3.2 , the highest being for nickel hypersensitivity among those with total IgE levels greater than 120 kU/L. None of these relationships were statistically significant . CONCLUSION Atopy and contact hypersensitivity are independent phenomena Few studies have so far addressed the prevalence and risk factors for contact sensitization in the general adult population ; however , many such studies have been conducted in hospitals . We present the prevalence of contact sensitization in a general adult population and its relationship to potential risk factors like smoking , ear piercing and atopic diseases . 1236 adults ( 44.2 % men and 55.8 % women ) were r and omly selected from a cross‐section of the population in Sør‐Varanger municipality , Norway , and patch tested with TRUE Test ( Pharmacia , Hillerød , Denmark ) . Contact sensitivity to at least 1 out of 24 allergens was found in 35.4 % of the women and in 14.8 % of the men . The most common allergens were nickel ( 17.6 % ) , cobalt ( 2.8 % ) , thiomersal ( 1.9 % ) , fragrance mix ( 1.8 % ) and colophony ( 1.2 % ) . All other allergens were observed in 1.0 % or less . In women , ear piercing was an important risk factor for nickel sensitization . No such significant correlation was seen in men [ in women relative risk ( RR ) = 3.30 , 95 % confidence interval ( CI ) = 2.01–5.43 , and in men RR = 1.82 , 95 % CI = 0.66–5.00 ] , and contact sensitivity was associated with atopic dermatitis ( AD ) [ adjusted odds ratio ( OR ) = 1.58 , 95 % CI = 1.04–2.40 ] and smoking ( adjusted OR = 1.42 , 95 % CI = 1.01–1.99 ) in women but not in men . The prevalence of contact sensitivity was common in this general population , especially in women . Smoking and AD might be a risk factor for contact sensitization This is a report on a comparative study of the reactivity of TRUE test and Finn Chamber patch test techniques . 413 patients attending a contact dermatitis clinic in Singapore were simultaneously patch tested with panels 1 and 2 of the TRUE test st and ard series and with corresponding allergens ( Hermal . Hamburg ) using Finn Chambers . The left/right application of the TRUE test and Finn Chambers was r and omized . The concordance of positive patch test reactions to the 2 test techniques was studied The number of patient with positive ructions was 38 % and 42 % for TRUE Test and Finn Chamber techniques , respectively ( n.s . ) . The overall concordance of positive patch test reactions was 64 % , ( 209/328 ) 13 % ( 42/128 ) of positive reactions appeared on TRUE Test only and 24 % ( 77 % 328 ) on Finn Chamber only . When only relevant positive reactions were considered , the concordance fate was 67 % ; 11 6 % Of positive reactions appeared on TRUE Test only and 21 % on Finn Chamber only . Positive reactions to p‐phenylenediamine ( PPD ) and neomycin were more frequent with the Finn Chamber technique than with TRUE Test , i e. , false negative reactions to PPD and neomyein were more likely to occur with TRUE Test . It appeared that the TRUE Test and Finn Chamber techniques were comparable when used for patch testing However false negative and false positive patch test reactions can occur when using either technique In 1990 and 1998 15 - 41-year-old people were patch-tested in 2 cross-sectional studies of r and om sample s of the population in the western part of Copenhagen County , Denmark . In 1990 , 290 subjects and in 1998 , 469 subjects were patch-tested . The participation rates were 69 % and 51 % , respectively . Contact sensitivity to one or more haptens was found in 15.9 % and 18.6 % in 1990 and 1998 , respectively . Nickel sensitivity is still the most common contact sensitivity . The risk of contact sensitivity to the cosmetic-related haptens included in the series ( formaldehyde was not included ) increased significantly from 2.4 % in 1990 to 5.8 % in 1998 ( odds ratio 2.44 , 95 % confidence interval 1.04 - 5.73 ) . The prevalence of contact sensitivity to cosmetic-related allergens has been doubled between 1990 and 1998 The aim of the present study was to investigate the relationship between patients ' own recognition of skin problems using consumer products and the results of patch testing with markers of fragrance sensitization . Eight hundred and eighty-four consecutive eczema patients , 18 - 69 years of age , filled in a question naire prior to patch testing with the European st and ard series . The question naire contained questions about skin symptoms from the use of scented and unscented products as well as skin reactions from contact with spices , flowers and citrus fruits that could indicate fragrance sensitivity . A highly significant association was found between reporting a history of visible skin symptoms from using scented products and a positive patch test to the fragrance mix , whereas no such relationship could be established to the Peru balsam in univariate or multivariate analysis . Our results suggest that the role of Peru balsam in detecting relevant fragrance contact allergy is limited , while most fragrance mix-positive patients are aware that the use of scented products may cause skin problems BACKGROUND Fragrances are the first or second most common cause of contact allergy in dermatitis patients . OBJECTIVE The aim of this study was to identify risk products for fragrance contact allergy . METHODS The design was a case-control study with a case group of 78 fragrance-mix-positive eczema patients and two control groups , one consisting of 1,279 subjects selected as a r and om sample of the general population and the other consisting of 806 fragrance-mix-negative eczema patients . The identification of risk products was based on the patients ' histories of rash to scented products . Analysis of the associations between first-time rash caused by different specified product categories and fragrance mix sensitivity was performed using logistic regression . RESULTS It was found that first-time rash caused by deodorant sprays and /or perfumes were related to fragrance contact allergy in a comparison with both control groups . The risk ( odds ratio ) of being diagnosed as fragrance allergic was 2.3 to 2.9 greater in cases of a history of first-time rash to deodorant sprays and 3.3 to 3.4 greater in cases of a history of rash to perfumes than if no such history were present . First-time rash to cleansing agents , deodorant sticks , or h and lotions was also statistically significant but only in comparison with one of the control groups . CONCLUSION Safety evaluation of fragrance material s used in perfumes and deodorant sprays should be performed with special attention |
2,397 | 31,713,918 | Provision of pharmaceutical care , effective multidisciplinary working and care home staff training represented the main areas of practical knowledge .
This study provides insight into potential codified and practical knowledge requirements for pharmacists assuming responsibility for the provision of pharmaceutical care within care homes . | OBJECTIVES To develop a training programme to enable pharmacists with prescribing rights to assume responsibility for the provision of pharmaceutical care within care homes , a systematic review and narrative synthesis was undertaken to identify reported approaches to training pharmacists and use this literature to identify potential knowledge requirements . | Introduction : Care home residents are at particular risk from medication errors , and our objective was to determine the prevalence and potential harm of prescribing , monitoring , dispensing and administration errors in UK care homes , and to identify their causes . Methods : A prospect i ve study of a r and om sample of residents within a purposive sample of homes in three areas . Errors were identified by patient interview , note review , observation of practice and examination of dispensed items . Causes were understood by observation and from theoretically framed interviews with home staff , doctors and pharmacists . Potential harm from errors was assessed by expert judgement . Results : The 256 residents recruited in 55 homes were taking a mean of 8.0 medicines . One hundred and seventy-eight ( 69.5 % ) of residents had one or more errors . The mean number per resident was 1.9 errors . The mean potential harm from prescribing , monitoring , administration and dispensing errors was 2.6 , 3.7 , 2.1 and 2.0 ( 0 = no harm , 10 = death ) , respectively . Contributing factors from the 89 interviews included doctors who were not accessible , did not know the residents and lacked information in homes when prescribing ; home staff ’s high workload , lack of medicines training and drug round interruptions ; lack of team work among home , practice and pharmacy ; inefficient ordering systems ; inaccurate medicine records and prevalence of verbal communication ; and difficult to fill ( and check ) medication administration systems . Conclusions : That two thirds of residents were exposed to one or more medication errors is of concern . The will to improve exists , but there is a lack of overall responsibility . Action is required from all concerned Objectives To compare the effectiveness of pharmacist medication review , with or without pharmacist prescribing , with st and ard care , for patients with chronic pain . Design An exploratory r and omised controlled trial . Setting Six general practice s with prescribing pharmacists in Grampian ( 3 ) and East Anglia ( 3 ) . Participants Patients on repeat prescribed pain medication ( 4815 ) were screened by general practitioners ( GPs ) , and mailed invitations ( 1397 ) . 196 were r and omised and 180 ( 92 % ) completed . Exclusion criteria included : severe mental illness , terminally ill , cancer related pain , history of addiction . R and omisation and intervention Patients were r and omised using a remote telephone service to : ( 1 ) pharmacist medication review with face-to-face pharmacist prescribing ; ( 2 ) pharmacist medication review with feedback to GP and no planned patient contact or ( 3 ) treatment as usual ( TAU ) . Blinding was not possible . Outcome measures Outcomes were the SF-12v2 , the Chronic Pain Grade ( CPG ) , the Health Utilities Index 3 and the Hospital Anxiety and Depression Scale ( HADS ) . Outcomes were collected at 0 , 3 and 6 months . Results In the prescribing arm ( n=70 ) two patients were excluded/nine withdrew . In the review arm ( n=63 ) one was excluded/three withdrew . In the TAU arm ( n=63 ) four withdrew . Compared with baseline , patients had an improved CPG in the prescribing arm , 47.7 % ( 21/44 ; p=0.003 ) and in the review arm , 38.6 % ( 17/44 ; p=0.001 ) , but not the TAU group , 31.3 % ( 15/48 ; ns ) . The SF-12 Physical Component Score showed no effect in the prescribing or review arms but improvement in TAU ( p=0.02 ) . The SF-12 Mental Component Score showed no effect for the prescribing or review arms and deterioration in the TAU arm ( p=0.002 ) . HADS scores improved within the prescribing arm for depression ( p=0.022 ) and anxiety ( p=0.007 ) , between groups ( p=0.022 and p=0.045 , respectively ) . Conclusions This is the first r and omised controlled trial of pharmacist prescribing in the UK , and suggests that there may be a benefit for patients with chronic pain . A larger trial is required . Trial registration : www.is rct n.org/IS RCT N06131530 . Medical Research Council funding OBJECTIVES To assess the effect of a Screening Tool of Older Persons potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment ( STOPP/START ) medication intervention on clinical and economic outcomes . DESIGN Parallel-group r and omized trial . SETTING Chronic care geriatric facility . PARTICIPANTS Residents aged 65 and older prescribed with at least one medication ( N = 359 ) were r and omized to receive usual pharmaceutical care or undergo medication intervention . INTERVENTION Screening medications with STOPP/START criteria followed up with recommendations to the chief physician . MEASUREMENTS The outcome measures assessed at the initiation of the intervention and 1 year later were number of hospitalizations and falls , Functional Independence Measure ( FIM ) , quality of life ( measured using the Medical Outcomes Study 12-item Short-Form Health Survey ) , and costs of medications . RESULTS The average number of drugs prescribed was significantly lower in the intervention than in the control group after 1 year ( P < .001 ) . The average drug costs in the intervention group decreased by 103 shekels ( US$ 29 ) per participant per month ( P < .001 ) . The average number of falls in the intervention group dropped significantly ( P = .006 ) . Rates of hospitalization , FIM scores , and quality of life measurements were similar for both groups . CONCLUSION Implementation of STOPP/START criteria reduced the number of medications , falls , and costs in a geriatric facility . Their incorporation in those and similar setting s is recommended OBJECTIVES Evaluate whether implementing of pharmacy-led psychopharmacology rounds in a nursing facility will improve the rate of antipsychotic use . DESIGN Single-center , prospect i ve ; medication use evaluation ( MUE ) . SETTING Rutl and Nursing Home , Brooklyn , New York . PARTICIPANTS Nursing facility residents , excluding the pediatric unit . INTERVENTIONS Weekly interdisciplinary psychopharmacology rounds that include : clinical pharmacists , nurse managers , medical director , social workers , and administration . Antipsychotics were analyzed for all residents for appropriateness of use , proper documentation , and adequate monitoring . MAIN OUTCOME MEASURE Assess the overall rate of reduction of antipsychotic use after implementation of psychopharmacology rounds . Secondary outcomes assessed improvements in monitoring and documentation for residents on antipsychotics . RESULTS A total of 81 residents were evaluated over the six-month MUE . Of those residents , 20 had their antipsychotics discontinued , and 11 had their antipsychotics tapered . The overall use of antipsychotics decreased from 14.6 % ( 62/422 ) to 12.2 % ( 50/411 ) ( P = 0.285 ) . Compliance with indications generally approved by the Centers for Medicare & Medicaid Services improved from 65 % ( 37/57 ) to 85 % ( 46/54 ) ( P = 0.008 ) . Matching indications on the psychiatry consult and the medication order improved from 58 % ( 33/57 ) to 80 % ( 43/54 ) ( P = 0.015 ) . Metabolic laboratory monitoring improved from 58 % ( 33/57 ) to 83 % ( 45/54 ) ( P = 0.003 ) . Improvements in timeliness of psychiatry and ophthalmology consults were not statistically significant . CONCLUSION Implementing interdisciplinary psycho-pharmacology rounds in a nursing facility result ed in a reduction of inappropriate antipsychotic use and improved monitoring and documentation 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 OBJECTIVE to measure the impact of pharmacist-conducted clinical medication review with elderly care home residents . DESIGN r and omised controlled trial of clinical medication review by a pharmacist against usual care . SETTING sixty-five care homes for the elderly in Leeds , UK . PARTICIPANTS a total of 661 residents aged 65 + years on one or more medicines . INTERVENTION clinical medication review by a pharmacist with patient and clinical records . Recommendations to general practitioner for approval and implementation . Control patients received usual general practitioner care . MAIN OUTCOME MEASURES primary : number of changes in medication per participant . Secondary : number and cost of repeat medicines per participant ; medication review rate ; mortality , falls , hospital admissions , general practitioner consultations , Barthel index , St and ardised Mini-Mental State Examination ( SMMSE ) . RESULTS the pharmacist review ed 315/331 ( 95.2 % ) patients in 6 months . A total of 62/330 ( 18.8 % ) control patients were review ed by their general practitioner . The mean number of drug changes per patient were 3.1 for intervention and 2.4 for control group ( P < 0.0001 ) . There were respectively 0.8 and 1.3 falls per patient ( P < 0.0001 ) . There was no significant difference for GP consultations per patient ( means 2.9 and 2.8 in 6 months , P = 0.5 ) , hospitalisations ( means 0.2 and 0.3 , P = 0.11 ) , deaths ( 51/331 and 48/330 , P = 0.81 ) , Barthel score ( 9.8 and 9.3 , P = 0.06 ) , SMMSE score ( 13.9 and 13.8 , P = 0.62 ) , number and cost of drugs per patient ( 6.7 and 6.9 , P = 0.5 ) ( pounds sterling 42.24 and pounds sterling 42.94 per 28 days ) . A total of 75.6 % ( 565/747 ) of pharmacist recommendations were accepted by the general practitioner ; and 76.6 % ( 433/565 ) of accepted recommendations were implemented . CONCLUSIONS general practitioners do not review most care home patients ' medication . A clinical pharmacist can review them and make recommendations that are usually accepted . This leads to substantial change in patients ' medication regimens without change in drug costs . There is a reduction in the number of falls . There is no significant change in consultations , hospitalisation , mortality , SMMSE or Barthel scores Aim of study : This study sought to determine whether multidisciplinary case conference review s improved outcomes for nursing home residents , and the effects of this team approach to resident care on carers , including the h and s-on carers employed by the nursing home , and health professionals . Method : 245 residents of three Canberra nursing homes were enrolled in this non-r and omised controlled trial . The intervention consisted of sessions of three case conference review s held between 10/4sol;96 and 4sol;12sol;96 . These sessions were attended by the General Practitioners ( GPs ) of the residents discussed , the GP project officer from the ACT Division of General Practice , a clinical pharmacist , senior nursing staff , other health professionals eg physiotherapist , and occasionally the resident concerned or their representative . At each review , a case presentation by the resident 's GP was followed by a multidisciplinary discussion of all aspects , medical and non-medical , of the resident 's care . The review concluded with a management plan for the resident . In total 75 residents were review ed . Main outcome measures : Medication use and cost , and mortality . Results : One month after the review s were completed comparisons between those who were review ed and those who were not showed non-significant reductions in medication orders , medication cost , and mortality in the review ed group . Many of the 92 recommendations in the management plans that were carried out benefited the residents ( n=37 ) and /or carers ( n=24 ) . The responses of the GPs and the Directors of Nursing to the review s were overwhelmingly positive . Conclusion : Recommendations arising from multidisciplinary case conferences were carried out to the benefit of patients and carers . Given the support shown by key stakeholders , multidisciplinary conferences should be used more OBJECTIVE To assess the importance and performance of consultant pharmacist services delivered before and after an intervention to detect and manage adverse drug events among nursing facility residents . DESIGN Before and after intervention survey of physicians participating in a r and omized , controlled trial . SETTING Four nonprofit , academically affiliated nursing facilities . PARTICIPANTS Attending physicians providing nursing facility care who were r and omized to intervention or control groups . INTERVENTIONS Within the intervention arm , consultant pharmacists provided academic detailing in which trained health care professionals visit practicing physicians in their offices and present the most up-to- date clinical information . Physicians responded to alerts from a medication monitoring system , adjudicated system alerts for adverse drug events ( ADEs ) , and provided structured recommendations about ADE management . MAIN OUTCOME MEASURES We compared physicians ' assessment s of the importance and performance of consultant pharmacist services before and after the trial intervention in the intervention and control groups . RESULTS In the intervention group , ratings of importance increased for all 24 survey questions , and 5 of the changes were statistically significant ( P < 0.05 ) . In the control group , ratings of importance increased for 16 questions , and none of the changes were statistically significant . In the intervention group , ratings of performance increased for all 24 questions , and 20 of the changes were statistically significant . In the control group , ratings of performance increased for 16 questions , and none of the changes was statistically significant . CONCLUSION A multifaceted , consultant pharmacist-led intervention comprising academic detailing , computerized decision support , and structured communication framework can improve physicians ' assessment of importance and performance of consultant pharmacist services . ABBREVIATIONS ADE = Adverse drug event , M = Statistically significant mean , RCT = R and omized controlled trial , SBAR = Situation , Background , Discussion , Recommendation , SD = St and ard deviation OBJECTIVE To analyze the effect of using a pharmacist-initiated antipsychotic use survey tool on improving nursing home compliance for appropriate antipsychotic use in patients with dementia . DESIGN Prospect i ve chart review study . SETTING Two nursing homes in Marin County , California . PARTICIPANTS Nursing home residents diagnosed with dementia and receiving antipsychotic medication . INTERVENTION Pharmacist performing survey tool screening for appropriate antipsychotic use based on Centers for Medicare & Medicaid Services guidelines and using information from the survey tool as part of the pharmacist recommendations to the prescriber . MAIN OUTCOME MEASURES Number of pharmacist recommendations indicated by the survey tool for antipsychotic gradual dose reduction ( GDR ) or discontinuation that are accepted by prescribers . Number and percent of residents on antipsychotic medication per nursing home prior and throughout the study period . RESULTS Of the final 20 study population residents , 12 were survey-recommended for GDR or antipsychotic discontinuation . Within the 12 recommendations , four were accepted by prescribers from one of the two nursing homes . Decline in antipsychotic use was observed in the same nursing home throughout the seven months from 28 residents ( 21 % ) to 19 residents ( 14 % ) . No significant difference in antipsychotic use before and after intervention was observed in the other nursing home . Overall feedback reported intervention helpful and requested continued pharmacist involvement . CONCLUSION Nursing home compliance improved and antipsychotic use declined during pharmacist intervention at one nursing home . Multiple factors may be involved in pharmacist recommendation acceptance OBJECTIVES To determine the extent to which the use of a clinical informatics tool that implements prospect i ve monitoring plans reduces the incidence of potential delirium , falls , hospitalizations potentially due to adverse drug events , and mortality . DESIGN R and omized cluster trial . SETTING Twenty-five nursing homes serviced by two long-term care pharmacies . PARTICIPANTS Residents living in nursing homes during 2003 ( 1,711 in 12 intervention ; 1,491 in 13 usual care ) and 2004 ( 1,769 in 12 intervention ; 1,552 in 13 usual care ) . INTERVENTION The pharmacy automatically generated Geriatric Risk Assessment MedGuide ( GRAM ) reports and automated monitoring plans for falls and delirium within 24 hours of admission or as part of the normal time frame of federally m and ated drug regimen review . MEASUREMENTS Incidence of potential delirium , falls , hospitalizations potentially due to adverse drug events , and mortality . RESULTS GRAM triggered monitoring plans for 491 residents . Newly admitted residents in the intervention homes experienced a lower rate of potential delirium onset than those in usual care homes ( adjusted hazard ratio (HR)=0.42 , 95 % confidence interval (CI)=0.35 - 0.52 ) , overall hospitalization ( adjusted HR=0.89 , 95 % CI=0.72 - 1.09 ) , and mortality ( adjusted HR=0.88 , 95 % CI=0.66 - 1.16 ) . In longer stay residents , the effects of the intervention were attenuated , and all estimates included unity . CONCLUSION Using health information technology in long-term care pharmacies to identify residents who might benefit from the implementation of prospect i ve medication monitoring care plans when complex medication regimens carry potential risks for falls and delirium may reduce adverse effects associated with appropriate medication use OBJECTIVE To determine if pharmacist intervention can decrease the use of inappropriate sedative/hypnotics in the elderly population in the long-term care facility setting . DESIGN A multicenter , prospect i ve chart review of sedative/hypnotic use for insomnia among long-term care facility residents . SETTING Eleven regional long-term care facilities in Northeastern Tennessee . PARTICIPANTS Long-term care facility residents older than 65 years of age , with confirmed insomnia diagnoses and no history of seizure or recent psychotropic gradual-dose reduction attempts . INTERVENTION Consultant pharmacist recommendations to decrease inappropriate use of sedative/hypnotics . MAIN OUTCOME MEASURE Acceptance rates for discontinuation/tapering of the selected sedative/hypnotics . RESULTS A total of 36 patients were enrolled in the study based on inclusion /exclusion criteria . Overall , 39 interventions were performed . Gradual dose reductions/ discontinuation of select sedative/hypnotics were accepted for 19 residents ( 48.7 % ) . Of the other recommendations , 8 ( 20.5 % ) were denied and 12 ( 30.8 % ) were left unanswered . Primary reasons for denial included family refusal , satisfactory response to current dose , and requirement of increased dose as a result of worsening insomnia . CONCLUSIONS Overall , pharmacist intervention can have a meaningful impact on reducing inappropriate sedative/ hypnotic use in the elderly population through concise , evidence -based recommendations to physicians BACKGROUND Older people in nursing and residential homes often have complex disabilities and behavioural disturbances . Recent publicity has highlighted the dangers of medication in this group , and controls over prescribing have been suggested . AIMS To investigate the effect of a review of medication by a pharmacist . METHOD An 8-month prospect i ve trial of an active medication review by a pharmacist was carried out on 330 residents in nursing homes in Manchester . RESULTS The intervention group experienced greater deterioration in cognitive function and behavioural disturbance than the control group , but the changes in depression and quality of life were similar for both groups . The number of drugs prescribed fell in the intervention group , but not in the control group , with a corresponding saving in drug costs . The number of deaths was significantly smaller in the intervention homes during the intervention period ( 4 v. 14 ) but not overall during the study period as a whole ( 26 v. 28 ) . CONCLUSION This clinical intervention reduced the number of medicines prescribed to elderly people in nursing homes , with minimal impact on their morbidity and mortality Background — Hypertension control rates remain suboptimal . Pharmacists ’ scope of practice is evolving , and their position in the community may be ideal for improving hypertension care . We aim ed to study the impact of pharmacist prescribing on blood pressure ( BP ) control in community-dwelling patients . Methods and Results — We design ed a patient-level , r and omized , controlled trial , enrolling adults with above-target BP ( as defined by Canadian guidelines ) through community pharmacies , hospitals , or primary care teams in 23 communities in Alberta . Intervention group patients received an assessment of BP and cardiovascular risk , education on hypertension , prescribing of antihypertensive medications , laboratory monitoring , and monthly follow-up visits for 6 months ( all by their pharmacist ) . Control group patients received a wallet card for BP recording , written hypertension information , and usual care from their pharmacist and physician . Primary outcome was the change in systolic BP at 6 months . A total of 248 patients ( mean age , 64 years ; 49 % male ) were enrolled . Baseline mean±SD systolic/diastolic BP was 150±14/84±11 mm Hg . The intervention group had a mean±SE reduction in systolic BP at 6 months of 18.3±1.2 compared with 11.8±1.9 mm Hg in the control group , an adjusted difference of 6.6±1.9 mm Hg ( P=0.0006 ) . The adjusted odds of patients achieving BP targets was 2.32 ( 95 % confidence interval , 1.17–4.15 in favor of the intervention ) . Conclusions — Pharmacist prescribing for patients with hypertension result ed in a clinical ly important and statistically significant reduction in BP . Policy makers should consider an exp and ed role for pharmacists , including prescribing , to address the burden of hypertension . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00878566 BACKGROUND Poorly executed transfers of older patients from hospitals to long-term care facilities carry the risk of fragmentation of care , poor clinical outcomes , inappropriate use of emergency department services , and hospital readmission . OBJECTIVE This study was conducted to assess the impact of adding a pharmacist transition coordinator on evidence -based medication management and health outcomes in older adults undergoing first-time transfer from a hospital to a long-term care facility . METHODS This r and omized , single-blind , controlled trial enrolled hospitalized older adults awaiting transfer to a long-term residential care facility for the first time . Patients were r and omized either to receive the services of the pharmacist transition coordinator ( intervention group ) or to undergo the usual hospital discharge process ( control group ) . The intervention included medication-management transfer summaries from hospitals , timely coordinated medication review s by accredited community pharmacists , and case conferences with physicians and pharmacists . The primary outcome was the quality of prescribing , measured using the Medication Appropriateness Index ( MAI ) . Secondary outcomes were emergency department visits , hospital readmissions , adverse drug events , falls , worsening mobility , worsening behaviors , increased confusion , and worsening pain . RESULTS One hundred ten older adults ( 67 women , 43 men ; mean [ SD ] age , 82.7 [ 6.4 ] years ) were recruited from 3 metropolitan hospitals and assigned to 85 metropolitan long-term care facilities . Fifty-six patients were r and omized to the intervention group and 54 to the control group ; 44 patients in each group were evaluable at 8-week follow-up . There were no significant differences in baseline characteristics between treatment groups , with the exception of the number of medications discontinued during hospitalization : a mean of 1.1 more drugs was discontinued in the control group compared with the intervention group ( P = 0.011 ) . The majority of patients ( 35 [ 62.5 % ] in the intervention group , 41 [ 76.0 % ] in the control group ) changed physicians as part of the transition to a long-term care facility . At 8-week follow-up , there was no change in MAI from baseline in the intervention group , whereas it had worsened in the control group ( mean [ 95 % CI ] , 2.5 [ 1.4 - 3.7 ] vs 6.5 [ 3.9 - 9.1 ] , respectively ; P = 0.007 ) . Patients who received the intervention and were alive at follow-up exhibited a significant protective effect of the intervention against worsening pain ( relative risk ratio [ 95 % CI ] , 0.55 [ 0.32 - 0.94 ] ; P = 0.023 ) and hospital usage ( i.e. , the combination of emergency department visits and hospital readmissions ) ( 0.38 [ 0.15 - 0.99 ] ; P = 0.035 ) , but did not differ from control patients in terms of adverse drug events ( 1.05 [ 0.66 - 1.68 ] ) , falls ( 1.19 [ 0.71 - 1.99 ] ) , worsening mobility ( 0.39 [ 0.13 - 1.15 ] ) , worsening behaviors ( 0.52 [ 0.25 - 1.10 ] ) , or increased confusion ( 0.59 [ 0.28 - 1.22 ] ) . When data for patients who had died were included , the intervention had no effect on hospital usage in all patients ( 0.58 [ 0.28 - 1.21 ] ) . CONCLUSIONS Older people transferring from hospital to a long-term care facility are vulnerable to fragmentation of care and adverse events . In this study , use of a pharmacist transition coordinator improved aspects of inappropriate use of medicines across health sectors Abstract Medication use in nursing homes is often suboptimal . This study investigated the impact of a pharmacist-conducted medication review on the appropriateness of prescribing for Belgian nursing home residents . We conducted a 6-month controlled , non-r and omized study in two nursing homes ( one intervention and one control nursing home ) . Sixty-nine residents completed the study in the intervention group ( 92 residents were included ) . For the control group , that were 79 residents ( 100 residents were included ) . Primary outcome was the appropriateness of prescribing , assessed by a set of vali date d quality indicators . At baseline , this study detected three main problems associated with the appropriateness of medication use : ( i ) the Medication Appropriateness Index ( MAI ) could be improved ( continuation of no longer indicated medication was the most common problem ) , ( ii ) potential overuse was present in about half of the group , and ( iii ) potential underuse was present in about 30 % of the sample . Despite this , our pharmacist-conducted medication review only modestly improved the appropriateness of prescribing . This may be attributed to the low implementation rate of the pharmacist recommendations OBJECTIVES To evaluate the cost-effectiveness of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Irel and ( Fleetwood NI Study ) . DESIGN Economic evaluation alongside a cluster r and omized controlled trial . SETTING Nursing homes in NI 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=253 ; 128 intervention , 125 control ) and who had full re source use data at 12 months . INTERVENTION Trained pharmacists review ed intervention home residents ' clinical and prescribing information for 12 months , applied an algorithm that guided them in assessing the appropriateness of psychoactive medication , and worked with prescribers ( general practitioners ) to make changes . The control homes received usual care in which there was no pharmacist intervention . MEASUREMENTS The proportion of residents prescribed one or more inappropriate psychoactive medications ( according to st and ardized protocol s ) , costs , and a cost-effectiveness acceptability curve . The latter two outcomes are the focus for this article . RESULTS The proportions of residents receiving inappropriate psychoactive medication at 12 months in the intervention and control group were 19.5 % and 50.4 % , respectively . The mean cost of healthcare re sources used per resident per year was $ 4,923 ( 95 % confidence interval (CI)=$4,206 - 5,640 ) for the intervention group and $ 5,053 ( 95 % CI=$4,328 - 5,779 ) for the control group . The probability of the intervention being cost-effective was high , even at low levels of willingness to pay to avoid a resident receiving inappropriately prescribed psychoactive medication . CONCLUSION The Fleetwood NI model of care was more cost-effective than usual care BACKGROUND efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care . We describe a case conference intervention involving a multidisciplinary team of health professionals . OBJECTIVES to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities . DESIGN cluster-r and omised controlled trial . SETTING ten high-level aged care facilities . PARTICIPANTS 154 residents with medication problems and /or challenging behaviours were selected for case conference by residential care staff . INTERVENTION two multidisciplinary case conferences involving the resident 's general practitioner , a geriatrician , a pharmacist and residential care staff were held at the nursing home for each resident . MEASUREMENTS outcomes were assessed at baseline and 3 months . The primary outcome was the Medication Appropriateness Index ( MAI ) . The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale . RESULTS 45 residents died before follow-up . Medication appropriateness improved in the intervention group [ MAI mean change 4.1 , 95 % confidence interval ( CI ) 2.1 - 6.1 ] compared with the control group ( MAI mean change 0.4 , 95 % CI -0.4 - 1.2 ; P < 0.001 ) . There was a significant reduction in the MAI for benzodiazepines ( mean change control -0.38 , 95 % CI -1.02 - 0.27 versus intervention 0.73 , 95 % CI 0.16 - 1.30 ; P = 0.017 ) . Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility . CONCLUSION multidisciplinary case conferences in nursing homes can improve care . Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing BACKGROUND Medication organisation devices ( MODs ) provide compartments for a patient 's medication to be organised into the days of the week and the recommended times the medication should be taken . AIM To define the optimal trial design for testing the clinical effectiveness and cost-effectiveness of MODs . DESIGN The feasibility study comprised a systematic review and focus groups to inform a r and omised controlled trial ( RCT ) design . The result ing features were tested on a small scale , using a 2 × 2 factorial design to compare MODs with usual packaging and to compare weekly with monthly supply . The study design was then evaluated . SETTING Potential participants were identified by medical practice s. PARTICIPANTS Aged over 75 years , prescribed at least three solid oral dosage form medications , unintentionally non-adherent and self-medicating . Participants were excluded if deemed by their health-care team to be unsuitable . INTERVENTIONS One of three MODs widely used in routine clinical practice supplied either weekly or monthly . OBJECTIVES To identify the most effective method of participant recruitment , to estimate the prevalence of intentional and unintentional non-adherence in an older population , to provide a point estimate of the effect size of MODs relative to usual care and to determine the feasibility and acceptability of trial participation . METHODS The systematic review included MOD studies of any design reporting medication adherence , health and social outcomes , re source utilisation or dispensing or administration errors . Focus groups with patients , carers and health-care professionals supplemented the systematic review to inform the RCT design . The result ing design was implemented and then evaluated through question naires and group discussion s with participants and health-care professionals involved in trial delivery . RESULTS Studies on MODs are largely of poor quality . The relationship between adherence and health outcomes is unclear . Of the limited studies reporting health outcomes , some reported a positive relationship while some reported increased hospitalisations associated with MODs . The pre-trial focus groups endorsed the planned study design , but suggested a minimum recruitment age of 50 - 60 years . A total of 35.4 % of patients completing the baseline question naire were excluded because they already used a MOD . Active recruitment yielded a higher consent rate , but passive recruitment was more cost-effective . The prevalence of intentional non-adherence was 24.7 % [ n = 71 , 95 % confidence interval ( CI ) 19.7 % to 29.6 % ] of participants . Of the remaining 76 participants , 46.1 % ( 95 % CI 34.8 % to 57.3 % ) were unintentionally non-adherent . There was no indication of a difference in adherence between the study arms . Participants reported a high level of satisfaction with the design . Five adverse/serious adverse events were identified in the MOD study arms and none was identified in the control arms . There was no discernible difference in health economic outcomes between the four study arms ; the mean intervention cost was £ 20 per month greater for MOD monthly relative to usual supply monthly . CONCLUSIONS MOD provision to unintentionally non-adherent older people may cause medication-related adverse events . The primary outcome for a definitive MOD trial should be health outcomes . Such a trial should recruit patients by postal invitation and recruit younger patients . FUTURE WORK A study examining the association between MOD initiation and adverse effects is necessary and a strategy to safely introduce MODs should be explored . A definitive study testing the clinical effectiveness and cost-effectiveness of MODs is also required . STUDY REGISTRATION Current Controlled Trials IS RCT N 30626972 and UKCRN 12739 . FUNDING This project was funded by National Institute for Health Research ( NIHR ) Health Technology Assessment Programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 50 . See the NIHR Journals Library website for further project information WHAT IS KNOWN AND OBJECTIVE With the ageing of the population also comes increasing comorbidities and the use of multiple medications and administration methods , along with greater susceptibility to adverse drug reactions . Dosage form modification to facilitate drug administration in older adults can be potentially problematic as altering the original licensed formulation can affect medication safety and efficacy . The reporting of adverse drug reactions and medication incidents is a key strategy in avoiding preventable adverse drug events for aged care residents . This study evaluated the effect of an on-site clinical pharmacist on reducing inappropriate dosage form modification and staff time spent on medication administration , and optimizing the documentation of drug allergies , adverse drug reactions and medication incidents . METHODS A pilot-controlled trial was performed in a purposive sample of two residential aged care homes . Both homes belonged to the same organization ; the study site had 104 beds and the control site had 100 beds . All permanent residents were eligible for inclusion in the study if written consent was provided . A residential care pharmacist position was implemented at the study site for six months , with a focus on performing medication review s and quality improvement activities . Observational audits of medication rounds were performed , and documentation relating to allergies , adverse drug reactions , and medication incidents was obtained from both sites before and after the pharmacist trial period . RESULTS At the study site , there was a significant reduction over the trial in the proportion of inappropriate dosage form modification ( from 24 % to 0 % of all dosage form modifications ; P < 0.01 ) . Mean time spent on medication rounds per resident reduced from 4.8 minutes per resident ( SD 1.1 ) to 3.2 minutes per resident ( SD 1.7 ) per round ( P < 0.05 ) . The incidence of previous allergy and adverse drug reaction documentation significantly improved from 77 % of residents pre- study to 100 % of residents post- study ( P < 0.01 ) . Mean monthly medication incident reports significantly improved from 13.3 ( SD 7.4 ) pre- study to 25.7 ( SD 10.8 ) post- study ( P < 0.05 ) . There was no change in these outcomes at the control site . WHAT IS NEW AND CONCLUSION Including a pharmacist in a residential aged care home can improve medication administration practice s by reducing inappropriate dosage form modification and staff time spent on medication administration rounds , and increasing the documentation of resident allergies , adverse drug reactions and medication incidents . These findings warrant further exploration in a large r and omized controlled trial Background and objective : The prevalence of potentially inappropriate prescribing ( PIP ) among nursing home ( NH ) residents is high . This study aim ed to investigate the acceptance and implementation of pharmacist recommendations based on a screening tool for PIP , the Ghent Older People 's Prescriptions community Pharmacy Screening (GheOP3S)-tool . Setting and method : Prospect i ve observational study in NH residents ( ≥ 70 years , using ≥ 5 medications ) with a 3-month follow-up period . A pharmacist screened the medication lists using the GheOP3S-tool and formulated recommendations to reduce PIP . The acceptance of recommendations discussed during face-to-face pharmacist-general practitioner ( GP ) meetings was recorded . Implementation was examined by comparing baseline and follow-up medication lists . A pre-post comparison of the number of chronic medications and GheOP3S- criteria ; the anticholinergic and sedative burden quantified by the Drug Burden Index ( DBI ) ; and medication costs was performed . Results : Screening with the GheOP3S-tool result ed in 168 pharmacist recommendations for 50 NH residents , mainly to stop ( 78.0 % ) and to substitute ( 14.3 % ) medications . Ninety-three % ( 156/168 ) of recommendations were considered relevant . GPs acceptance rate was 44.9 % . Fifty-four % of all accepted recommendations were implemented . At follow-up , the number of chronic medications ( p = 0.007 ) , and DBI scores ( p = 0.004 ) significantly differed from baseline . There was no significant decrease in the number of GheOP3S- criteria ( p = 0.075 ) and medication costs ( p > 0.05 ) . Conclusion : The acceptance and implementation of pharmacist recommendations were relatively low . Future studies should increase the involvement of patients and all health-care providers . Interdisciplinary collaboration with sufficient education for all disciplines and patients is essential Background Residents in care homes are often very frail , have complex medicine regimens and are at high risk of adverse drug events . It has been recommended that one healthcare professional should assume responsibility for their medicines management . We propose that this could be a pharmacist independent prescriber ( PIP ) . This feasibility study aim ed to test and refine the service specification and proposed study processes to inform the design and outcome measures of a definitive r and omised controlled trial to examine the clinical and cost effectiveness of PIPs working in care homes compared to usual care . Specific objectives included testing processes for participant identification , recruitment and consent and assessing retention rates ; determining suitability of outcome measures and data collection processes from care homes and GP practice s to inform selection of a primary outcome measure ; assessing service and research acceptability ; and testing and refining the service specification . Methods Mixed methods ( routine data , question naires and focus groups/interviews ) were used in this non-r and omised open feasibility study of a 3-month PIP intervention in care homes for older people . Data were collected at baseline and 3 months . One PIP , trained in service delivery , one GP practice and up to three care homes were recruited at each of four UK locations . For ten eligible residents ( ≥ 65 years , on at least one regular medication ) in each home , the PIP undertook management of medicines , repeat prescription authorisation , referral to other healthcare professionals and staff training . Outcomes ( falls , medications , resident ’s quality of life and activities of daily living , mental state and adverse events ) were described at baseline and follow-up and assessed for inclusion in the main study . Participants ’ views post-intervention were captured in audio-recorded focus groups and semi-structured interviews . Transcripts were thematically analysed . Results Across the four locations , 44 GP practice s and 16 PIPs expressed interest in taking part ; all care homes invited agreed to take part . Two thirds of residents approached consented to participate ( 53/86 ) . Forty residents were recruited ( mean age 84 years ; 61 % ( 24 ) were female ) , and 38 participants remained at 3 months ( two died ) . All GP practice s , PIPs and care homes were retained . The number of falls per participating resident was selected as the primary outcome , following assessment of the different outcome measures against predetermined criteria . The chosen secondary outcomes / outcome measures include total falls , drug burden index ( DBI ) , hospitalisations , mortality , activities of daily living ( Barthel ( proxy ) ) and quality of life ( ED-5Q-5 L ( face-to-face and proxy ) ) and selected items from the STOPP/START guidance that could be assessed without need for clinical judgement . No adverse drug events were reported . The PIP service was generally well received by the majority of stakeholders ( care home staff , GPS , residents , relatives and other health care professionals ) . PIPs reported feeling more confident implementing change following the training but reported challenges accommodating the new service within their existing workload . Conclusion Implementing a PIP service in care homes is feasible and acceptable to care home residents , staff and clinicians . Findings have informed refinements to the service specification , PIP training , recruitment to the future RCT and the choice of outcomes and outcome measures . The full RCT with internal pilot started in February 2016 and results are expected to be available in mid late 2020 OBJECTIVES To compare the cost-effectiveness of a pharmacotherapy follow-up for elderly nursing home ( NH ) residents with that of usual care . DESIGN Prospect i ve observational study with a concurrent control group conducted over 12 months . SETTING Fifteen NHs in And alusia assigned to control ( n = 6 ) or intervention ( n = 9 ) . PARTICIPANTS Residents aged 65 and older . INTERVENTION Pharmacotherapy follow-up . MEASUREMENTS Negative outcomes associated with medication , health-related quality of life , cost , quality -adjusted life-year ( QALY ) , and incremental cost-effectiveness ratio ( ICER ) . ICERs were estimated for three scenarios : unadjusted cost per QALY ( first scenario ) , costs adjusted for baseline prescribed medication and QALYs adjusted for baseline utility score ( second scenario ) , and costs and QALYs adjusted for a fuller set of baseline characteristics ( third scenario ) . RESULTS Three hundred thirty-two elderly residents were enrolled : 122 in the control group and 210 in the intervention group . The general practitioner accepted 88.7 % ( 274/309 ) of pharmacist recommendations . Pharmacist interventions reduced the average number of prescribed medication by 0.47 drugs ( P < .001 ) , whereas the average prescribed medication increased by 0.94 drugs in the control group ( P < .001 ) . Both groups reported a lower average EuroQol-5D utility score after 12 months ( intervention , -0.0576 , P = .002 ; control , -0.0999 , P = .003 ) . For the first scenario , usual care dominated pharmacotherapy follow-up ( was less effective and more expensive ) . Adjusted ICERs were € 3,899/QALY ( $ 5,002/QALY ) for the second scenario and € 6,574/QALY ( $ 8,433/QALY ) for the third scenario . For a willingness to pay of € 30,000/QALY ( $ 38,487/QALY ) , the probabilities of the pharmacotherapy follow-up being cost-effective were 35 % for the first scenario , 78 % for the second , and 76 % for the third . CONCLUSION Pharmacotherapy follow-up is considered cost-effective for elderly NH residents in Spain Objective : Polypharmacy and adverse drug reactions are frequent and important among older people . Few clinical trials have evaluated systematic withdrawal of medications among older people . This small , open , study was conducted to determine the feasibility of a r and omized controlled deprescribing trial . Methods : Ten volunteers living in the community ( recruited by media advertising ) and 25 volunteers living in residential aged-care facilities ( RCFs ) were r and omized to intervention or control groups . The intervention was gradual withdrawal of one target medication . The primary outcome was the number of intervention participants in whom medication withdrawal could be achieved . Other outcomes measures were quality of life , medication adherence , sleep quality , and cognitive impairment . Results : Participants were aged 80 ± 11 years and were taking 9 ± 2 medications . Fifteen participants commenced medication withdrawal and all ceased or reduced the dose of their target medication . Two subjects withdrew ; one was referred for clinical review , and one participant declined further dose reductions . Conclusions : A r and omized controlled trial of deprescribing was acceptable to participants . Recruitment in RCFs is feasible . Definitive trials of deprescribing are required |
2,398 | 32,289,164 | Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding . | Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity , but it could also increase the risk of major bleeding .
We systematic ally review ed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism ( PE ) and /or deep venous thrombosis ( DVT ) . | Treatment with heparin or streptokinase was allocated r and omly to 30 patients with life-threatening pulmonary embolism verified by angiography . Treatment was given for 72 hours and pulmonary angiography was repeated . There was significantly greater ( P < 0·001 ) evidence of thrombolysis in those patients treated with streptokinase compared with those treated with heparin . The reduction of systolic and mean pulmonary arterial pressures was also significantly greater ( P < 0·05 and P < 0·02 respectively ) in the streptokinase group . Seven patients failed to complete 72 hours of the trial treatment : five successfully underwent pulmonary embolectomy . Six of these “ failures ” had initial pulmonary angiographic scores of 24 or more and systemic systolic blood pressure recordings of 100 mm Hg or less . Patients with these features should probably be considered for pulmonary embolectomy as the initial treatment . A febrile reaction commonly occurred in the streptokinase group ; otherwise side effects were no more common than in the heparin group Dissolution of pulmonary emboli with heparin and urokinase is ascribed , respectively , to anticoagulation and fibrinolysis . Since truly independent assessment of these effects in man is lacking , we administered each drug alone . Fibrinogen and plasminogen plasma levels and the resolution of pulmonary emboli were measured in three r and omized groups of 10 patients each : groups A and C infused with small repeated doses of urokinase and a large single dose of urokinase , respectively , and group B who received heparin . After 6 h of treatment , fibrinogen fell in all the groups , while , after 12 h , remained equally reduced in groups A and B and declined further in group C. Plasminogen behaved similarly . Up to 60 h , statistical analysis showed that these effects were related to timing and amounts of urokinase and heparin infusion . These observations suggest that heparin may induce a lytic state . As to signs of pulmonary emboli resolution , no differences between groups were found in lung perfusion and gas exchange recovery at any time ( from 1 day to 1 year ) and in pulmonary artery pressure reduction at 1 week . The greater angiographic and scintigraphic recovery observed with urokinase , versus heparin alone , after 1 day of treatment in the Urokinase Pulmonary Embolism Trial may be ascribed to a synergistic effect with urokinase of heparin administered during the diagnostic work-out . The indications of heparin and urokinase should be evaluated in the light of these results BACKGROUND Acute pulmonary embolism ( PE ) can worsen quality of life due to persistent dyspnea or exercise intolerance . OBJECTIVE Test if tenecteplase increases the probability of a favorable composite patient-oriented outcome after submassive PE . METHODS Normotensive patients with PE and right ventricular ( RV ) strain ( by echocardiography or biomarkers ) were enrolled from eight hospitals . All patients received low-molecular-weight heparin followed by r and om assignment to either a single weight-based bolus of tenecteplase or placebo , administered in a double-blinded fashion . The primary composite outcome included : ( i ) death , circulatory shock , intubation or major bleeding within 5 days or ( ii ) recurrent PE , poor functional capacity ( RV dysfunction with either dyspnea at rest or exercise intolerance ) or an SF36 ( ® ) Physical Component Summary ( PCS ) score < 30 at 90-day follow-up . RESULTS Eighty-three patients were r and omized ; 40 to tenecteplase and 43 to placebo . The trial was terminated prematurely . Within 5 days , adverse outcomes occurred in three placebo-treated patients ( death in one and intubation in two ) and one tenecteplase-treated patient ( fatal intracranial hemorrhage ) . At 90 days , adverse outcomes occurred in 13 unique placebo-treated patients and five unique tenecteplase-treated patients Thus , 16 ( 37 % ) placebo-treated and six ( 15 % ) tenecteplase-treated patients had at least one adverse outcome ( exact two-sided P = 0.017 ) . CONCLUSIONS Treatment of patients with submassive pulmonary embolism with tenecteplase was associated with increased probability of a favorable composite outcome BACKGROUND The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial . METHODS In a r and omized , double-blind trial , we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism . Eligible patients had right ventricular dysfunction on echocardiography or computed tomography , as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation ( or collapse ) within 7 days after r and omization . The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after r and omization . RESULTS Of 1006 patients who underwent r and omization , 1005 were included in the intention-to-treat analysis . Death or hemodynamic decompensation occurred in 13 of 506 patients ( 2.6 % ) in the tenecteplase group as compared with 28 of 499 ( 5.6 % ) in the placebo group ( odds ratio , 0.44 ; 95 % confidence interval , 0.23 to 0.87 ; P=0.02 ) . Between r and omization and day 7 , a total of 6 patients ( 1.2 % ) in the tenecteplase group and 9 ( 1.8 % ) in the placebo group died ( P=0.42 ) . Extracranial bleeding occurred in 32 patients ( 6.3 % ) in the tenecteplase group and 6 patients ( 1.2 % ) in the placebo group ( P<0.001 ) . Stroke occurred in 12 patients ( 2.4 % ) in the tenecteplase group and was hemorrhagic in 10 patients ; 1 patient ( 0.2 % ) in the placebo group had a stroke , which was hemorrhagic ( P=0.003 ) . By day 30 , a total of 12 patients ( 2.4 % ) in the tenecteplase group and 16 patients ( 3.2 % ) in the placebo group had died ( P=0.42 ) . CONCLUSIONS In patients with intermediate-risk pulmonary embolism , fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke . ( Funded by the Programme Hospitalier de Recherche Clinique in France and others ; PEITHO EudraCT number , 2006 - 005328 - 18 ; Clinical Trials.gov number , NCT00639743 . ) OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials Abstract Background : The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism ( PTE ) remains controversial . We , therefore , conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE . Methods : We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock . The patients were r and omly assigned in a single-blind fashion to receive an anticoagulant [ Enoxaparin ( 1 mg/kg twice a day ) ] plus a thrombolytic [ Alteplase ( 100 mg ) or Streptokinase ( 1500000 u/2 hours ) ] or an anticoagulant [ Enoxaparin ( 1 mg/kg twice a day ) ] alone . The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment . The secondary endpoints of the study were major bleeding , pulmonary hypertension , right ventricular dilatation at the end of the first week , and exertional dyspnea at the end of the first month . Results : Of 50 patients enrolled , 25 patients were r and omly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone . The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group ( p value = 0.022 ) . At the time of discharge , pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group ( p value = 0.018 ) ; however , reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups . There was no significant difference regarding the New York Heat Association ( NYHA ) functional class between the two groups at the end of the first month ( p value = 0.213 ) . No fatal bleeding or cerebral bleeding occurred in the patients receiving an anticoagulant plus a thrombolytic . Conclusion : When given in conjunction with anticoagulants , thrombolytics may improve the clinical course of stable patients who have acute submassive pulmonary embolism and prevent clinical deterioration The role of low-dose thrombolysis in the reduction of pulmonary artery pressure in moderate pulmonary embolism ( PE ) has not been investigated . Because the lungs are very sensitive to thrombolysis , we postulated that effective and safe thrombolysis might be achieved by a lower dose of tissue plasminogen activator . The purpose of the present study was to evaluate the role of this " safe dose " thrombolysis in the reduction of pulmonary artery pressure in moderate PE . During a 22-month period , 121 patients with moderate PE were r and omized to receive a " safe dose " of tissue plasminogen activator plus anticoagulation ( thrombolysis group [ TG ] , n = 61 patients ) or anticoagulation alone ( control group [ CG ] , n = 60 ) . The primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months . Pulmonary hypertension and the composite end point developed in 9 of 58 patients ( 16 % ) in the TG and 32 of 56 patients ( 57 % ) in the CG ( p < 0.001 ) and 9 of 58 patients ( 16 % ) in the TG and 35 of 56 patients ( 63 % ) in the CG ( p < 0.001 ) , respectively . The secondary end points were total mortality , the duration of hospital stay , bleeding at the index hospitalization , recurrent PE , and the combination of mortality and recurrent PE . The duration of hospitalization was 2.2 ± 0.5 days in the TG and 4.9 ± 0.8 days in the CG ( p < 0.001 ) . The combination of death plus recurrent PE was 1 ( 1.6 % ) in TG and 6 ( 10 % ) in the CG ( p = 0.0489 ) . No bleeding occurred in any group , and despite a positive trend in favor of a " safe dose " thrombolysis , no significant difference was noted in the rate of individual outcomes of death and recurrent PE when assessed independently . In conclusion , the results from the present prospect i ve r and omized trial suggests that " safe dose " thrombolysis is safe and effective in the treatment of moderate PE , with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months BACKGROUND The influence of the duration of anticoagulant therapy after venous thromboembolism ( VTE ) on the long-term morbidity and mortality is unclear . AIM To investigate the long-term sequelae of VTE in patients r and omized to different duration of secondary prophylaxis . METHODS In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months , we extended the originally planned 2 years follow-up to 10 years . The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome ( PTS ) was performed . Recurrent thromboembolism was adjudicated by a radiologist , blinded to treatment allocation . Causes of death were obtained from the Swedish Death Registry . RESULTS Of the 897 patients r and omized , 545 could be evaluated at the 10 years follow-up . The probability of developing severe PTS was 6 % and any sign of PTS was seen in 56.3 % of the evaluated patients . In multivariate analysis , old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years . Recurrent thromboembolism occurred in 29.1 % of the patients with a higher rate among males , older patients , those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge , proximal deep vein thrombosis , or pulmonary embolism . Death occurred in 28.5 % , which was a higher mortality than expected with a st and ardized incidence ratio ( SIR ) of 1.43 ( 95 % CI 1.28 - 1.58 ) , mainly because of a higher mortality than expected from cancer ( SIR 1.83 ; 95 % CI 1.44 - 2.23 ) or from myocardial infa rct ion or stroke ( SIR 1.28 ; 95 % CI 1.00 - 1.56 ) . The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes . CONCLUSION The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months . A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed BACKGROUND The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms . OBJECTIVES The aim of this r and omized , open trial was to evaluate the efficacy and safety of alteplase followed by heparin , versus heparin alone , in 36 patients with angiographically documented pulmonary embolism . METHODS Twenty patients were allocated r and omly to a 2-h infusion of alteplase ( 10 mg bolus , then 90 mg over 2 h ) followed by heparin ; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h . RESULTS The vascular obstruction , assessed by the Miller index at pulmonary angiography , decreased significantly in alteplase-treated patients ( p less than 0.01 ) from a baseline of 28.3 + /- 2.9 to a value of 24.8 + /- 5.2 2 h after the start of infusion ; in the heparin group there was no change ( from 25.3 + /- 5.3 to 25.2 + /- 5.4 ) . Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 + /- 7.8 mm Hg to 21.4 + /- 6.7 in the alteplase group and increased in the heparin group ( from 22.3 + /- 10.5 to 24.8 + /- 11.2 mm Hg ) . For a subset of patients , lung scans were performed at baseline and on days 7 and 30 . There were no differences between the two groups in the follow-up lung scans , but there were significant decreases from the baseline values . Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group ( p = NS ) . There were three major bleeding episodes in the alteplase group and two in the heparin group . Two patients died after fibrinolysis ( one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage ) and one patient in the heparin group died of recurrent pulmonary embolism . CONCLUSIONS Alteplase result ed in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin . However , the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Twenty patients with clinical signs of deep vein thrombosis of a duration not exceeding 72 hours , and with the condition confirmed phlebographically , were r and omly allocated to one of two groups in a double-blind study . In group 1 the patients received urokinase in a low-dose regimen of 200 000 Ploug units during the first 24 hours , followed by infusion of heparin , 40 000 units daily during the next 5 days . Patients in group 2 received heparin only , 40 000 units daily for 6 days . The clinical course was assessed daily . When the infusion period was completed , the phlebography was repeated , and the results of the two examinations were compared with respect to extent of filling defects and the degree of non-filling of the deep veins . We found no superiority in the regimen consisting of urokinase preceding heparin infusion , compared with that of heparin infusion alone . Most of the patients improved clinical ly during the 6-day infusion period , but the degree of thrombosis , evaluated phlebographically , was unaltered or even deteriorated during the period in all patients except two . Overt bleeding was noted in 6 patients BACKGROUND Conventional anticoagulant treatment for acute deep vein thrombosis ( DVT ) effectively prevents thrombus extension and recurrence , but does not dissolve the clot , and many patients develop post-thrombotic syndrome ( PTS ) . We aim ed to examine whether additional treatment with catheter-directed thrombolysis ( CDT ) using alteplase reduced development of PTS . METHODS Participants in this open-label , r and omised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region . Patients aged 18 - 75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset . Patients were r and omly assigned ( 1:1 ) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT . R and omisation was stratified for involvement of the pelvic veins with blocks of six . We assessed two co- primary outcomes : frequency of PTS as assessed by Villalta score at 24 months , and iliofemoral patency after 6 months . Analyses were by intention to treat . This trial is registered at Clinical Trials.gov , NCT00251771 . FINDINGS 209 patients were r and omly assigned to treatment groups ( 108 control , 101 CDT ) . At completion of 24 months ' follow-up , data for clinical status were available for 189 patients ( 90 % ; 99 control , 90 CDT ) . At 24 months , 37 ( 41·1 % , 95 % CI 31·5 - 51·4 ) patients allocated additional CDT presented with PTS compared with 55 ( 55·6 % , 95 % CI 45·7 - 65·0 ) in the control group ( p=0·047 ) . The difference in PTS corresponds to an absolute risk reduction of 14·4 % ( 95 % CI 0·2 - 27·9 ) , and the number needed to treat was 7 ( 95 % CI 4 - 502 ) . Iliofemoral patency after 6 months was reported in 58 patients ( 65·9 % , 95 % CI 55·5 - 75·0 ) on CDT versus 45 ( 47·4 % , 37·6 - 57·3 ) on control ( p=0·012 ) . 20 bleeding complications related to CDT included three major and five clinical ly relevant bleeds . INTERPRETATION Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding . FUNDING South-Eastern Norway Regional Health Authority ; Research Council of Norway ; University of Oslo ; Oslo University Hospital OBJECTIVE catheter directed thrombolysis has been advocated for complete and rapid dissolution of iliofemoral deep venous thrombosis ( DVT ) . The aim of our study is to compare , in a r and omised trial , local thrombolysis and anticoagulation with anticoagulation alone in patients with iliofemoral DVT . METHODS a consecutive series of 35 eligible patients , were r and omised to either catheter directed thrombolysis followed by anticoagulation or to anticoagulation alone . Clot lysis and deep venous reflux were assessed with ultrasound duplex and plethysmography after 6 months . RESULTS complete data were available in the 18 and 17 patients r and omised to thrombolysis and anticoagulation , respectively . At 6 months , patency rate was better in cases treated with thrombolysis [ 13/18 ( 72 % ) vs 2/17 ( 12 % ) , p < 0.001 ] . Venous reflux was higher in- patients treated with anticoagulant [ 7 patients ( 41 % ) vs 2 ( 11 % ) , p = 0.04 ] . CONCLUSION in the short-term patients treated with catheter directed thrombolysis obtained better patency and competence than those treated with st and ard anticoagulation Bolus urokinase ( Abbokinase ) is effective for initial treatment of deep venous thrombosis but is associated with a high rate of rigors . This r and omized controlled trial was undertaken among patients with deep venous thrombosis to evaluate the efficacy and safety of a novel thrombolytic agent , recombinant urokinase ( rUK ) , administered as three bolus infusions of 1 million U over a 24-hour period versus heparin alone . Of 361 patients with DVT screened , 17 ( 5 % ) were enrolled . Recent surgery was the most common reason for exclusion ( n = 113 , 31 % ) . Images of the patients were obtained at baseline , 24 to 48 hours after r and omization , and before hospital discharge . Two patients in each treatment group had minor clot progression . One patient in the heparin group had no change ; all other patients showed mild ( < 50 % ; n = 5 in each group ) or moderate ( > 50 % ; n = 1 in each group ) improvement . No bleeding complications or rigors developed in patients r and omized to rUK . Mean bleeding times among patients given rUK were not significantly different from mean values of patients given heparin at any of the measured time points available for comparison ( 331 vs 387 seconds at baseline and 381 vs 416 seconds at 24 hours ) . However , mean fibrinogen levels declined with successive urokinase boluses and were significantly lower than levels in patients treated with heparin at 24 ( 233 mg/dl vs 466 mg/dl , p = 0.01 ) and 48 hours ( 270 mg/dl vs 474 mg/dl , p = 0.02 ) . Although bolus rUK had a favorable safety profile , rUK was no more effective than heparin in achieving clot lysis at the doses used in this trial INTRODUCTION The clinical benefit of thrombolytic treatment over heparin in patients with pulmonary embolism without hemodynamic compromise remains controversial . In these patients bolus tenecteplase has the potential to provide an effective and safe thrombolysis . METHODS We evaluated the effect of tenecteplase on right ventricle dysfunction ( RVD ) assessed by echocardiography in hemodynamically stable patients with PE in a multicenter , r and omized , double-blind , placebo-controlled study . RVD was defined as right/left ventricle end-diastolic dimension ratio > 1 in the apical 4-chamber view . Patients were r and omized to receive weight-adjusted single-bolus tenecteplase or placebo . All patients received unfractionated heparin . Reduction of RVD at 24 hours was the primary efficacy end-point and was evaluated by an independent committee unaware of treatment allocation . RESULTS Overall , 58 patients were r and omized . Echocardiograms were adequate for efficacy analysis in 51 patients , 23 r and omized to tenecteplase and 28 to placebo . The reduction of right to left ventricle end-diastolic dimension ratio at 24 hours was 0.31+/-0.08 in patients r and omized to tenecteplase as compared to 0.10+/-0.07 in patients r and omized to placebo ( p=0.04 ) . One patient r and omized to tenecteplase suffered a clinical event ( recurrent pulmonary embolism ) in comparison to three patients r and omized to placebo ( 1 recurrent pulmonary embolism ; 1 clinical deterioration and 1 non pulmonary embolism-related death ) . Two non fatal major bleedings occurred with tenecteplase ( 1 intracranial ) and one with placebo . CONCLUSION In hemodynamically stable patients with PE , treatment with single bolus tenecteplase is feasible at the same dosages used for acute myocardial infa rct ion and is associated with reduction of RVD at 24 hours . Whether this benefit is associated with an improved clinical outcome without excessive bleeding is currently explored in a large clinical trial IMPORTANCE The role of catheter-directed thrombolysis ( CDT ) in the treatment of acute proximal deep vein thrombosis ( DVT ) is controversial , and the nationwide safety outcomes are unknown . OBJECTIVES The primary objective was to compare in-hospital outcomes of CDT plus anticoagulation with those of anticoagulation alone . The secondary objective was to evaluate the temporal trends in the utilization and outcomes of CDT in the treatment of proximal DVT . DESIGN , SETTING , AND PARTICIPANTS Observational study of patients with a principal discharge diagnosis of proximal or caval DVT from 2005 to 2010 in the Nationwide Inpatient Sample ( NIS ) data base . We compared patients treated with CDT plus anticoagulation with the patients treated with anticoagulation alone . We used propensity scores to construct 2 matched groups of 3594 patients in each group for comparative outcomes analysis . MAIN OUTCOMES AND MEASURES The primary study outcome was in-hospital mortality . The secondary outcomes included bleeding complications , length of stay , and hospital charges . RESULTS Among a total of 90,618 patients hospitalized for DVT ( national estimate of 449,200 hospitalizations ) , 3649 ( 4.1 % ) underwent CDT . The CDT utilization rates increased from 2.3 % in 2005 to 5.9 % in 2010 . Based on the propensity-matched comparison , the in-hospital mortality was not significantly different between the CDT and the anticoagulation groups ( 1.2 % vs 0.9 % ) ( OR , 1.40 [ 95 % CI , 0.88 - 2.25 ] ) ( P = .15 ) . The rates of blood transfusion ( 11.1 % vs 6.5 % ) ( OR , 1.85 [ 95 % CI , 1.57 - 2.20 ] ) ( P < .001 ) , pulmonary embolism ( 17.9 % vs 11.4 % ) ( OR , 1.69 [ 95 % CI , 1.49 - 1.94 ] ) ( P < .001 ) , intracranial hemorrhage ( 0.9 % vs 0.3 % ) ( OR , 2.72 [ 95 % CI , 1.40 - 5.30 ] ) ( P = .03 ) , and vena cava filter placement ( 34.8 % vs 15.6 % ) ( OR , 2.89 [ 95 % CI , 2.58 - 3.23 ] ) ( P < .001 ) were significantly higher in the CDT group . The CDT group had longer mean ( SD ) length of stay ( 7.2 [ 5.8 ] vs 5.0 [ 4.7 ] days ) ( OR , 2.27 [ 95 % CI , 1.49 - 1.94 ] ) ( P < .001 ) and higher hospital charges ( $ 85,094 [ $ 69,121 ] vs $ 28,164 [ $ 42,067 ] ) ( P < .001 ) compared with the anticoagulation group . CONCLUSIONS AND RELEVANCE In this study , we did not find any difference in the mortality between the CDT and the anticoagulation groups , but evidence of higher adverse events was noted in the CDT group . In the context of this observational data and continued improvements in technology , a r and omized trial with outcomes such as mortality and postthrombotic syndrome is needed to definitively address this comparative effectiveness A controlled , prospect i ve study comparing streptokinase and heparin treatment has been completed in 51 patients presenting with acute proximal venous thrombosis of less than 8 days ' clinical duration . Patients were studied by means of pre‐treatment , post‐treatment , 3‐ and 12‐monthly phlebography and pulmonary perfusion scanning and were followed up at 3‐monthly intervals PURPOSE To compare the efficacy and safety of recombinant human tissue-type plasminogen activator ( rt-PA , supplied as Activase ) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis ( DVT ) of the leg . PATIENTS AND METHODS Sixty-four patients underwent 65 r and omizations to rt-PA alone ( n = 36 ) , rt-PA plus heparin ( n = 17 ) , or heparin alone ( n = 12 ) in a prospect i ve , multicenter , r and omized , open-label trial , with efficacy assessed by a radiology panel unaware of treatment assignment . Patients r and omly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein , with a maximum dose of 150 mg . All patients then received heparin and warfarin for the remainder of the hospitalization . Follow-up venography was performed 24 to 36 hours after initiation of therapy . RESULTS Complete or more than 50 % lysis occurred in 10 ( 28 % ) patients treated with rt-PA , five ( 29 % ) patients with rt-PA plus heparin , and no patient treated with heparin . No lysis occurred in 16 ( 44 % ) patients treated with rt-PA plus heparin , and 10 ( 83 % ) patients who received heparin alone ( p = 0.04 ) . There was one major complication , a nonfatal intracranial hemorrhage in a patient who received rt-PA alone . At 7 to 10 days after initiation of treatment , the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients , including those assigned to receive heparin alone . CONCLUSION ( 1 ) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone ; ( 2 ) the addition of heparin to rt-PA does not improve the lysis rate ; ( 3 ) DVT treated with heparin is commonly associated with a rise in the transaminase level ; ( 4 ) heparin does not increase the risk of bleeding from rt-PA therapy ; and ( 5 ) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT OBJECTIVES The goal of this study was to assess the short- and long-term efficacy of different thrombolytic therapy regimens in patients with leg or pelvic deep venous thrombosis ( DVT ) . BACKGROUND It is unclear whether locoregional or systemic thrombolysis is superior in treating acute leg DVT or even whether lysis is more effective than anticoagulation therapy in preventing postthrombotic syndrome . METHODS A total of 250 patients averaging 40 years of age with acute DVT were r and omized into five groups to receive full heparinization ( 1,000 IU/h ) and compression treatment , with four groups also administered locoregional tissue plasminogen activator ( 20 mg/day ) or urokinase ( 100,000 IU/day ) or systemic streptokinase ( 3,000,000 IU daily ) or urokinase ( 5,000,000 IU daily ) . All groups then received anticoagulation and compression treatment for one year . Primary efficacy criteria included the change after one year in the number of closed vein segments and the occurrence of postthrombotic syndrome . RESULTS Systemic thrombolytic therapy significantly reduced the number of closed vein segments after 12 months in patients with acute DVT compared with conventional treatment ( p < 0.05 ) . Postthrombotic syndrome also occurred with less frequency in systemically treated patients versus controls ( p < 0.001 ) . High-dose thrombolysis led to better rates of complete recanalization after seven days ( p < 0.01 ) than locoregional lysis . However , 12 patients receiving thrombolysis ( 9 systemic , 3 local ) suffered major bleeding complications ; 9 patients on systemic treatment developed pulmonary emboli . CONCLUSIONS Systemic thrombolytic treatment for acute DVT achieved a significantly better short- and long-term clinical outcome than conventional heparin/anticoagulation therapy but at the expense of a serious increase in major bleeding and pulmonary emboli . Given the inherent risks for such serious complications , systemic thrombolysis , although effective , should be used selectively in limb-threatening thrombotic situations To test the efficacy of thrombolytic therapy in massive pulmonary embolism , we conducted a prospect i ve r and omized controlled trial . Eight patients were r and omized to receive either 1,500,000 IU of streptokinase in 1 hour through a peripheral vein followed by heparin or heparin alone . All patients had major risk factors for deep vein thrombosis ( DVT ) and were considered to have high clinical suspicion for pulmonary embolism ( PE ) . At baseline all patients had a similar degree of systemic arterial hypotension , pulmonary arterial hypertension , and right ventricular dysfunction . The time of onset of cardiogenic shock in both groups was comparable ( 2.25 ±0.5 hours in the streptokinase group and 1.75 ±0.96 hours in the heparin group ) . The four patients who were r and omized to streptokinase improved in the first hour after treatment , survived , and in 2 years of follow-up are without pulmonary arterial hypertension . All four patients treated with heparin alone died from 1 to 3 hours after arrival at the emergency room ( p=0.02 ) . Post-thrombolytic therapy the diagnosis of PE was sustained in the streptokinase group by high probability V/Q lung scans and proven DVT . A necropsy study performed in three patients in the heparin group showed massive pulmonary embolism and right ventricular myocardial infa rct ion , without significant coronary arterial obstruction . The results indicate that thrombolytic therapy reduces the mortality rate of massive acute pulmonary embolism BACKGROUND The reason some patients with deep venous thrombosis ( DVT ) develop the postthrombotic syndrome is not well understood . OBJECTIVE To determine the frequency , time course , and predictors of the postthrombotic syndrome after acute DVT . DESIGN Prospect i ve , multicenter cohort study . SETTING 8 Canadian hospital centers . PATIENTS 387 out patients and in patients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004 . MEASUREMENTS St and ardized assessment s for the postthrombotic syndrome using the Villalta scale at 1 , 4 , 8 , 12 , and 24 months after enrollment . Mean postthrombotic score and severity category at each interval was calculated . Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling . RESULTS At all study intervals , about 30 % of patients had mild ( score , 5 to 9 ) , 10 % had moderate ( score , 10 to 14 ) , and 3 % had severe ( score > 14 or ulcer ) postthrombotic syndrome . Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up ( 1.97 , 5.03 , and 7.00 increase in Villalta score for mild , moderate , and severe 1-month severity categories , respectively , vs. none ; P < 0.001 ) . Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein ( 2.23 increase in score vs. distal [ calf ] venous thrombosis ; P < 0.001 ) , higher body mass index ( 0.14 increase in score per kg/m(2 ) ; P < 0.001 ) , previous ipsilateral venous thrombosis ( 1.78 increase in score ; P = 0.001 ) , older age ( 0.30 increase in score per 10-year age increase ; P = 0.011 ) , and female sex ( 0.79 increase in score ; P = 0.020 ) . LIMITATIONS Decisions to prescribe compression stockings were left to treating physicians rather than by protocol . Because international normalized ratio data were unavailable , the relationship between anticoagulation quality and Villalta scores could not be assessed . CONCLUSION The postthrombotic syndrome occurs frequently after DVT . Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes Experiments in animals have demonstrated that recombinant tissue plasminogen activator ( rt-PA ) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated , and bleeding is reduced when rt-PA is administered over a short period . In previous studies in patients with thrombotic disease , rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours . To determine whether a short course regimen of rt-PA can achieve thrombolysis , a double-blind r and omized trial has been conducted in which patients with objective ly established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg ( 33 patients ) or saline placebo ( 25 patients ) . Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post- study drug administration . Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients ( p = 0.026 ) . At 24 hours , the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group ( p = 0.017 ) . By day 7 , no difference in lung scan resolution was detected between the groups . There were no major bleeds in either group nor were there any differences in transfusion requirements between groups . Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites . These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism Treatment with streptokinase or heparin was allocated r and omly to 20 patients with major pulmonary embolism verified by angiography . In addition , 4 patients treated with streptokinase and 1 patient treated with heparin were included in the trial prior to the start of treatment . Streptokinase of heparin was given for 72 hours and pulmonary angiography was repeated . The angiographic evidence of thrombolysis was significantly greater ( p less than 0.01 ) in the 14 patients treated with streptokinase than in the 11 treated with heparin . In the heparin group , 1 patient died from massive embolism 15 hours after the start of treatment . In another patient who died 4 weeks later from cerebral glibolastoma , persistent massive embolism contributed to the fatal outcome . In the streptokinase group , 1 patient with a metastatic pulmonary carcinoma died 3 weeks after the start of treatment from gangrene of both legs following thrombotic occlusion of the inferior vena cava . Bleeding was more common after treatment with streptokinase than with heparin , but was not a serious problem in any patient . It is concluded that patients with life-threatening pulmonary embolism should be offered the benefits of streptokinase Background St and ard treatment for deep vein thrombosis aims to reduce immediate complications . Use of thrombolysis or clot dissolving drugs could reduce the long-term complications of post-thrombotic syndrome ( PTS ) including pain , swelling , skin discolouration , or venous ulceration in the affected leg . This is the third up date of a review first published in 2004 . Objectives To assess the effects of thrombolytic therapy and anticoagulation compared to anticoagulation alone for the management of people with acute deep vein thrombosis ( DVT ) of the lower limb as determined by the effects on pulmonary embolism , recurrent venous thromboembolism , major bleeding , post-thrombotic complications , venous patency and venous function . Search methods For this up date the Cochrane Vascular Information Specialist ( CIS ) search ed the Specialised Register ( February 2016 ) . In addition the CIS search ed the Cochrane Register of Studies ( CENTRAL ( 2016 , Issue 1 ) ) . Trial registries were search ed for details of ongoing or unpublished studies . Selection criteria R and omised controlled trials ( RCTs ) examining thrombolysis and anticoagulation versus anticoagulation for acute DVT were considered . Data collection and analysis For this up date ( 2016 ) , LW and CB selected trials , extracted data independently , and sought advice from MPA where necessary . We assessed study quality with the Cochrane risk of bias tool . For dichotomous outcomes , we calculated the risk ratio ( RR ) and corresponding 95 % confidence interval ( CI ) . Data were pooled using a fixed-effect model unless significant heterogeneity was identified in which case a r and om-effects model was used . GRADE was used to assess the overall quality of the evidence supporting the outcomes assessed in this review . Main results Seventeen RCTs with 1103 participants were included . These studies differed in the both thrombolytic agent used and in the technique used to deliver it . Systemic , loco-regional and catheter-directed thrombolysis ( CDT ) were all included . Fourteen studies were rated as low risk of bias and three studies were rated as high risk of bias . We combined the results as any ( all ) thrombolysis compared to st and ard anticoagulation . Complete clot lysis occurred significantly more often in the treatment group at early follow-up ( RR 4.91 ; 95 % CI 1.66 to 14.53 , P = 0.004 ) and at intermediate follow-up ( RR 2.44 ; 95 % CI 1.40 to 4.27 , P = 0.002 ; moderate quality evidence ) . A similar effect was seen for any degree of improvement in venous patency . Up to five years after treatment significantly less PTS occurred in those receiving thrombolysis ( RR 0.66 , 95 % CI 0.53 to 0.81 ; P < 0.0001 ; moderate quality evidence ) . This reduction in PTS was still observed at late follow-up ( beyond five years ) , in two studies ( RR 0.58 , 95 % CI 0.45 to 0.77 ; P < 0.0001 ; moderate quality evidence ) . Leg ulceration was reduced although the data were limited by small numbers ( RR 0.87 ; 95 % CI 0.16 to 4.73 , P = 0.87 ) . Those receiving thrombolysis had increased bleeding complications ( RR 2.23 ; 95 % CI 1.41 to 3.52 , P = 0.0006 ; moderate quality evidence ) . Three strokes occurred in the treatment group , all in trials conducted pre-1990 , and none in the control group . There was no significant effect on mortality detected at either early or intermediate follow-up . Data on the occurrence of pulmonary embolism ( PE ) and recurrent DVT were inconclusive . Systemic thrombolysis and CDT had similar levels of effectiveness . Studies of CDT included two trials in femoral and iliofemoral DVT , and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion . Authors ' conclusions Thrombolysis increases the patency of veins and reduces the incidence of PTS following proximal DVT by a third . Evidence suggests that systemic administration and CDT have similar effectiveness . Strict eligibility criteria appears to improve safety in recent studies and may be necessary to reduce the risk of bleeding complications . This may limit the applicability of this treatment . In those who are treated there is a small increased risk of bleeding . Using GRADE assessment , the evidence was judged to be of moderate quality due to many trials having low numbers of participants . However , the results across studies were consistent and we have reasonable confidence in these results A technique of quantitative venography has been developed in which values are assigned to the deep veins of the calf , knee , thigh , and pelvis , based upon the calculated volume and degree of occlusion of these venous segments . A maximum score of 40 units reflects complete thrombosis of all segments . This technique has been applied to a r and omized , single-blind study of streptokinase versus heparin treatment . Each group of 12 patients had similar mean inital venographic scores ; follow-up venograms were performed 5 days after the start of therapy . Streptokinase patients with high initial scores ( larger than 20 ) showed a mean improvement of 12.1 units , while those with low initial scores(less than 20 ) were essentially unchanged . Heparin patients with high scores had a minimal mean improvement of 1.1 units , but those with low scores had a significant mean extension of thrombosis of 8.6 units . Patients with symptoms for less than 7 days showed greated mean improvement ( 12.7 units ) with streptokinase that those with a longer duration of symptoms ( 2.0 units ) ; heparin patients in these subgroups showed a mean worsening of 7.5 units and no change , respectively . Extrinsic venous obstruction by tumor did not prevent an excellent response to streptokinase . No single test of coagulation of fibriolysis was a reliable indicator of the degree of venographic response to lytic therapy . Pyrexia and hemorrhagic complications occurred in over one-half of the streptokinase patients ; one had an anaphylactic reaction , and one died of intracerebral hemorrhage during therapy . The data suggest that lytic therapy is best restricted to the patient with acute extensive thrombosis . Also , continuous infusions of heparin according to current guidelines may be inadequate to prevent thrombus growth in some patients A prospect i ve r and omized study was performed to investigate the long-term sequelae of calf vein thrombosis ( CVT ) and correlate them to the success of the initial treatment . Thirty-six patients with symptomatic CVT , verified by venography , were treated with heparin or low-dose streptokinase ( SK ) combined with low-dose heparin . Venography was repeated after 1 week , and long-term follow-up was performed clinical ly and with foot volumetry after an average of 5 years . Since the low-dose SK regimen led to serious hemorrhagic side-effects in a parallel study , the present investigation was discontinued prematurely . The thrombolysis achieved was greater with SK but , since the initial thrombi were somewhat larger in this group , no significant difference in the average size of the thrombi after therapy could be displayed between the groups . The long-term sequelae and results of foot volumetry were also equal . Signs or symptoms of venous insufficiency were found in 37 % , and foot volumetry showed deep venous insufficiency in 26 % of the cases . There was a correlation between the hemodynamic change , as assessed by foot volumetry , and the venographic severity . This relation was stronger for the size of the thrombus after treatment than for the initial size . Thus , it seems important to limit the extent of a CVT in order to minimize the long-term sequelae , but administration of SK is not justified due to side-effects OBJECTIVE To investigate the therapeutic efficacy of anticoagulation(AC ) and its combination with catheter-directed thrombolysis(CDT ) for deep venous thrombosis of lower extremities . METHODS One hundred and thirty-nine patients with deep venous thrombosis of early lower extremities treated in our hospital from May 2011 to September 2013 were selected and r and omly divided into the AC group(n= 66 ) and CDT+AC group(n= 73 ) . The thrombolytic effects , adverse reactions , post-thrombotic syndrome ( PTS ) and quality of life were evaluated . RESULTS There were no serious adverse events during treatment and after treatment in the 2 groups . Hematomas in 2 cases and gross hematuria in 3 cases were observed in the CDT+AC group . The gums bleed or gross hematuria in 3 cases were observed in the AC group . Compared with the AC group , the number of grade I thrombolysis in CDT+AC group decreased significantly ( 60.61 % vs 9.59%)(P < 0.05 ) , and the number of grade III thrombolysis increased significantly(7.57 % vs 49.31%)(P < 0.05 ) . During follow-up , the incidence of PTS in both groups showed increase year by year , and none of the patients had severe PTS . The incidence PTS in CDT+AC group at 12 months and 18 months were lower than those of AC group(17.81 % vs 33.33 % , 24.66 % vs 43.94%)(P < 0.05 ) . Compared with the AC group , the scores of physiological role and vitality in CDT+AC group at 6 months , 12 months and 18 months were higher ( P < 0.05 ) . CONCLUSION Catheter-directed thrombolysis combined with AC therapy can promote the mitigation of clinical symptoms in patients with DVT of lower extremities and is beneficial to promoting the life quality of patients In a prospect i ve trial , 42 medical patients with a history of deep vein thrombosis of less than five days were allocated at r and om to treatment with streptokinase or heparin . Only patients with extensive thromboses were included . Streptokinase was given in a loading dose of 250 000 IU and a maintenance dose of 100 000 IU/hour for 4 days as a mean . Heparin was given in a loading dose of 15 000 IU and a maintenance dose of 20 000 - 50 000 IU/day . The therapeutic results were evaluated by phlebography . Significant thrombolysis occurred in 71.4 % of 21 patients treated with streptokinase and in 23.8 % of the 21 heparin-treated patients . Using the chi2-test for overall association , this difference was statistically highly significant ( p = 0.002 ) . Three patients in each treatment group experienced major bleeding , two in each group requiring blood transfusions . Minor bleeding and slight rise in temperature were encountered more often in the streptokinase than in the heparin group . It is concluded that patients with acute deep vein thrombosis with proximal extension of the thrombus beyond the calf veins should be offered a therapeutic trial with streptokinase Twenty-seven patients with deep vein thrombosis whose primary therapy was r and omized between streptokinase and heparin were reevaluated clinical ly and by ascending venography after a mean period of 7 months . Normal venograms were found in 6 ( 40 % ) of the streptokinase-treated patients and in 1 patient ( 8 % ) who had heparin therapy . Segmental valve preservation was found in 1 patient from each group . All patients with complete or partial valve preservation became asymptomatic . Vein re canalization without preservation of valves occurred in 18 patients : 8 ( 54 % ) of those on streptokinase , and 10 ( 83 % ) of those on heparin . At the time of follow-up , 11 of these 18 patients , including 8 who had had prior thrombosis , reported peripheral edema ; the postphlebitic syndrome devel oped in 1 . Factors favoring a good outcome of acute venous thrombosis were ( 1 ) no prior thrombotic disease , ( 2 ) localized thrombosis , and ( 3 ) prompt streptokinase therapy Patients with symptoms of deep vein thrombosis for less than 10 days were treated with a st and ard dose of heparin . In the open label phase of the trial , 11 patients received 100 mg rt-PA on the first day and 50 mg on the subsequent day in an 8 hour infusion . In the double-blind phase , 8 patients were r and omized to the same rt-PA regimen , 6 patients to an infusion of 50 mg rt-PA over 8 hours on days 1 and 2 , and 7 patients to placebo infusions . The mean change in venographic score in all patients treated with rt-PA plus heparin is -3.8 units compared to -0.6 units in patients treated with heparin alone ( p = 0.06 ) . Bleeding complications classified as major were noted in 8/25 patients receiving the combined treatment BACKGROUND The aim of the following prospect i ve study was to investigate whether patients benefited from locoregional lysis treatment of recent deep leg vein thrombosis after 1 year . PATIENTS AND METHODS The prospect i ve study included 69 patients aged between 22 and 58 years , in whom recent lower leg vein and popliteal vein thromboses were diagnosed by phlebography . Patients were r and omized to one of three treatment groups : one group was treated for a maximum of 7 days with full heparinization and daily dose of 20 mg rt-PA administered locoregionally over a period of 4 hours ; a second group received 100,000 IU/h urokinase locoregionally for a maximum of 7 days , in addition to full heparinization ; and in the third group ( control group ) , intravenous heparin infusions after PTT constituted the only form of treatment . All patients were given phenprocoumon from day 7 and received compression treatment . Before treatment began and before the course of phenprocoumon started , phlebography and colour duplex sonography examinations were carried out . After 12 months , follow-up duplex sonography was conducted to evaluate the reflux times over the popliteal vein and the degree of patency of the deep leg veins . RESULTS Complete lysis was achieved in 6 of 22 patients in the recombinant tissue plasminogen activator ( rt-PA ) group and in 11 of 22 patients in the urokinase group . At follow-up examination after 12 months , there were serious post-thrombotic changes in 14 of 22 patients in the rt-PA group , in 9 of 22 patients in the urokinase group and in 15 of 22 patients in the group of patients who received no lysis treatment . CONCLUSION Patients with recently formed thromboses in the lower leg and popliteal veins who underwent 7 days of locoregional lysis treatment with urokinase demonstrated significantly fewer clinical symptoms of post-thrombotic syndrome after 1 year than those who received locoregional treatment with rt-PA over a similar period or a control group treated with anticoagulants only Thirty patients with deep vein thrombosis of the legs of less than four days ' duration were allocated at r and om to treatment with heparin , streptokinase , or Arvin under laboratory control . When the fate of the thrombi was assessed by objective techniques — phlebography and the 125I-labelled fibrinogen test — the incidence of complete thrombolysis was greatest in the streptokinase group . Complications arose during treatment in each group but were least with Arvin . The natural history of the disease favours clinical but not always anatomical recovery Data from a non-r and omised study have hinted that in patients with acute pulmonary embolism ( PE ) , thrombolysis followed by heparin more rapidly reverses right-ventricular dysfunction and restores pulmonary tissue perfusion than does heparin alone . We have pursued this idea in a r and omised protocol . 46 haemodynamically stable patients were r and omised to recombinant tissue plasminogen activator ( alteplase , rt-PA ) 100 mg over 2 h followed by intravenous heparin and 55 to heparin alone . Right-ventricular wall motion was assessed qualitatively , and right-ventricular end diastolic area was estimated by planimetry from echocardiograms at baseline and at 3 and 24 hours . Pulmonary perfusion scans were obtained at baseline and 24 hours . In 39 % of rt-PA patients but in only 17 % of heparin alone patients right-ventricular wall motion at 24 hours had improved from baseline and in 2 % and 17 % , respectively , it worsened ( p = 0.005 ) . rt-PA patients also had a significant decrease in right-ventricular end-diastolic area during the 24 hours after r and omisation and a significant absolute improvement in pulmonary perfusion ( 14.6 % vs 1.5 % ) . No clinical episodes of recurrent PE were noted among rt-PA patients , but there were 2 fatal and 3 non-fatal clinical ly suspected recurrent PEs within 14 days in patients r and omised to heparin alone . rt-PA rapidly improves right-ventricular function and pulmonary perfusion among patients with PE and may lead to a lower rate of adverse clinical outcomes We performed a r and omized trial comparing two dosing regimens of recombinant tissue plasminogen activator ( rt-PA ) plus heparin vs heparin alone in the treatment of acute proximal deep vein thrombosis in 83 patients . Of 12 patients who received 0.5 mg/kg rt-PA plus heparin over 4 h , seven ( 58 percent ) had greater than 50 percent lysis of the thrombus , compared with none of 12 who received placebo plus heparin ( p = 0.002 ) . Of 28 patients who received 0.5 mg/kg rt-PA over 8 h , repeated in 24 h , six ( 21 percent ) had greater than 50 percent lysis , compared with two ( 7 percent ) of 30 patients who received placebo plus heparin ( p = 0.11 ) . The 4-h infusion of rt-PA produced a 40 percent reduction and the 8-h infusion an 11 percent reduction in plasma fibrinogen concentration . At long-term follow-up , three ( 25 percent ) of 12 patients in whom greater than 50 percent lysis was achieved had symptoms of the postphlebitic syndrome , compared with 19 ( 56 percent ) of 34 patients in whom lysis was less than 50 percent ( p = 0.07 ) Objectives : To investigate the efficacy and safety of initial thrombolysis by recombinant tissue-type plasminogen activator ( rt-PA ) in compared with anticoagulant therapy in patients with acute intermediate-risk pulmonary embolism ( PE ) . Methods : Sixty-six patients with acute intermediate-risk PE were r and omly assigned to receive rt-PA or LMWH between June 2014 and June 2017 in our department . We obtained information regarding the difference in the right ventricle/left ventricle ( RV/LV ) ratio , pulmonary artery systolic pressure ( PASP ) , clinical symptoms improvement , PE-related mortality , hemodynamic decompensation , recurrent PE , and major and minor bleeding . Results : In the rt-PA group , the mean PASP was reduced from 52.0±12.2 at baseline to 34.8±9.4 ( p<0.001 ) and the mean RV/LV ratio was reduced from 1.26±0.22 at baseline to 0.96±0.18 ( p<0.001 ) at 24 hours . In the LMWH group , the mean PASP was 53.4±12.8 at baseline and 48.5±11.9 at 24 hours ( p=0.11 ) , and the mean RV/LV ratio was 1.22±0.19 at baseline and 1.17±0.21 at 24 hours ( p=0.31 ) . In comparison with the LMWH group , there was a significant reduction in PASP and an improvement in the symptom severity in the rt-PA group . At 90 days , there was no difference in mortality , recurrent venous thromboembolism and major bleeding as a safety outcome , but increased minor bleeding and decreased hemodynamic decompensation occurred in the rt-PA group . Conclusions : In patients with acute intermediate-risk PE , low dose thrombolytic therapy is considered safe and effective , it can be recommended as an alternative option in clinical treatment Background The post‐thrombotic syndrome frequently develops in patients with proximal deep‐vein thrombosis despite treatment with anticoagulant therapy . Pharmacomechanical catheter‐directed thrombolysis ( hereafter “ pharmacomechanical thrombolysis ” ) rapidly removes thrombus and is hypothesized to reduce the risk of the post‐thrombotic syndrome . Methods We r and omly assigned 692 patients with acute proximal deep‐vein thrombosis to receive either anticoagulation alone ( control group ) or anticoagulation plus pharmacomechanical thrombolysis ( catheter‐mediated or device‐mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration , with or without stenting ) . The primary outcome was development of the post‐thrombotic syndrome between 6 and 24 months of follow‐up . Results Between 6 and 24 months , there was no significant between‐group difference in the percentage of patients with the post‐thrombotic syndrome ( 47 % in the pharmacomechanical‐thrombolysis group and 48 % in the control group ; risk ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.82 to 1.11 ; P=0.56 ) . Pharmacomechanical thrombolysis led to more major bleeding events within 10 days ( 1.7 % vs. 0.3 % of patients , P=0.049 ) , but no significant difference in recurrent venous thromboembolism was seen over the 24‐month follow‐up period ( 12 % in the pharmacomechanical‐thrombolysis group and 8 % in the control group , P=0.09 ) . Moderate‐to‐severe post‐thrombotic syndrome occurred in 18 % of patients in the pharmacomechanical‐thrombolysis group versus 24 % of those in the control group ( risk ratio , 0.73 ; 95 % CI , 0.54 to 0.98 ; P=0.04 ) . Severity scores for the post‐thrombotic syndrome were lower in the pharmacomechanical‐thrombolysis group than in the control group at 6 , 12 , 18 , and 24 months of follow‐up ( P<0.01 for the comparison of the Villalta scores at each time point ) , but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups . Conclusions Among patients with acute proximal deep‐vein thrombosis , the addition of pharmacomechanical catheter‐directed thrombolysis to anticoagulation did not result in a lower risk of the post‐thrombotic syndrome but did result in a higher risk of major bleeding . ( Funded by the National Heart , Lung , and Blood Institute and others ; ATTRACT Clinical Trials.gov number , NCT00790335 . Introduction : The aim of this study was to assess the effect of thrombolysis versus heparin treatment on echocardiographic parameters and clinical outcome , during hospitalization and within the first 180 days after admission , in patients with first episode of submassive pulmonary embolism ( SPE ) and right ventricle dysfunction ( RVD ) . Methods : Consecutive patients ( age , 18–75 years ) with a first episode of SPE , symptoms onset since no more than 6 hours , normal blood pressure ( > 100 mm Hg ) , echocardiographic evidence of RVD and positive lung spiral computed tomography were double-blind r and omized : 1 group received 100 mg of alteplase ( 10-mg bolus , followed by a 90-mg intravenous infusion over a period of 2 hours ) , while the other group received matching placebo . In addition to alteplase or placebo , both groups received an unfractionated heparin treatment . Echocardiogram was performed at admission , at 24 , 48 and 72 hours , at discharge and at 3 and at 6 months after r and omization . Results : Seventy-two patients were included into the study ; 37 were assigned to thrombolysis and 35 to placebo . Both groups were well matched with regard to features and clinical presentation . Thrombolysis group showed a significant early improvement of RV function compared with heparin group , and this improvement was observed also during the follow-up ( 180 days ) . The same group also showed significant reduction in clinical events during the hospitalization and follow-up . Conclusions : Our data suggest that , in hemodynamically stable patients with SPE , thrombolysis shows an earliest reduction of RVD and a more favorable trend in clinical outcome , so , it could merit consideration in SPE Background — In patients with acute pulmonary embolism , systemic thrombolysis improves right ventricular ( RV ) dilatation , is associated with major bleeding , and is withheld in many patients at risk . This multicenter r and omized , controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis ( USAT ) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients . Methods and Results — Fifty-nine patients ( 63±14 years ) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension ( RV/LV ) ratio ≥1.0 were r and omized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours ( n=30 ; USAT group ) or unfractionated heparin alone ( n=29 ; heparin group ) . Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours . Safety outcomes included death , major and minor bleeding , and recurrent venous thromboembolism at 90 days . In the USAT group , the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours ( P<0.001 ) ; in the heparin group , mean RV/LV ratios were 1.20±0.14 and 1.17±0.20 , respectively ( P=0.31 ) . The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 ( P<0.001 ) , respectively . At 90 days , there was 1 death ( in the heparin group ) , no major bleeding , 4 minor bleeding episodes ( 3 in the USAT group and 1 in the heparin group ; P=0.61 ) , and no recurrent venous thromboembolism . Conclusions — In patients with pulmonary embolism at intermediate risk , a st and ardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours , without an increase in bleeding complications . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01166997 |
2,399 | 18,194,527 | Conclusion It is feasible to systematic ally develop theoretically-based interventions to change professional practice . | Background Evidence shows that antibiotics have limited effectiveness in the management of upper respiratory tract infection ( URTI ) yet GPs continue to prescribe antibiotics .
Implementation research does not currently provide a strong evidence base to guide the choice of interventions to promote the uptake of such evidence -based practice by health professionals .
While systematic review s demonstrate that interventions to change clinical practice can be effective , heterogeneity between studies hinders generalisation to routine practice .
Psychological models of behaviour change that have been used successfully to predict variation in behaviour in the general population can also predict the clinical behaviour of healthcare professionals .
The purpose of this study was to design two theoretically-based interventions to promote the management of upper respiratory tract infection ( URTI ) without prescribing antibiotics . | Background Psychological theories of behaviour may provide a framework to guide the design of interventions to change professional behaviour . Behaviour change interventions , design ed using psychological theory and targeting important motivational beliefs , were experimentally evaluated for effects on the behavioural intention and simulated behaviour of GPs in the management of uncomplicated upper respiratory tract infection ( URTI ) . Methods The design was a 2 × 2 factorial r and omised controlled trial . A postal question naire was developed based on three theories of human behaviour : Theory of Planned Behaviour ; Social Cognitive Theory and Operant Learning Theory . The beliefs and attitudes of GPs regarding the management of URTI without antibiotics and rates of prescribing on eight patient scenarios were measured at baseline and post-intervention . Two theory-based interventions , a " grade d task " with " action planning " and a " persuasive communication " , were incorporated into the post-intervention question naire . Trial groups were compared using co-variate analyses . Results Post-intervention question naires were returned for 340/397 ( 86 % ) GPs who responded to the baseline survey . Each intervention had a significant effect on its targeted behavioural belief : compared to those not receiving the intervention GPs completing Intervention 1 reported stronger self-efficacy scores ( Beta = 1.41 , 95 % CI : 0.64 to 2.25 ) and GPs completing Intervention 2 had more positive anticipated consequences scores ( Beta = 0.98 , 95 % CI = 0.46 to 1.98 ) . Intervention 2 had a significant effect on intention ( Beta = 0.90 , 95 % CI = 0.41 to 1.38 ) and simulated behaviour ( Beta = 0.47 , 95 % CI = 0.19 to 0.74 ) . Conclusion GPs ' intended management of URTI was significantly influenced by their confidence in their ability to manage URTI without antibiotics and the consequences they anticipated as a result of doing so . Two targeted behaviour change interventions differentially affected these beliefs . One intervention also significantly enhanced GPs ' intentions not to prescribe antibiotics for URTI and result ed in lower rates of prescribing on patient scenarios compared to a control group . The theoretical frameworks utilised provide a scientific rationale for underst and ing how and why the interventions had these effects , improving the reproducibility and generalisability of these findings and offering a sound basis for an intervention in a " real world " trial . Trial registration Clinical trials.gov BACKGROUND Suspected acute viral upper respiratory tract infection ( SAVURTI ) is the commonest acute reason why children consult in general practice . The clinical course varies widely and about one in five children re-consult for the same SAVURTI episode . If clinicians had feasible tools for predicting which children are likely to suffer a prolonged course , then additional explanations and possibly treatments could be provided at the initial consultation that might enable carers to manage the condition without re-consulting . OBJECTIVE To identify features available on the day of consulting that might predict a prolonged clinical course among children with SAVURTI . METHOD Regression analysis using Canadian Respiratory Illness and Flu Scale ( CARIFS ) data from a r and omized controlled trial cohort of children aged from 6 months to 12 years consulting in general practice with SAVURTI . RESULTS Two variables from the clinician 's records ( ' age ' and ' cough ' ) and two variables from the CARIFS completed by carers on the day of consulting ( ' fever ' and ' low energy , tired ' ) explained approximately 15 % of the variation present in CARIFS scores on day seven . CONCLUSION Children and carers may benefit from a clear account of the evidence that the clinical course of RTIs in children varies widely and may be longer that expected , and that prediction for individuals is difficult Background Biomedical research constantly produces new findings , but these are not routinely incorporated into health care practice . Currently , a range of interventions to promote the uptake of emerging evidence are available . While their effectiveness has been tested in pragmatic trials , these do not form a basis from which to generalise to routine care setting s. Implementation research is the scientific study of methods to promote the uptake of research findings , and hence to reduce inappropriate care . As clinical practice is a form of human behaviour , theories of human behaviour that have proved to be useful in other setting s offer a basis for developing a scientific rationale for the choice of interventions . Aims The aims of this protocol are 1 ) to develop interventions to change beliefs that have already been identified as antecedents to antibiotic prescribing for sore throats , and 2 ) to experimentally evaluate these interventions to identify those that have the largest impact on behavioural intention and behavioural simulation . Design The clinical focus for this work will be the management of uncomplicated sore throat in general practice . Symptoms of upper respiratory tract infections are common presenting features in primary care . They are frequently treated with antibiotics , and research evidence is clear that antibiotic treatment offers little or no benefit to otherwise healthy adult patients .Reducing antibiotic prescribing in the community by the " prudent " use of antibiotics is seen as one way to slow the rise in antibiotic resistance , and appears safe , at least in children . However , our underst and ing of how to do this is limited . Participants will be general medical practitioners . Two theory-based interventions will be design ed to address the discriminant beliefs in the prescribing of antibiotics for sore throat , using empirically derived re sources . The interventions will be evaluated in a 2 × 2 factorial r and omised controlled trial delivered in a postal question naire survey . Two outcome measures will be assessed : behavioural intention and behavioural simulation Little is known about incorporation of new knowledge from r and omised clinical trials into clinical practice . Thrombolytic therapy was shown to reduce the mortality of acute myocardial infa rct ion in several large trials published during 1986 - 88 . To examine the effect of these data on clinical practice , we analysed the supply of thrombolytic drugs in a representative English region ( population 4.7 million ) in 1987 - 92 . During the study period there were over 10,000 hospital admissions per year in the region for acute myocardial infa rct ion . From a very low initial level , thrombolytic drug use rose slowly for several years after publication of the trial results and reached a plateau in 1991 - 92 . Rates of use per 1000 patients admitted with myocardial infa rct ion varied almost six-fold between districts in 1989 - 90 and over two-fold in 1991 - 92 . Level of use attained by districts in the latter period was strongly associated with the extent of their previous participation in multicentre trials of thrombolysis ( p = 0.003 ) ; we estimate that 35 - 50 % of patients admitted with acute myocardial infa rct ion were receiving thrombolytics . The full potential of thrombolytic treatment has still not been achieved in routine care and the limiting factors need to be defined Background Psychological models can be used to underst and and predict behaviour in a wide range of setting s. However , they have not been consistently applied to health professional behaviours , and the contribution of differing theories is not clear . The aim of this study was to explore the usefulness of a range of psychological theories to predict health professional behaviour relating to management of upper respiratory tract infections ( URTIs ) without antibiotics . Methods Psychological measures were collected by postal question naire survey from a r and om sample of general practitioners ( GPs ) in Scotl and . The outcome measures were clinical behaviour ( using antibiotic prescription rates as a proxy indicator ) , behavioural simulation ( scenario-based decisions to managing URTI with or without antibiotics ) and behavioural intention ( general intention to managing URTI without antibiotics ) . Explanatory variables were the constructs within the following theories : Theory of Planned Behaviour ( TPB ) , Social Cognitive Theory ( SCT ) , Common Sense Self-Regulation Model ( CS-SRM ) , Operant Learning Theory ( OLT ) , Implementation Intention ( II ) , Stage Model ( SM ) , and knowledge ( a non-theoretical construct ) . For each outcome measure , multiple regression analysis was used to examine the predictive value of each theoretical model individually . Following this ' theory level ' analysis , a ' cross theory ' analysis was conducted to investigate the combined predictive value of all significant individual constructs across theories . Results All theories were tested , but only significant results are presented . When predicting behaviour , at the theory level , OLT explained 6 % of the variance and , in a cross theory analysis , OLT ' evidence of habitual behaviour ' also explained 6 % . When predicting behavioural simulation , at the theory level , the proportion of variance explained was : TPB , 31 % ; SCT , 26 % ; II , 6 % ; OLT , 24 % . GPs who reported having already decided to change their management to try to avoid the use of antibiotics made significantly fewer scenario-based decisions to prescribe . In the cross theory analysis , perceived behavioural control ( TPB ) , evidence of habitual behaviour ( OLT ) , CS-SRM cause ( chance/bad luck ) , and intention entered the equation , together explaining 36 % of the variance . When predicting intention , at the theory level , the proportion of variance explained was : TPB , 30 % ; SCT , 29 % ; CS-SRM 27 % ; OLT , 43 % . GPs who reported that they had already decided to change their management to try to avoid the use of antibiotics had a significantly higher intention to manage URTIs without prescribing antibiotics . In the cross theory analysis , OLT evidence of habitual behaviour , TPB attitudes , risk perception , CS-SRM control by doctor , TPB perceived behavioural control and CS-SRM control by treatment entered the equation , together explaining 49 % of the variance in intention . Conclusion The study provides evidence that psychological models can be useful in underst and ing and predicting clinical behaviour . Taking a theory-based approach enables the creation of a replicable methodology for identifying factors that predict clinical behaviour . However , a number of conceptual and method ological challenges remain OBJECTIVES : General practitioners ( GPs ) in the UK continue to prescribe antibiotics for patients with sore throats despite evidence that they are ineffective and can contribute to the growth of antibiotic resistance in the population . This study uses the theory of planned behaviour ( TPB ) to investigate the strength of intention to prescribe antibiotics , and to identify the salient beliefs associated with this intention . DESIGN : Cross-sectional study testing hypotheses derived from the TPB . METHOD : A 66-item postal question naire was distributed to a r and om sample of GPs in one NHS region ( N = 185 ) . The question naire included measures of intention to prescribe antibiotics , attitude , behavioural beliefs and evaluations , normative beliefs and evaluations , perceived behavioural control , control beliefs , and past prescribing . RESULTS : Two-thirds of the GPs returned complete question naires ( N = 126 , 68 % ) . The majority intended to prescribe antibiotics for less than half of their patients with sore throats ( N = 69 , 55 % ) . The variables specified in TPB predicted 48 % of the variance in intention , with past behaviour adding a further 15 % . Seven salient beliefs distinguished between doctors who intend to prescribe antibiotics and those who do not . CONCLUSIONS : Attitudes towards antibiotics and control beliefs are important predictors of intention to prescribe , as predicted by TPB . Interventions could target salient beliefs associated with motivation to prescribe A consistent finding in health services research is the report of uneven uptake of research findings . Implementation trials have a variable record of success in effectively influencing clinicians ' behaviour . A more systematic approach may be to conduct Intervention Modelling Experiments before service-level trials , examining intervention effects on ' interim endpoints ' representing clinical behaviour , derived from empirically supported psychological theories . The objectives were to : ( 1 ) Design Intervention Modelling Experiments by backward engineering a ' real-world ' r and omised controlled trial ( NEXUS ) ; ( 2 ) examine the applicability of psychological theories to clinical decision-making ; ( 3 ) explore whether psychological theories can illuminate how interventions achieve their effects . A 2 x 2 factorial r and omised controlled trial was design ed with pre- and post-intervention data collection by postal question naire surveys . The first survey was used to generate feedback data and the interventions were delivered in the second survey . General medical practitioners ( GPs ) in Engl and and Scotl and participated . First survey respondents were r and omised twice to receive or not audit and feedback and educational reminder messages . The main outcome measures included behavioural intention ( general plan to refer for lumbar X-rays ) and simulated behaviour ( specific , scenario-based , decisions to refer for lumbar X-ray ) . Predictors were attitude , subjective norm , perceived behavioural control ( theory of planned behaviour ) , self-efficacy ( social cognitive theory ) and decision difficulty . Both interventions significantly influenced simulated behaviour , but neither influenced behavioural intention . There were no interaction effects . All theoretically derived cognitions significantly predicted simulated behaviour . Only subjective norm was not predictive of behavioural intention . The effect of audit and feedback on simulated behaviour was mediated through perceived behavioural control . The results of this study suggest that Intervention Modelling Experiments , using psychological models to help isolate mediators of clinical decision-making , may be a means of developing more potent interventions , and selecting implementation interventions with a greater likelihood of success in a service-level r and omised controlled trial Objective The lag between publication of evidence for clinical practice and implementation by clinicians may be decades . Research using psychological models demonstrates that changing intention is very important in changing behaviour . This study examined an intervention ( rehearsing alternative actions ) to change dentists ' intention to implement evidence -based practice ( EBP ) for third molar ( TM ) management . Design R and omised controlled trial / postal . Setting Primary care . Subjects and methods Dentists were r and omly selected from the Scottish Dental Practice Board Register , then r and omly allocated to intervention or control groups , and sent a question naire . The intervention group listed management alternatives to TM extraction prior to their TM extraction intention , and the control group did not . Based on psychological models for reducing a behaviour 's frequency ( EBP is weighted against TM extraction ) , prior listing of alternatives should decrease extraction intention . Main outcome measure Intention to extract TMs . Results A total of 99 dentists — 70 Males , 29 Females ; mean age = 41.42 years ( SD = 8.62 ) participated in the study . The intervention significantly influenced intention to extract TMs , as desired . Despite similar background and knowledge of management alternatives , participants in the intervention group had significantly lower intention to extract : control group mean ( SD ) = 0.39 ( 1.99 ) ; intervention group mean ( SD ) = −0.78 ( 1.89 ) ; mean difference ( SE ) = 1.17 ( 0.42 ) ; 95 % confidence interval for the difference = 0.34 to 1.99 . Conclusion Results suggest this intervention , which successfully influenced a proximal predictor of behaviour pertinent to dental EBP , may result in improved EBP in a service-level trial . Basing implementation interventions and trial methodology on psychological models may effectively bridge the gap between clinical guidelines and practice OBJECTIVE --To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infa rct ion . DESIGN -- Prospect i ve postal question naire survey of a r and om one in two sample of general practitioners in the region . SETTING --The nine family practitioner committee areas within the Northern Regional Health Authority . PATIENTS -- Patients who had had a myocardial infa rct ion and were discharged to their general practitioner . MAIN OUTCOME MEASURE -- Whether beta blockers or aspirin , or both , were given on discharge . RESULTS --Of 267 patients , 158 ( 59 % ) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication . For most patients this entailed underuse of one drug , but 17 ( 6 % ) of patients received no treatment . beta Blockers were 2.5 times less likely to be used than aspirin . Treatment was not associated with the age or sex of the patient , risk of further infa rct ion , or hospital of discharge . CONCLUSIONS -- Secondary prophylaxis after myocardial infa rct ion is practised haphazardly . It should be offered to all patients who can tolerate it , after a trial period to assess any side effects of the drugs if necessary OBJECTIVE To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes . DATA SOURCES MEDLINE , SCI SEARCH , CINAHL and the Research and Development Re source Base in CME were search ed for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive . STUDY SELECTION Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed r and om or quasi-r and om allocation methods in their study design s to assign individual subjects or groups . Interventions included such activities as conferences , outreach visits , the use of local opinion leaders , audit and feedback , and reminder systems . DATA EXTRACTION Details extracted from the studies included the study design ; the unit of allocation ( e.g. , patient , provider , practice , hospital ) ; the characteristics of the targeted health care professionals , educational interventions and patients ( when appropriate ) ; and the main outcome measure . DATA SYNTHESIS The inclusion criteria were met by 102 trials . Areas of behaviour change included general patient management , preventive services , prescribing practice s , treatment of specific conditions such as hypertension or diabetes , and diagnostic service or hospital utilization . Dissemination-only strategies , such as conferences or the mailing of unsolicited material s , demonstrated little or no changes in health professional behaviour or health outcome when used alone . More complex interventions , such as the use of outreach visits or local opinion leaders , ranged from ineffective to highly effective but were most often moderately effective ( result ing in reductions of 20 % to 50 % in the incidence of inappropriate performance ) . CONCLUSION There are no " magic bullets " for improving the quality of health care , but there are a wide range of interventions available that , if used appropriately , could lead to important improvements in professional practice and patient outcomes |
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